Richard Zare
Marguerite Blake Wilbur Professor of Natural Science and Professor, by courtesy, of Physics
Chemistry
Bio
A pioneer in the use of lasers to study chemical reactions at the molecular level, Marguerite Blake Wilbur Professor Richard N. Zare pursues diverse theoretical and experimental interests in physical chemistry and nanoscale chemical analysis. The Zarelab has made a broad impact in analytic chemistry with development of laser-induced fluorescence to study reaction dynamics, and seminal contributions to understanding of molecular collision processes. The group continues to invent tools and measurement techniques to study phenomena from reaction in microdroplets to drug delivery.
Born in 1939 in Cleveland, Ohio, Professor Zare trained in physical and analytical chemistry at Harvard University (B.A. 1961, Ph.D. 1964). His doctoral study under Professor Dudley Herschbach explored photodissociation dynamics. After faculty positions spanning chemistry at the Massachusetts Institute of Technology, chemistry, physics and astrophysics at the University of Colorado, and chemistry at Columbia University, he joined the Stanford chemistry faculty in 1977. He has taught an introductory chemistry class every year since. As a Howard Hughes Medical Institute Professor since 2006, Professor Zare has also developed a course introducing undergraduates to hands-on interdisciplinary research, combining physics, and biology to explore how living systems use molecular interactions with light for vision, photosynthesis and more. Professor Zare served as chair of the Department of Chemistry from 2005 to 2011, and has helped to guide scientific policy as chairman of several national and international science boards. His dedication to research and teaching has been recognized in many awards, including the National Medal of Science, the Wolf Prize in Chemistry, and the Presidential Award for Excellence in Science, Mathematics, and Engineering Mentoring. Among other honors, Professor Zare is a member of the National Academy of Sciences, the American Academy of Arts and Sciences, and the American Philosophical Society. He has also received 11 honorary doctorates.
Current research in the Zarelab explores wide-ranging questions in physical and analytical chemistry, from the study of elementary chemical reactions to chemical analysis of extraterrestrial materials. The major focus of these efforts is chemical analysis on the nanoscale. The team has devised tools and techniques to examine molecules in extremely tiny volumes – the volumes characteristic of what is found in heterogeneous structures in mineral samples or in the contents of cells and subcellular compartments. Group members have also made contributions to the chemical analysis of liquid samples separated using a capillary format by electrophoresis or electrochromatography. Some “firsts” include the use of cavity ring-down spectroscopy to analyze trace species in solution, development of detectors for capillary electrophoresis based on the techniques of laser-induced fluorescence, and CCD imaging, and the use of mass spectrometric imaging of tissue samples by means of desorption electrospray ionization.
Please visit the Zarelab website to learn more: http://web.stanford.edu/group/Zarelab/
Academic Appointments
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Professor, Chemistry
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Professor (By courtesy), Physics
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Member, Bio-X
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Member, Cardiovascular Institute
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Member, Stanford Cancer Institute
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Affiliate, Stanford Woods Institute for the Environment
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Member, Wu Tsai Neurosciences Institute
Administrative Appointments
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Chair, Department of Chemistry, Stanford University (2006 - 2011)
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Howard Hughes Medical Institute Professor, Stanford University (2006 - 2010)
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Professor of Physics, Stanford University (1992 - Present)
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Marguerite Blake Wilbur Professor in Natural Science, Stanford University (1987 - Present)
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Fellow Adjoint, Joint Institute for Laboratory Astrophysics, University of Colorado (1985 - Present)
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Stanford University Fellow, Stanford University (1984 - 1986)
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Christensen Fellow, St. Catherine's College, Oxford University (1982 - 1982)
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Shell Distinguished Professor of Chemistry, Stanford University (1980 - 1985)
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Professor, Department of Chemistry, Stanford University (1977 - Present)
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Higgins Professor of Natural Science, Columbia University (1975 - 1977)
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Professor, Department of Chemistry, Columbia University (1969 - 1977)
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Associate Professor, Department of Physics and Astrophysics and Department of Chemistry, University of Colorado (1968 - 1969)
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Assistant Professor, Department of Physics and Astrophysics, University of Colorado (1966 - 1968)
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Assistant Professor, Department of Chemistry, Massachusetts Institute of Technology (1965 - 1966)
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Postdoctoral Research Associate, Joint Institute for Laboratory Astrophysics (JILA), University of Colorado (1964 - 1965)
Honors & Awards
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National Medal of Science, National Science Foundation (1983)
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Wolf Prize in Chemistry, Wolf Foundation, Israel (2005)
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BBVA Foundation Frontiers of Knowledge Award in the Basic Sciences category, BBVA Foundation (2010)
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King Faisal International Prize in Science, King Faisal Foundation (2011)
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Presidential Award for Excellence in Science, Mathematics, and Engineering Mentoring (PAESMEM), U.S. Office of Science and Technology Policy (2009)
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The Welch Award in Chemistry, The Welch Foundation (1999)
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National Academy of Sciences Award in Chemical Sciences, National Academy of Sciences (1991)
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American Chemical Society Award in Analytical Chemistry, American Chemical Society (1998)
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Irving Langmuir Prize, American Physical Society (1985)
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Peter Debye Award in Physical Chemistry, American Chemical Society (1991)
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George C. Pimentel Award in Chemical Education, American Chemical Society (2008)
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Priestley Medal, American Chemical Society (2010)
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Honorary Doctorate, University of South Florida (2013)
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The International Science and Technology Cooperation Award, The People's Republic of China (2012)
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The World Academy of Sciences Lecture Medal, World Academy of Arts and Sciences (2012)
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The Torbern Bergman Medal, The Swedish Chemical Society, The Analytical Division (2012)
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Honorary Membership, Japan Society for Analytical Chemistry (JSAC) (2011)
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Einstein Professorship, Chinese Academy of Sciences (2011)
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R. B. Bernstein Award in Stereodynamics, International Symposium on Stereodynamics of Chemical Reactions (2010)
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Honorary Fellow, Chinese Chemical Society (2010)
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Theodore William Richards Medal, Northeastern Section of the American Chemical Society (2010)
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F. A. Cotton Medal for Excellence in Chemical Research, Texas A&M University, Department of Chemistry, and Texas A&M Section, American Chemical Society (2009)
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H. Julian Allen Award, NASA Ames Research Center (2007)
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Dudley R. Herschbach Award, Dynamics of Molecular Collisions Meeting, Santa Fe, New Mexico (2007)
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Honorary Doctorate, Chalmers Institute of Technology (2007)
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Oesper Award, University of Cincinnati and Cincinnati Section of the American Chemical Society (2006)
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Chandler Medal, Department of Chemistry, Columbia University (2005)
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Pupin Medal "for service to the nation", Columbia University School of Engineering (2005)
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Nichols Medal, New York Section of the American Chemical Society (2005)
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James Flack Norris Award for Outstanding Achievement in the Teaching of Chemistry, Northeastern Section of the American Chemical Society (2004)
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Laurance and Naomi Carpenter Hoagland Prize for Excellence in Undergraduate Education, Stanford University (2003)
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Honorary Doctorate, Université Paul Sabatier, Toulouse, France (2003)
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Distinguished Chemist Award, American Chemical Society Sierra Nevada Section (2002)
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Honorary Doctorate, Hunan University (2002)
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Scientific Achievement Award, California Separation Science Society (CaSSS) (2000 - 2001)
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Madison Marshall Award, American Chemical Society, North Alabama (2000)
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Honorary Doctorate, D Univ, The University of York (2001)
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Honorary Doctorate, State University of West Georgia (2001)
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Faraday Medal & Lectureship, Royal Society of Chemistry (2001)
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Charles Lathrop Parsons Award, American Chemical Society (2001)
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Nobel Laureate Signature Award for Graduate Education, American Chemical Society (2000)
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Arthur L. Schawlow Prize in Laser Science, American Physical Society (2000)
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Doctor of Philosophy, honoris causa, Uppsala University (2000)
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Doctor of Science, honoris causa, Columbia University (1999)
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E. Bright Wilson Award in Spectroscopy, The American Chemical Society (1999)
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Distinguished Service Award, National Science Board (1998)
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Centennial Medal, Graduate School of Arts and Sciences, Harvard University (1998)
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G. M. Kosalapoff Award, Auburn Section, American Chemical Society (1998)
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Eastern Analytical Symposium Award for Outstanding Achievements in the Field of Analytical Chemistry, Eastern Analytical Symposium (1997)
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Allan V. Cox Medal for Faculty Excellence Fostering Undergraduate Research, Stanford University (1997)
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NASA Exceptional Scientific Achievement Award, NASA (1997)
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Phi Beta Delta (Honorary Member), Phi Beta Delta (1997)
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California Scientist of the Year, California Science Center (1997)
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The Bing Fellowship Award, Stanford University (1996)
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ACS Division of Analytical Chemistry Award in Chemical Instrumentation, ACS Division of Analytical Chemistry (1995)
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Dannie-Heineman Preis, Akademie der Wissenschaften zu Göttingen (1993)
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Doctor of Science, Honorary Degree, Eidgenössische Technische Hochschule Zürich (1993)
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The Pauling Award, Puget Sound, Oregon and Portland Sections of the American Chemical Society (1993)
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The Harvey Prize, Technion, Israel Institute of Technology (1993)
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Doctor of Science, Honorary Degree, Northwestern University (1993)
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Willard Gibbs Medal, Chicago Section, American Chemical Society (1990)
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Doctor of Science, Honorary Degree, University of Arizona (1990)
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ISCO Award for Significant Contributions to Instrumentation for Biochemical Separations, International Stem Cell Corporation (ISCO) (1990)
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Dean's Award for Excellence in Teaching, Stanford University (1987)
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Kirkwood Award Medal, Yale University, New Haven Section of the American Chemical Society (1986)
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Michelson-Morley Award, Case Institute of Technology, Case Western Reserve University (1986)
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Harrison Howe Award, Rochester Section, American Chemical Society (1985)
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Remsen Award, Maryland Section, American Chemical Society (1985)
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Evans Award, The Ohio State University (1984)
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Spectroscopy Society of Pittsburgh Award, Spectroscopy Society of Pittsburgh (1983)
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Earle K. Plyler Prize, American Physical Society (1981)
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Michael Polanyi Medal, The Royal Society of Chemistry (1979)
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Fresenius Award, Phi Lambda Upsilon Honorary Chemical Society (1974)
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Alfred P. Sloan Fellowship, Alfred P. Sloan Foundation (1967 - 1969)
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Phi Beta Kappa award, Phi Beta Kappa Society (1961)
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Honorary Professor, Nanjing University
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Honorary Professor, Xiamen University
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Honorary Professor, Tsinghua University
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Honorary Professor, Dalian Institute of Chemical Physics
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Honorary Professor, University of Science and Technology of China
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Honorary Professor, Beijing Institute of Technology
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Honorary Professor, Institute of Chemistry Chinese Academy of Sciences
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Honorary Professor, Zeijiang University
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Honorary Professor, China Central Normal University
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Honorary Professor, Hunan University
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Honorary Professor, Changchun Institute of Applied Chemistry
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Honorary Professor, Shanghai Jiao Tong University
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Phillip W. West Lecture, Louisiana State University (2014)
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Pegram Lectures, Brookhaven National Laboratory, Upton, New York (2014)
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Fred M. Weissman Lecture in Analytical Chemistry, University of South Carolina, Columbia, South Carolina (2014)
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Wilhelm Jost Memorial Lectures, Freie Universität; Gottfried Wilhelm Leibniz Universität; Georg-August-Universität, Germany (2014)
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Centenary Lecture, Indian Institute of Science (IISc), Bangalore, India (2014)
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CV Raman Lecture, Indian Association for the Cultivation of Science (IACS), Kolkata, India (2014)
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Homi Bhabha Lecture, Tata Institute for Fundamental Research (TIFR), Mumbai, India (2014)
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Heaven and Earth Distinguished Lectures, Nanjing University, China (2013)
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James S. Plant Distinguished Lecture, Hamilton College, Clinton, New York (2013)
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Plenary Lecture, Wu Chien-Shiung Science Summer Camp, Xitou, Taiwan (2013)
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New Biology Distinguished Lecture, DGIST, Daegu, South Korea (2013)
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Jackson Lecture, University of Florida, Gainesville, Florida (2013)
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Martin Lecture, University of South Florida, Tampa, Florida (2013)
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Svedberg Lecture, Uppsala University, Uppsala, Sweden (2013)
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Linnett Visiting Professor Lectureship, Department of Chemistry, University of Cambridge, Cambridge, UK (2013)
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Lady Margaret Lecture, Christ's College, University of Cambridge, Cambridge, UK (2013)
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Department of Chemical Engineering, Tsinghua University, Beijing, China (2013)
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Department of Chemistry, Beijing Institute of Technology, Beijing, China (2013)
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Shipley Lecture, Department of Chemistry, Clarkson University (2013)
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Teickmann Lecture, SUNY Buffalo (2013)
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Bangalore Science Forum, Bangalore, India (2014)
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Visva-Bhrati University, Santiniketan, India (2014)
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King Abdullah University of Science and Technology (KAUST), Saudi Arabia (2014)
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ISIC Seminar, Ecole Polytechnique Fédérale de Lausaunne, Switzerland (2012)
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Jean Dreyfus Boissevain Lecture,, Bucknell University, Lewisburg, PA (2012)
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Izatt-Christensen Lecturer, Bringham Young University (2012)
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Plenary Lecture, Celebration of Chemistry, IITK, Indian Institute of Technology Kanpur (2011)
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Plenary Lecture, The Third Asian Spectroscopy Conference, Science and Art Center, Xiamen Uninversity (2011)
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Wynne-Jones Memorial Lecture, University of Newcastle (2011)
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Plenary Lecture, IUPAC International Congress on Chemical Sciences, Kyoto, Japan (2011)
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Salomon Bochner Lecture, Scientia,, Rice University (2011)
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The Thirtieth Annual Barnett Lectureship, Northeastern, The Barnett Institute of Chemical and Biological Analysis (2011)
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Distinguished Lecture Series in Mathematical and Physical Sciences, National Science Foundation (2011)
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22nd Annual Frontiers in Chemistry Symposium, The Scripps Research Institute (2011)
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Plenary Lecture, Year of Chemistry, Uppsala University (2011)
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Wolf Prize Foundation Laureate Lecture, International Symposium "Frontiers in Photon Science", University of Manchester (2010)
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Plenary Lecture, 45º Congreso Mexicano de Química y 29º Congreso Nacional de Educación, Química, Riviera Maya, Quintana Roo, Mexico (2010)
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Vail Lectures, Wake Forest University (2010)
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Plenary Lecture, International Conference on Chemical Education, Taipei, Taiwan (2010)
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Global Vision Lecture, Tsinghua University, Beijing, China (2010)
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Plenary Lecture, Chemistry Division,, Chinese Academy of Sciences, Beijing, China (2010)
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Plenary Lecture, 4th International Symposium on Bioanalysis, Changsha, China (2010)
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C. R. Mueller Memorial Lecture,, Purdue University (2010)
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Plenary Lecture, Academia Sinica, Taipei, Taiwan (2010)
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Plenary Lecture, Isranalytica, Tel Aviv, Israel (2010)
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MTSU Distinguished Lecture, Middle Tennessee State University (2009)
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NanQiang Lecture, Xiamen University, Xiamen, China (2009)
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Rajiv Gandhi Science and Technology Lecture, Bangalore, India (2009)
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Dr. Emily Davis and Dr. Homer C. Weed Lecture, Department of Chemistry and Biochemistry, University of Arizona (2009)
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A. R. Gordon Distinguished Lectures Series, University of Toronto, Toronto, Canada (2009)
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Abbott Chemistry Lectures, University of North Dakota (2009)
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Phyllis Johnson Patrick Lecture,, Kansas State University (2009)
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Platinum Jubilee Lecture, Indian Academy of Sciences, Bangalore University, Bangalore, India (2009)
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Robert S. Mulliken Lecture, University of Georgia (2008)
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Leland Wilson Endowed Lecture, University of Northern Iowa (2008)
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Frank Whitmore Lecture, The Pennsylvania State University (2008)
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Helen Murray Free Endowed Lecture, University of Wooster (2008)
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Plenary Lecture, 10th National Symposium, Chemical Research Society of India, Bangalore, India (2008)
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William A. Chupka Lectureship in Physical and Theoretical Chemistry, Yale University (2007)
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The Arnold C. Ott Lectureship in Chemistry, Grand Valley State University (2007)
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3M/Ronald A. Mitsch Lecture in Chemistry, Hamline University (2007)
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18th Leopold Marcus Lecture, Department of Chemistry, Washington University in St. Louis (2007)
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Nobel Laureates 2007 Beijing Forum on Energy and the Environment, Beijing, China (2007)
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Plenary Lecture, Ninth Annual Beckman Scholars Symposium, Irvine, California (2007)
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Roberts Lecturer, University College, London, UK (2007)
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Distinguished Frontiers Speaker, University of Toledo (2007)
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Ritter Memorial Lectures, Miami University of Ohio (2007)
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Keynote Speaker, Honors Week Celebration, Kent State University (2007)
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Morino Lectures, University of Tokyo and Kyoto University, Japan (2007)
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Plenary Speaker, New Zealand Institute of Chemistry Conference, Rotorua, New Zealand (2006)
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Sir Neil Waters Distinguished Lectureship, Massey University, Palmerston North, New Zealand (2006)
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Michael Faraday Lecture, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India (2006)
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Mission Bay Seminar, University of California at San Francisco (2006)
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Cal Giddings Lecture, University of Utah (2006)
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Keynote Lecture, Biennial Conference on Chemical Education (BCCE), Purdue University (2006)
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Plenary Lecture, International Workshop on Bioanalytical Chemistry and Biomedical Engineering, Hunan University, Changsa, China (2010)
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Distinguished Zhang Dayu Lecture, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China (2006)
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Lectures in Modern Chemistry, Department of Chemistry,, University of British Columbia, Vancouver, BC, Canada (2006)
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Spring Colloquium Speaker, Department of Chemistry & Biochemistry, University of Washington (2006)
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Frontiers in Chemical Research Lecturer, Texas A & M University (2006)
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G. Wilse Robinson Lecturer, Texas Tech University (2006)
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Vessman Lecture, Chalmers University, Göteborg, Sweden (2006)
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Plenary Speaker, Photon Science Institute Launch, University of Manchester, Manchester, UK (2006)
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Purves Lecturer, McGill University, Montreal, Canada (2005)
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Plenary Speaker, Federation of Analytical Chemistry and Spectroscopy Societies (FACCS), Quebec City, Canada (2005)
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Plenary Speaker, ScotCHEM Launch, Edinburgh, Scotland (2005)
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Plenary Speaker, CONNECT 2005, 12th Royal Australian Chemical Institute (RACI) National Convention, Sydney, Australia (2005)
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PECRUM Lecturer (Perspective on Chemistry Research), University of Michigan) (2005)
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Keynote Speaker, Atlanta Undergraduate Research Alliance (AURA) (2005)
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Arthur D. Little Lecturer, Massachusetts Institute of Technology (2004)
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William E. Mahoney Lecturer, University of Massachusetts Amherst (2004)
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Mitchum E. Warren, Jr. Lecturer, Department of Chemistry, Vanderbilt University (2004)
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Robert A. Jenkins Memorial Lecturer, Department of Chemistry, University of Wyoming (2004)
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Charles Herron Lecturer, Department of Chemistry and Biochemistry, Florida State University (2004)
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Noyes Lecturer, Department of Chemistry, University of Oregon (2004)
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Plenary Lecturer, Singapore International Chemistry Conference 3, Singapore (2003)
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S. Dexter Squibb Distinguished Lecturer, Department of Chemistry, University of North Carolina (2003)
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Haberman Lecturer, Department of Chemistry, Marquette University (2002)
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Samuel M. McElvain Seminar, Department of Chemistry, University of Wisconsin-Madison (2002)
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George Gamow Memorial Lecture, University of Colorado at Boulder (2002)
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L. Carroll King Memorial Lectures, Department of Chemistry, Northwestern University (2001)
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R. T. Majors Lecturer, Department of Chemistry, University of Connecticut (2001)
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Flygare Memorial Lecturer, Department of Chemistry, University of Illinois at Urbana-Champaign (2001)
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Hirschmann Lecturer, Oberlin College (2000)
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Carr Lecturer, Department of Chemistry, Coe College (2000)
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Manuel G. Menendez Memorial Lecturer, Department of Physics and Astronomy, University of Georgia (2000)
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Anderson Lecture, Department of Physics and Astronomy, Denison University (2000)
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The Timothy J. O’Leary, S. J. Distinguished Scientist Lecturer, Science Departments of Gonzaga University (2000)
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Lyle Ramsay Dawson Lecturer, Department of Chemistry, University of Kentucky (1999)
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S. C. Lind Lecture, East Tennessee Section of the American Chemical Society (1999)
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Charles M. Knight Lecturer, Department of Chemistry, The University of Akron (1999)
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The O. K. Rice Lecturer, Department of Chemistry, The University of North Carolina at Chapel Hill (1999)
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The Lloyd B. Thomas Chemistry Scholars Lecturer, Department of Chemistry, University of Missouri (1999)
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The Joe L. Franklin Memorial Lecture, Department of Chemistry, Rice University (1999)
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Harry Emmett Gunning Lecturer, Department of Chemistry, University of Alberta (1998)
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Clifford C. Hach Lecturer, Department of Chemistry, University of Wyoming (1998)
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Barre Lecturer, University of Montreal, Canada (1998)
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Kosalopoff Lecturer, Auburn University (1998)
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Centenary Lecturer, Royal Society of Chemistry (1998)
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Anson L. Clark Memorial Lecturer, University of Texas at Dallas (1998)
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Billings Distinguished Lecturer, Montana State University (1998)
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Claude Worthington Benedum Foundation Lecturer, West Virginia University (1997)
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Robert Maurer Lecture, Department of Physics, University of Arkansas (1997)
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Frank G. and Jean M. Chesley Lectureship, Carleton College (1997)
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Jacob Bigeleisen Endowed Lecture, State University of New York Stony Brook (1996)
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Gooch-Stephens Lectureship, Baylor University (1996)
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DuPont Distinguished Speaker, Indiana University (1996)
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G.B. Kistiakowsky Lecturer, Harvard University (1996)
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Alexander M. Cruickshank Lecturer, Gordon Research Conference (1996)
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Leroy Eyring Lecturer, Arizona State University (1995)
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Velmer Fassel Lecturer, Iowa State University (1995)
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Richard C. Lord Lecturer, Massachusetts Institute of Technology (1995)
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Fred J. Robbins Lecturer, Pomona College (1995)
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Moses Gomberg Lecturer, University of Michigan (1995)
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Lemieux Lecturer, University of Ottawa (1995)
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Frederic LeRoy Conover Memorial Lecturer, Vanderbilt University (1994)
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Raymond Lemieux Lecturer, University of Ottawa (1994)
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Peter Smith Lecturer, Duke University (1994)
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Paul C. Cross Lecturer, University of Washington (1993)
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Linus Pauling Distinguished Lecturer, Oregon State University (1993)
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R.B. Bernstein Memorial Lecturer, UCLA (1993)
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Nalbandov Lecturer, University of Illinois (1993)
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George C. Pimental Lecturer, UC Berkeley (1992)
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Robert S. Mulliken Lecturer, University of Chicago (1992)
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Arthur D. Little Lecturer, Northeastern University (1991)
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J. T. Donald Lecturer, McGill University (1991)
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Frederick Kaufman Lecturer, University of Pittsburgh (1991)
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Peter A. Leermakers Symposium Lecturer, Wesleyan University (1991)
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Russell Marker Lecturer in the Chemical Sciences, Pennsylvania State University (1991)
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Ernest H. Swift Lecturer, California Institute of Technology (1991)
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Amy/Mellon Lecturer, Purdue University (1990)
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Distinguished Scientists Lecturer, Trinity University (1990)
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E. K. C. Lee Lecturer, University of California at Irvine (1989)
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Geoffrey Frew Fellow, Australian Academy of Sciences (1989)
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Max T. Rogers Lecturer, Michigan State University (1989)
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Joel Broberg Lecturer in Chemistry, North Dakota State University (1989)
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Gustavson Lecturer, University of Denver (1989)
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Kennedy Lecturer, Washington University, St. Louis (1989)
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John Albert Southern Lecturer, Furman University (1989)
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Distinguished Visiting Lecturer, University of Texas at Austin (1989)
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Procter and Gamble Lecturer, University of Illinois at Champaign- Urbana (1988)
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Xerox Lecturer, Simon Fraser University (1988)
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Marvel-Monsanto Lecturer, University of Arizona (1988)
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Appleton Lecturer, Brown University (1988)
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Walter J. Chute Distinguished Lecturer, Dalhousie University (1987)
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Edgar Fahs Smith Lecturer, University of Pennsylvania (1987)
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Charles A. McDowell Lecturer in Chemical Physics, University of British Columbia (1987)
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Weizmann Memorial Lecturer, Weizmann Institute, Rehovot, Israel (1986)
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Friend E. Clark Lecturer, West Virginia University (1986)
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Fritz London Memorial Lecturer, Duke University (1986)
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Merck Distinguished Lecturer, Rutgers University (1986)
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"Frontiers of Science" Distinguished Visiting Professor, University of Florida (1986)
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Camille and Henry Dreyfus Lecturer, Dartmouth College (1985)
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Davis Lecturer, University of New Orleans (1985)
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Priestley Lecturer, Pennsylvania State University (1985)
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Coover Lecturer, Iowa State University (1985)
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Francis E. Blacet Lecturer, University of California at Los Angeles (1985)
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Plenary Lecturer, Lasers '84 (1984)
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John E. Willard Lecturer, University of Wisconsin (1984)
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Evans Lecturer, Ohio State University (1984)
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"Frontiers in Chemical Research" Distinguished Lecturer, Texas A&M University (1984)
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Distinguished Scientist Lecturer, University of Arizona (19983)
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ICPEAC Plenary Lecturer, XIII International Conference on the Physics of Electronic and Atomic Collisions, Berlin, Germany (1983)
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William Draper Harkins Lecturer, University of Chicago (1983)
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Falk-Plaut Lecturer, Columbia University (1983)
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Dreyfus Scholar in Residence, Hope College (1982)
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Venable Lecturer, University of North Carolina (1982)
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Albert W. Noyes Lecturer, University of Texas at Austin (1982)
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Jeremy Musher Memorial Lecturer, Hebrew University (1982)
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Guggenheim Lecturer, Reading University (1982)
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Hinschelwood Lecture, Oxford University (1982 )
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Research Scholar, Drew University (1981)
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University Professor, University of Arkansas (1981)
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Honor Lecturer in Chemistry, Arizona State University (1981)
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McGregor Lecturer, Colgate College (1980)
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Baker Lecturer, Cornell College (1980)
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Kolthoff Lecturer, University of Minnesota (1980)
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William Pyle Philips Lecturer in Chemistry, Haverford College (1980)
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Frank T. Gucker Lecturer in Chemistry, Indiana University (1979)
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Peter C. Reilly Lecturer, University of Notre Dame (1979)
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Francis Clifford Phillips Lecturer, University of Pittsburgh (1979)
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Distinguished Visiting Professor, Michigan State University (1978)
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Edward U. Condon Lecturer in Chemical Physics, University of Colorado (1977)
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Distinguished University Lecturer, University of Utah (1977)
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Sherwin Williams Lecturer, University of Illinois (1977)
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Frontiers in Chemistry Lecturer, Wayne State University (1977)
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Westinghouse Invited Lecturer in Chemistry, Pittsburgh, Pennsylvania (1976)
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Arthur D. Little Visiting Professor, Massachusetts Institute of Technology (1972)
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Harold Herborg Nielsen Lecturer, Ohio State University (1975)
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FMC Lecturer, Princeton University (1976)
Boards, Advisory Committees, Professional Organizations
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Member, Board of Trustees Committee, Stanford University (2014 - Present)
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Chair, COSEPUP (Committee on Science, Engineering, and Public Policy) of the three Academies (2012 - Present)
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Member, Advisory Board, School of New Sciences, DGIST, Daegu, South Korea (2012 - Present)
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Director of International Advisory Board, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University (2012 - Present)
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Fellow, TWAS, Academy of Sciences for the Developing World (2009 - Present)
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Fellow, American Chemical Society (2009 - Present)
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Member of the Board of Directors, Camille and Henry Dreyfus Foundation (2009 - Present)
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Honorary Fellow, Indian Academy of Sciences (2008 - Present)
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Fellow, Association for Women in Science (2008 - Present)
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Chairman, Board of Directors, Annual Reviews Inc. (1995 - Present)
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Honorary Fellow, Chemical Research Society of India (CRSI) (2007 - Present)
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Senior Presidential Advisor, Hunan University (2006 - Present)
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President, Molecular Frontiers Foundation (2006 - 2011)
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Chair, Academic Advisory Committee, Biomedical Engineering Center, Hunan University (2006 - Present)
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Member, European Academy of Sciences (2004 - Present)
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Foreign Member, Swedish Royal Academy of Engineering Sciences (IVA) (2004 - Present)
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Foreign Member, Chinese Academy of Sciences (CAS) (2004 - Present)
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Honorary Member, The World Jewish Academy of Sciences (2004 - Present)
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Honorary Fellow, Royal Society of Chemistry (2001 - Present)
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Foreign Member, Royal Society (London) (1999 - Present)
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Fellow, California Council on Science and Technology (1997 - Present)
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Honorary Fellow, California Academy of Sciences (1991 - Present)
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Fellow, Optical Society of America (1991 - Present)
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Member, American Philosophical Society (1991 - Present)
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Fellow, American Association for the Advancement of Science (1985 - Present)
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Member, National Academy of Sciences (1976 - Present)
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Member, American Academy of Arts and Sciences (1976 - Present)
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Fellow, The American Physical Society (1969 - Present)
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Non-Resident Fellow, Joint Institute of Laboratory Astrophysics (1969 - Present)
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Member, The Chemical Society (London) (1969 - Present)
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Member, Editorial Advisory Board, Angewandte Chemie
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Member, Advisory Board, DGIST (2015 - Present)
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Member, Executive Committee, Board of Directors, Wonderfest, Inc. (2011 - 2014)
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Chair, International Evaluation Committee, National Science Foundation of China (2010 - 2012)
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Fellow, Michelle R. Clayman Institute for Gender Research (2008 - 2008)
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Advisor, Camille and Henry Dreyfus Foundation (2007 - 2009)
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Faculty Affiliate, Michelle R. Clayman Institute for Gender Research (2006 - 2008)
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Foreign Council Member, Institute for Molecular Science (Japan) (1999 - 2001)
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Chairman, President’s National Medal of Science Selection Committee (1997 - 2000)
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Council Member, National Academy of Sciences (1995 - 1998)
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Member, National Science Board (1992 - 1998)
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Chairman, National Science Board (1996 - 1998)
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Chair, Commission on Physical Sciences, Mathematics, and Applications, National Research Council (1992 - 1995)
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Vice-Chair, Board of Directors, Annual Reviews, Inc. (1992 - 1995)
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Member, Government-University-Industry Research Roundtable of the National Academy of Sciences (1989 - 1992)
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Chairman, Panel on Basic Science and Technology Centers, National Academy of Sciences (1987 - 1987)
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Member, Directed Energy Weapons study panel, American Physical Society (1985 - 1987)
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Chairman, Division of Chemical Physics (DCP) American Physical Society (1985 - 1986)
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Vice-Chairman, Division of Chemical Physics (DCP), American Physical Society (1984 - 1985)
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Member, Committee on Atomic and Molecular Science (CAMS), National Research Council (1983 - 1985)
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Editor, Chemical Physics Letters (1982 - 1985)
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Chairman, National Science Foundation Advisory Panel (Chemistry Division) (1980 - 1982)
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Member, Editorial Advisory Board, Current Science (2014 - Present)
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Member, Editorial Advisory Board, Chemistry World
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Honorary Board Member, Editorial Advisory Board, Physical Chemistry and Chemical Physics (PCCP)
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Member, Editorial Advisory Board, Analytical Sciences
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Member, Editorial Advisory Board, Central European Journal of Chemistry
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Member, Editorial Advisory Board, ChemPhysChem
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Member, Editorial Advisory Board, Chemical Physics
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Member, Editorial Advisory Board, Chemical Physics Letter
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Member, Editorial Advisory Board, Molecular Physics
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Member, Editorial Advisory Board, Journal of Separation Sciences
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Member, Editorial Advisory Board, Chinese Journal of Chromatography
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Member, Editorial Advisory Board, Brainwave
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Member, Editorial Advisory Board, Chromatography
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Member, Board of Editors, The Journal of Molecular Spectroscopy
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Member, Board of Editors, Science
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Member, Board of Editors, Cambridge University Press
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Member, Board of Editors, Applied Physics
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Member, Board of Editors, Accounts of Chemical Research
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Member, Board of Editors, Analytical Chemistry
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Member, Board of Editors, Chemical & Engineering News
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Member, Board of Editors, The Journal of Chemical Physics
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Member, Board of Editors, The Journal of Physical Chemistry
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Member, Board of Editors, Optics Letters
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Member, Scientific Advisory Board, Pufendorf Institute, Lund University
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Member, International Advisory Board, State Key Laboratory of Physical Chemistry of Solid Surfaces (PCOSS)
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Member, Scientific Advisory Board, Hybrid Vigor Institute
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Member, Scientific Advisory Board, Fluidigm
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Member, Scientific Advisory Board, Eksigent, Inc.
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Member, Scientific Advisory Board, Pharmacyclics, Inc.
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Member, Scientific Advisory Board, Prolinx, Inc.
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Member, Scientific Advisory Board, Cepheid, Inc.
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Member, Scientific Advisory Board, Picarro
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Member, Scientific Advisory Board, Wonderfest
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Member, Scientific Advisory Board, Advisory Council for Chemistry at Oxford
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Member, Scientific Advisory Board, Electronic Nobel Museum/Young Scholars Program
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Member, Scientific Advisory Board, Faraday Transactions
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Member, Scientific Advisory Board, Quanta-Ray
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Member, Scientific Advisory Board, Affymax, Inc.
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Member, Scientific Advisory Board, Miller Institute
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Member, Scientific Advisory Board, IBM
Professional Education
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PhD, Harvard University (NSF Predoctoral Fellow), Chemical Physics (1964)
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Postgraduate work, University of California at Berkeley (1963)
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BA, Harvard University, Chemistry and Physics (1961)
Current Research and Scholarly Interests
My research group is exploring a variety of topics that range from the basic understanding of chemical reaction dynamics to the nature of the chemical contents of single cells.
Under thermal conditions nature seems to hide the details of how elementary reactions occur through a series of averages over reagent velocity, internal energy, impact parameter, and orientation. To discover the effects of these variables on reactivity, it is necessary to carry out studies of chemical reactions far from equilibrium in which the states of the reactants are more sharply restricted and can be varied in a controlled manner. My research group is attempting to meet this tough experimental challenge through a number of laser techniques that prepare reactants in specific quantum states and probe the quantum state distributions of the resulting products. It is our belief that such state-to-state information gives the deepest insight into the forces that operate in the breaking of old bonds and the making of new ones.
Space does not permit a full description of these projects, and I earnestly invite correspondence. The following examples are representative:
The simplest of all neutral bimolecular reactions is the exchange reaction H H2 -> H2 H. We are studying this system and various isotopic cousins using a tunable UV laser pulse to photodissociate HBr (DBr) and hence create fast H (D) atoms of known translational energy in the presence of H2 and/or D2 and using a laser multiphoton ionization time-of-flight mass spectrometer to detect the nascent molecular products in a quantum-state-specific manner by means of an imaging technique. It is expected that these product state distributions will provide a key test of the adequacy of various advanced theoretical schemes for modeling this reaction.
Analytical efforts involve the use of capillary zone electrophoresis, two-step laser desorption laser multiphoton ionization mass spectrometry, cavity ring-down spectroscopy, and Hadamard transform time-of-flight mass spectrometry. We believe these methods can revolutionize trace analysis, particularly of biomolecules in cells.
2024-25 Courses
- Chemistry in the Kitchen
CHEM 29N (Win) -
Independent Studies (6)
- Advanced Undergraduate Research
CHEM 190 (Aut, Win, Spr) - Directed Instruction/Reading
CHEM 90 (Aut, Win, Spr) - Directed Reading in Biophysics
BIOPHYS 399 (Aut, Win, Spr, Sum) - Graduate Research
BIOPHYS 300 (Aut, Win, Spr, Sum) - Research and Special Advanced Work
CHEM 200 (Aut, Win, Spr) - Research in Chemistry
CHEM 301 (Aut, Win, Spr)
- Advanced Undergraduate Research
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Prior Year Courses
2023-24 Courses
- Chemistry in the Kitchen
CHEM 29N (Win)
2022-23 Courses
- Chemistry in the Kitchen
CHEM 29N (Win)
2021-22 Courses
- Chemistry in the Kitchen
CHEM 29N (Win)
- Chemistry in the Kitchen
Stanford Advisees
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Doctoral Dissertation Reader (AC)
Vishnu Shankar -
Postdoctoral Faculty Sponsor
Sandeep Bose, Yangjie Li, Yifan Meng -
Doctoral Dissertation Advisor (AC)
Joshua Lyu, Jinheng Xu
All Publications
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Unlocking the electrochemical functions of biomolecular condensates.
Nature chemical biology
2024
Abstract
Biomolecular condensation is a key mechanism for organizing cellular processes in a spatiotemporal manner. The phase-transition nature of this process defines a density transition of the whole solution system. However, the physicochemical features and the electrochemical functions brought about by condensate formation are largely unexplored. We here illustrate the fundamental principles of how the formation of condensates generates distinct electrochemical features in the dilute phase, the dense phase and the interfacial region. We discuss the principles by which these distinct chemical and electrochemical environments can modulate biomolecular functions through the effects brought about by water, ions and electric fields. We delineate the potential impacts on cellular behaviors due to the modulation of chemical and electrochemical environments through condensate formation. This Perspective is intended to serve as a general road map to conceptualize condensates as electrochemically active entities and to assess their functions from a physical chemistry aspect.
View details for DOI 10.1038/s41589-024-01717-y
View details for PubMedID 39327453
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Direct Conversion of N2 and Air to Nitric Acid in Gas-Water Microbubbles.
Journal of the American Chemical Society
2024
Abstract
We report a simple, direct, and green conversion of air/N2 to nitric acid by bubbling the gas through an aqueous solution containing 50 μM Fe2+ ions. Air stone, along with ultrasonication, was employed to generate gas microbubbles. H2O2 produced at the water-gas interface undergoes Fenton's reaction with Fe2+ ions to produce OH• that efficiently activates N2, yielding nitric acid as the final product. Nitrate (NO3-) formation occurs without the use of any external electric potential or radiation. The concentration of NO3- increased linearly with time over a period of 132 h. The average NO3- production rate is found to be 12.9 ± 0.05 μM h-1. We envision that this nitrogen fixation strategy that produces nitric acid in an eco-friendly way might open the possibility for the energy-efficient and green production of nitric acid.
View details for DOI 10.1021/jacs.4c11899
View details for PubMedID 39315452
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John I. Brauman (1937-2024).
Science (New York, N.Y.)
2024; 385 (6715): 1280
Abstract
Groundbreaking physical organic chemist.
View details for DOI 10.1126/science.ads7858
View details for PubMedID 39298608
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A developmental gradient reveals biosynthetic pathways to eukaryotic toxins in monocot geophytes.
Cell
2024
Abstract
Numerous eukaryotic toxins that accumulate in geophytic plants are valuable in the clinic, yet their biosynthetic pathways have remained elusive. A notable example is the >150 Amaryllidaceae alkaloids (AmAs), including galantamine, an FDA-approved treatment for Alzheimer's disease. We show that while AmAs accumulate to high levels in many daffodil tissues, biosynthesis is localized to nascent, growing tissue at the leaf base. A similar trend is found in the production of steroidal alkaloids (e.g., cyclopamine) in corn lily. This model of active biosynthesis enabled the elucidation of a complete set of biosynthetic genes that can be used to produce AmAs. Taken together, our work sheds light on the developmental and enzymatic logic of diverse alkaloid biosynthesis in daffodils. More broadly, it suggests a paradigm for biosynthesis regulation in monocot geophytes, where plants are protected from herbivory through active charging of newly formed cells with eukaryotic toxins that persist as above-ground tissue develops.
View details for DOI 10.1016/j.cell.2024.08.027
View details for PubMedID 39276773
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Fragment Correlation Mass Spectrometry Enables Direct Characterization of Disulfide Bond Cleavage Pathways of Therapeutic Peptides.
Analytical chemistry
2024
Abstract
Therapeutic peptides that are connected by disulfide bonds are often difficult to analyze by traditional tandem mass spectrometry without chemical modification. Using fragment correlation mass spectrometry, we analyzed 56 pairs of fragment ions generated from an equimolar (10 μM) mixture of three cyclic peptides, achieving sequence coverage of 86%, 100%, and 75% for octreotide, desmopressin, and the structural analogue of desmopressin, respectively. In all detected fragment ion pairs, only 20% of the fragment ions are terminal ions, with most of the measured ions only detected by fragment correlation mass spectrometry. From the peak volumes in the covariance map, we calculated branching ratios of each disulfide bond fragmentation pathway, providing a direct measurement of the probability of each fragmentation without requiring alteration of the chemical structure of the analytes.
View details for DOI 10.1021/acs.analchem.4c03202
View details for PubMedID 39248333
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Oxidation of Ammonia in Water Microdroplets Produces Nitrate and Molecular Hydrogen.
Environmental science & technology
2024
Abstract
Water microdroplets containing dissolved ammonia (30-300 μM) are sprayed through a copper oxide mesh with a 200 μm average pore size, resulting in the formation of nitrate (NO3-) and the release of molecular hydrogen (H2). The products result from a redox process that takes place at the liquid-solid interface through contact electrification, where no external potential is applied. Oxidation is initiated by superoxide radical anions (O2-) that originate from the oxygen in the air surrounding the microdroplets and from the hydroxyl radicals (OH•) originating from the water-air interface. Two spin traps (TEMPO and DMPO) capture these radicals as well as NH2OH+•, HNO, NO•, NO2•, and NOOH, which are detected by mass spectrometry. We also directly observed N2O2-• by the same means. We found that the hydrogen atom from the ammonia molecule can be set free not only in the form of H• but also as H2, which is detected using a residue gas analyzer. The oxidation process can be significantly enhanced by a factor of 3 when the sprayed microdroplets are irradiated with ultraviolet light (265 nm, 5 W). 35% of 300 μM ammonia can be degraded within 20 μs, and the nitrate conversion rate is estimated to be 15 nmol·mg-1·h-1.
View details for DOI 10.1021/acs.est.4c04568
View details for PubMedID 39178340
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Catalyst-Free Transformation of Carbon Dioxide to Small Organic Compounds in Water Microdroplets Nebulized by Different Gases.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
2024: e2406785
Abstract
A straightforward nebulized spray system is designed to explore the hydrogenation of carbon dioxide (CO2) within water microdroplets surrounded by different gases such as carbon dioxide, nitrogen, oxygen, and compressed air. The collected droplets are analyzed using water-suppressed nuclear magnetic resonance (NMR). Formate anion (HCOO-), acetate anion (CH3COO-), ethylene glycol (HOCH2CH2OH), and methane (CH4) are detected when water is nebulized. This pattern persisted when the water is saturated with CO2, indicating that CO2 in the nebulizing gas triggers the formation of these small organics. In a pure CO2 atmosphere, the formate anion concentration is determined to be ≈70 µm, referenced to dimethyl sulfoxide, which has been introduced as an internal standard in the collected water droplets. This study highlights the power of water microdroplets to initiate unexpected chemistry for the transformation of CO2 to small organic compounds.
View details for DOI 10.1002/advs.202406785
View details for PubMedID 39129358
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Fragment correlation mass spectrometry: Determining the structures of biopolymers in a complex mixture without isolating individual components.
Proceedings of the National Academy of Sciences of the United States of America
2024; 121 (32): e2409676121
Abstract
Fragment correlation mass spectrometry correlates ion pairs generated from the same fragmentation pathway, achieved by covariance mapping of tandem mass spectra generated with an unmodified linear ion trap without preseparation. We enable the identification of different precursors at different charge states in a complex mixture from a large isolation window, empowering an analytical approach for data-independent acquisition. The method resolves and matches isobaric fragments, internal ions, and disulfide bond fragments. We suggest that this method represents a major advance for analyzing structures of biopolymers in mixtures.
View details for DOI 10.1073/pnas.2409676121
View details for PubMedID 39074273
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Biomolecular condensates can function as inherent catalysts.
bioRxiv : the preprint server for biology
2024
Abstract
We report the discovery that chemical reactions such as ATP hydrolysis can be catalyzed by condensates formed by intrinsically disordered proteins (IDPs), which themselves lack any intrinsic ability to function as enzymes. This inherent catalytic feature of condensates derives from the electrochemical environments and the electric fields at interfaces that are direct consequences of phase separation. The condensates we studied were capable of catalyzing diverse hydrolysis reactions, including hydrolysis and radical-dependent breakdown of ATP whereby ATP fully decomposes to adenine and multiple carbohydrates. This distinguishes condensates from naturally occurring ATPases, which can only catalyze the dephosphorylation of ATP. Interphase and interfacial properties of condensates can be tuned via sequence design, thus enabling control over catalysis through sequence-dependent electrochemical features of condensates. Incorporation of hydrolase-like synthetic condensates into live cells enables activation of transcriptional circuits that depend on products of hydrolysis reactions. Inherent catalytic functions of condensates, which are emergent consequences of phase separation, are likely to affect metabolic regulation in cells.
View details for DOI 10.1101/2024.07.06.602359
View details for PubMedID 39026887
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Visualization of the Charging of Water Droplets Sprayed into Air.
The journal of physical chemistry. A
2024
Abstract
Water droplets are spraying into air using air as a nebulizing gas, and the droplets pass between two parallel metal plates with opposite charges. A high-speed camera records droplet trajectories in the uniform electric field, providing visual evidence for the Lenard effect, that is, smaller droplets are negatively charged whereas larger droplets are positively charged. By analyzing the velocities of the droplets between the metal plates, the charges on the droplets can be estimated. Some key observations include: (1) localized electric fields with intensities on the order of 109 V/m are generated, and charges are expected to jump (micro-lightening) between a positively charged larger droplet and the negatively charged smaller droplet as they separate; (2) the strength of the electric field is sufficiently powerful to ionize gases surrounding the droplets; and (3) observations in an open-air mass spectrometer reveal the presence of ions such as N2+, O2+, NO+, and NO2+. These findings provide new insight into the origins of some atmospheric ions and have implications for understanding ionization processes in the atmosphere and chemical transformations in water droplets, advancing knowledge in the field of aerosol science and water microdroplet chemistry.
View details for DOI 10.1021/acs.jpca.4c02981
View details for PubMedID 38968601
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Water Microdroplets Surrounded by Alcohol Vapor Cause Spontaneous Oxidation of Alcohols to Organic Peroxides.
Journal of the American Chemical Society
2024
Abstract
Using real-time mass spectrometric (MS) monitoring, we demonstrate one-step, catalyst-free spontaneous oxidation of various alcohols (ROH) to key reactive intermediates for the formation of ROO- compounds on the surface of water microdroplets surrounded by alcohol vapor, carried out under ambient conditions. These organic peroxides (POs) can act as important secondary organic aerosols (SOA). We used hydrogen-deuterium exchange by spraying D2O instead of H2O to learn about the reaction mechanism, and the results demonstrate the crucial role of the water-air interface in microdroplet chemistry. We find that the formation of POs relies on electron transfer occurring at the microdroplet interface, which generates hydrogen atoms and hydroxyl radicals that lead to a cascade of radical reactions. This electron transfer is believed to be driven by two factors: (1) the emergence of a strong electrostatic potential on the microdroplet's surface; and (2) the partial solvation of ions at the interface. Mass spectra reveal that the formation of POs is dependent on the alcohol structure, with tertiary alcohols showing a higher tendency to form organic peroxides than secondary alcohols, which in turn are more reactive than primary alcohols.
View details for DOI 10.1021/jacs.4c04092
View details for PubMedID 38935892
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Sprayed Oil-Water Microdroplets as a Hydrogen Source.
Journal of the American Chemical Society
2024
Abstract
Liquid water provides the largest hydrogen reservoir on the earth's surface. Direct utilization of water as a source of hydrogen atoms and molecules is fundamental to the evolution of the ecosystem and industry. However, liquid water is an unfavorable electron donor for forming these hydrogen species owing to its redox inertness. We report oil-mediated electron extraction from water microdroplets, which is easily achieved by ultrasonically spraying an oil-water emulsion. Based on charge measurement and electron paramagnetic resonance spectroscopy, contact electrification between oil and a water microdroplet is demonstrated to be the origin of electron extraction from water molecules. This contact electrification results in enhanced charge separation and subsequent mutual neutralization, which enables a ∼13-fold increase of charge carriers in comparison with an ultrapure water spray, leading to a ∼16-fold increase of spray-sourced hydrogen that can hydrogenate CO2 to selectively produce CO. These findings emphasize the potential of charge separation enabled by spraying an emulsion of liquid water and a hydrophobic liquid in driving hydrogenation reactions.
View details for DOI 10.1021/jacs.4c01455
View details for PubMedID 38573037
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Dependence on relative humidity in the formation of reactive oxygen species in water droplets.
Proceedings of the National Academy of Sciences of the United States of America
2024; 121 (12): e2315940121
Abstract
Water microdroplets (7 to 11 µm average diameter, depending on flow rate) are sprayed in a closed chamber at ambient temperature, whose relative humidity (RH) is controlled. The resulting concentration of ROS (reactive oxygen species) formed in the microdroplets, measured by the amount of hydrogen peroxide (H2O2), is determined by nuclear magnetic resonance (NMR) and by spectrofluorimetric assays after the droplets are collected. The results are found to agree closely with one another. In addition, hydrated hydroxyl radical cations (•OH-H3O+) are recorded from the droplets using mass spectrometry and superoxide radical anions (•O2-) and hydroxyl radicals (•OH) by electron paramagnetic resonance spectroscopy. As the RH varies from 15 to 95%, the concentration of H2O2 shows a marked rise by a factor of about 3.5 in going from 15 to 50%, then levels off. By replacing the H2O of the sprayed water with deuterium oxide (D2O) but keeping the gas surrounding droplets with H2O, mass spectrometric analysis of the hydrated hydroxyl radical cations demonstrates that the water in the air plays a dominant role in producing H2O2 and other ROS, which accounts for the variation with RH. As RH increases, the droplet evaporation rate decreases. These two facts help us understand why viruses in droplets both survive better at low RH values, as found in indoor air in the wintertime, and are disinfected more effectively at higher RH values, as found in indoor air in the summertime, thus explaining the recognized seasonality of airborne viral infections.
View details for DOI 10.1073/pnas.2315940121
View details for PubMedID 38489384
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Molecular Mechanism for Converting Carbon Dioxide Surrounding Water Microdroplets Containing 1,2,3-Triazole to Formic Acid.
Journal of the American Chemical Society
2024
Abstract
Spraying water microdroplets containing 1,2,3-triazole (Tz) has been found to effectively convert gas-phase carbon dioxide (CO2), but not predissolved CO2, into formic acid (FA). Herein, we elucidate the reaction mechanism at the molecular level through quantum chemistry calculations and ab initio molecular dynamics (AIMD) simulations. Computations suggest a multistep reaction mechanism that initiates from the adsorption of CO2 by Tz to form a CO2-Tz complex (named reactant complex (RC)). Then, the RC either is reduced by electrons that were generated at the air-liquid interface of the water microdroplet and then undergoes intramolecular proton transfer (PT) or switches the reduction and PT steps to form a [HCO2-(Tz-H)]- complex (named PC-). Subsequently, PC- undergoes reduction and the C-N bond dissociates to generate COOH- and [Tz-H]- (m/z = 69). COOH- easily converts to HCOOH and is captured at m/z = 45 in mass spectroscopy. Notably, the intramolecular PT step can be significantly lowered by the oriented electric field at the interface and a water-bridge mechanism. The mechanism is further confirmed by testing multiple azoles. The AIMD simulations reveal a novel proton transfer mechanism where water serves as a transporter and is shown to play an important role dynamically. Moreover, the transient COOH captured by the experiment is proposed to be partly formed by the reaction with H, pointing again to the importance of the air-water interface. This work provides valuable insight into the important mechanistic, kinetic, and dynamic features of converting gas-phase CO2 to valuable products by azoles or amines dissolved in water microdroplets.
View details for DOI 10.1021/jacs.4c00529
View details for PubMedID 38488449
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Evaluation of Oil-Absorbing Film for Imprint Desorption Electrospray Ionization Mass Spectrometry Imaging (IDESI-MSI) on Biological Samples.
Metabolites
2024; 14 (3)
Abstract
Imprint Desorption Electrospray Ionization Mass Spectrometry Imaging (IDESI-MSI) has proven to be a robust and reliable tool for chemically imaging biological samples such as fungi, animal tissues, and plants, but the choice of the imprint substrate is crucial. It must effectively transfer maximum amounts of species from the sample while preserving the original spatial distribution of detected molecules. In this study, we explored the potential of utilizing an oil-absorbing film, known for its soft nature and excellent lipophilicity, as an imprint substrate for IDESI-MSI on biological samples. To assess the transfer efficiency of the amounts of molecules and molecular patterns, we conducted experiments using mouse brain tissue. The result shows that more than 90% of the analytes can be transferred to the oil-absorbing film from the original tissue. A comparison of IDESI-MSI results between the oil-absorbing film and the original tissue demonstrates the material's capability to transfer most molecules from the original tissue and retain images of different analytes with high spatial fidelity. We extended our investigation to plant imaging, where we applied IDESI-MSI to a cross-section of okra. The oil-absorbing film exhibited promise in this context as well. These findings suggest that IDESI-MSI utilizing the oil-absorbing film holds potential across various research fields, including biological metabolism, chemistry, and clinical research, making this technique widely applicable.
View details for DOI 10.3390/metabo14030160
View details for PubMedID 38535320
View details for PubMedCentralID PMC10972117
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The power of microdroplet photochemistry.
Chemical science
2024; 15 (10): 3670-3672
Abstract
This study presents compelling evidence demonstrating that irradiation of the air-solution interface, whether achieved through the spraying of microdroplets into the air or by bubbling air through a solution, significantly accelerates the rate of photochemical reactions by orders of magnitude compared to identical reaction conditions in bulk solutions. We propose this approach as a novel and versatile method for harnessing solar energy in chemical transformations.
View details for DOI 10.1039/d4sc00056k
View details for PubMedID 38454998
View details for PubMedCentralID PMC10915808
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The power of microdroplet photochemistry
CHEMICAL SCIENCE
2024
View details for DOI 10.1039/d4sc00056k
View details for Web of Science ID 001156639100001
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Continuous ammonia synthesis from water and nitrogen via contact electrification.
Proceedings of the National Academy of Sciences of the United States of America
2024; 121 (4): e2318408121
Abstract
We synthesized ammonia (NH3) by bubbling nitrogen (N2) gas into bulk liquid water (200 mL) containing 50 mg polytetrafluoroethylene (PTFE) particles (~5 µm in diameter) suspended with the help of a surfactant (Tween 20, ~0.05 vol.%) at room temperature (25 °C). Electron spin resonance spectroscopy and density functional theory calculations reveal that water acts as the proton donor for the reduction of N2. Moreover, isotopic labeling of the N2 gas shows that it is the source of nitrogen in the ammonia. We propose a mechanism for ammonia generation based on the activation of N2 caused by electron transfer and reduction processes driven by contact electrification. We optimized the pH of the PTFE suspension at 6.5 to 7.0 and employed ultrasonic mixing. We found an ammonia production rate of ~420 μmol L-1 h-1 per gram of PTFE particles for the conditions described above. This rate did not change more than 10% over an 8-h period of sustained reaction.
View details for DOI 10.1073/pnas.2318408121
View details for PubMedID 38232282
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Noninvasive Detection of Skin Cancer by Imprint Desorption Electrospray Ionization Mass Spectrometry Imaging.
Analytical chemistry
2023
Abstract
We report a technique for the noninvasive detection of skin cancer by imprint desorption electrospray ionization mass spectrometry imaging (DESI-MSI) using a transfer agent that is pressed against the tissue of interest. By noninvasively pressing a tape strip against human skin, metabolites, fatty acids, and lipids on the skin surface are transferred to the tape with little spatial distortion. Running DESI-MSI on the tape strip provides chemical images of the molecules on the skin surface, which are valuable for distinguishing cancer from healthy skin. Chemical components of the tissue imprint on the tape strip and the original basal cell carcinoma (BCC) section from the mass spectra show high consistency. By comparing MS images (about 150-μm resolution) of same molecules from the tape strip and from the BCC section, we confirm that chemical patterns are successfully transferred to the tape stripe. We also used the technique to distinguish cherry angiomas from normal human skin by comparing the molecular patterns from a tape strip. These results demonstrate the potential of the imprint DESI-MSI technique for the noninvasive detection of skin cancers as well as other skin diseases before and during clinical surgery.
View details for DOI 10.1021/acs.analchem.3c04918
View details for PubMedID 38155587
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Superfast Formation of C(sp2)-N, C(sp2)-P, and C(sp2)-S Vinylic Bonds in Water Microdroplets.
Angewandte Chemie (International ed. in English)
2023: e202316131
Abstract
We report examples of C(sp2)-N, C(sp2)-S, and C(sp2)-P bond-forming transformations in water microdroplets at room temperature and atmospheric pressure using N2 as a nebulizing gas. When an aqueous solution of vinylic acid and amine is electrosprayed (+3 kV), the corresponding C(sp2)-N product is formed in a single step, which was characterized using mass spectrometry (MS) and tandem mass spectrometry (MS2). The scope of this reaction was extended to other amines and other unsaturated acids, including acrylic (CH2=CHCOOH) and crotonic (CH3CH=CHCOOH) acids. We also found that thiols and phosphines are viable nucleophiles, and the corresponding C(sp2)-S and C(sp2)-P products are observed in positive ion mode using MS and MS2.
View details for DOI 10.1002/anie.202316131
View details for PubMedID 38116872
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Water Microdroplets-Initiated Methane Oxidation.
Journal of the American Chemical Society
2023
Abstract
The special redox reactivity of water microdroplets causes "mild ignition" of methane gas to form methane oxygenates. The C(sp3)-H bond of methane can be activated by the hydroxyl radical (OH·) or the hydrogen radical (H·) across the air-water interface (AWI) of microdroplets to generate the methyl radical (CH3·). Once CH3· is formed, it undergoes free-radical reactions with O2 in the air, excessive OH· and H· across the AWI, and H2O2 present at the AWI and generated CH3· itself to produce methanol and other species. Production of the methanol and other oxygenates was confirmed by gas chromatography, mass spectrometry, and 1H- and 13C-nuclear magnetic resonance. Formic acid, acetic acid, ethanol, carbon dioxide, and methyl peroxide were also detected as methane oxidation byproducts. This water microdroplet-initiated oxidation process can be further enhanced under ultrasonication to yield 2.66 ± 0.77 mM methanol conversion from the methane gas in a single spray run for 30 min, with a selectivity of 19.2% compared with all other oxygenated species.
View details for DOI 10.1021/jacs.3c08643
View details for PubMedID 38054976
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Hydrocarbon Degradation by Contact with Anoxic Water Microdroplets.
Journal of the American Chemical Society
2023
Abstract
Oils are hydrophobic, but their degradation is frequently found to be accelerated in the presence of water microdroplets. The direct chemical consequences of water-oil contact have long been overlooked. We show that aqueous microdroplets in emulsified water-hexadecane (C16H34) mixtures can spontaneously produce CO2, •H, H2, and short-chain hydrocarbons (mainly C1 and C2) as detected by gas chromatography, electron paramagnetic resonance spectroscopy, and mass spectrometry. This reaction results from contact electrification at the water-oil microdroplet interface, in which reactive oxygen species are produced, such as hydrated hydroxyl radicals and hydrogen peroxide. We also find that the H2 originates from the water microdroplet and not the hydrocarbon it contacts. These observations highlight the potential of interfacial contact electrification to produce new chemistry.
View details for DOI 10.1021/jacs.3c07445
View details for PubMedID 37725034
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Valence Bond Theory Allows a Generalized Description of Hydrogen Bonding.
Journal of the American Chemical Society
2023
Abstract
This paper describes the nature of the hydrogen bond (HB), B:---H-A, using valence bond theory (VBT). Our analysis shows that the most important HB interactions are polarization and charge transfer, and their corresponding sum displays a pattern that is identical for a variety of energy decomposition analysis (EDA) methods. Furthermore, the sum terms obtained with the different EDA methods correlate linearly with the corresponding VB quantities. The VBT analysis demonstrates that the total covalent-ionic resonance energy (RECS) of the HB portion (B---H in B:---H-A) correlates linearly with the dissociation energy of the HB, ΔEdiss. In principle, therefore, RECS(HB) can be determined by experiment. The VBT wavefunction reveals that the contributions of ionic structures to the HB increase the positive charge on the hydrogen of the corresponding external/free O-H bonds in, for example, the water dimer compared with a free water molecule. This increases the electric field of the external O-H bonds of water clusters and contributes to bringing about catalysis of reactions by water droplets and in water-hydrophobic interfaces.
View details for DOI 10.1021/jacs.3c08196
View details for PubMedID 37664980
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One-Step, Catalyst-Free Formation of Phenol from Benzoic Acid Using Water Microdroplets.
Journal of the American Chemical Society
2023
Abstract
Benzoic acid dissolved in water is electrosprayed (-4 kV) by using nitrogen gas at a pressure of 120 psi to form ∼10 μm diameter microdroplets. Analysis with mass spectrometry (MS) and tandem mass spectrometry (MS2) of the resulting microdroplets shows the direct formation of phenol via decarboxylation without any catalyst or added reagents. This process represents an ecofriendly, environmentally benign method for producing phenol and related aromatic alcohols from their corresponding aromatic acids. The mechanism of this transformation was unambiguously characterized using mass spectrometry, radical trapping, and 18O labeling.
View details for DOI 10.1021/jacs.3c08638
View details for PubMedID 37624585
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Silica particles convert thiol-containing molecules to disulfides.
Proceedings of the National Academy of Sciences of the United States of America
2023; 120 (34): e2304735120
Abstract
Synthetic amorphous silica is a common food additive and a popular cosmetic ingredient. Mesoporous silica particles are also widely studied for their potential use in drug delivery and imaging applications because of their unique properties, such as tunable pore sizes, large surfaces areas, and assumed biocompatibility. Such a nanomaterial, when consisting of pure silicon dioxide, is generally considered to be chemically inert, but in this study, we showed that oxidation yields for different compounds were facilitated by simply incubating aqueous solutions with pure silica particles. Three thiol-containing molecules, L-cysteine, glutathione, and D-penicillamine, were studied separately, and it was found that more than 95% of oxidation happened after incubating any of these compounds with mesoporous silica particles in the dark for a day at room temperature. Oxidation increased over incubation time, and more oxidation was found for particles having larger surface areas. For nonporous silica particles at submicron ranges, yields of oxidation were different based on the structures of molecules, correlating with steric hindrance while accessing surfaces. We propose that the silyloxy radical (SiO•) on silica surfaces is what facilitates oxidation. Density functional theory calculations were conducted for total energy changes for reactions between different aqueous species and silicon dioxide surfaces. These calculations identified two most plausible pathways of the lowest energy to generate SiO• radicals from water radical cations H2O•+ and hydroxyl radicals •OH, previously known to exist at water interfaces.
View details for DOI 10.1073/pnas.2304735120
View details for PubMedID 37590411
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Contact between water vapor and silicate surface causes abiotic formation of reactive oxygen species in an anoxic atmosphere.
Proceedings of the National Academy of Sciences of the United States of America
2023; 120 (30): e2302014120
Abstract
Spontaneous generation of reactive oxygen species (ROS) in aqueous microdroplets or at a water vapor-silicate interface is a new source of redox chemistry. However, such generation occurs with difficulty in liquid water having a large ionic strength. We report that ROS is spontaneously produced when water vapor contacts hydrogen-bonded hydroxyl groups on a silicate surface. The evolution of hydrogen-bonded species such as hydroxyl groups was investigated by using two-dimensional, time-resolved FT-IR spectroscopy. The participation of water vapor in ROS generation is confirmed by investigating the reaction of D2O vapor and hydroxyl groups on a silicate surface. We propose a reaction pathway for ROS generation based on the change of the hydrogen-bonding network and corresponding electron transfer onto the silicate surface in the water vapor-solid contact process. Our observations suggest that ROS production from water vapor-silicate contact electrification could have contributed to oxidation during the Archean Eon before the Great Oxidation Event.
View details for DOI 10.1073/pnas.2302014120
View details for PubMedID 37459548
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Microlensed fiber allows subcellular imaging by laser-based mass spectrometry.
Nature protocols
2023
Abstract
Mass spectrometry imaging (MSI) enables the chemical mapping of molecules and elements in a label-free, high-throughput manner. Because this approach can be accomplished rapidly, it also enables chemical changes to be monitored. Here, we describe a protocol for MSI with subcellular spatial resolution. This is achieved by using a microlensed fiber, which is made by grinding an optical fiber. It is a universal and economic technique that can be adapted to most laser-based mass spectrometry methods. In this protocol, the output of laser radiation from the microlensed fiber causes laser ablation of the sample, and the resulting plume is mass spectrometrically analyzed. The microlensed fiber can be used with matrix-assisted laser desorption ionization, laser desorption ionization, laser ablation electrospray desorption ionization and laser ablation inductively coupled plasma, in each case to achieve submicroscale imaging of single cells and biological tissues. This report provides a detailed introduction of the microlensed fiber design and working principles, sample preparation, microlensed fiber ion source setup and multiple MSI platforms with different kinds of mass spectrometers. A researcher with a little background (such as a trained graduate student) is able to complete all the steps for the experimental setup in ~2 h, including fiber test, laser coupling and ion source modification. The imaging time spent mainly depends on the size of the imaging area. It is suggested that most existing laser-based MSI platforms, especially atmospheric pressure applications, can achieve breakthroughs in spatial resolution by introducing a microlensed fiber module.
View details for DOI 10.1038/s41596-023-00848-1
View details for PubMedID 37479826
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Interface of biomolecular condensates modulates redox reactions.
Chem
2023; 9 (6): 1594-1609
Abstract
Biomolecular condensates mediate diverse cellular processes. The density transition process of condensate formation results in selective partitioning of molecules, which define a distinct chemical environment within the condensates. However, the fundamental features of the chemical environment and the mechanisms by which such environment can contribute to condensate functions have not been revealed. Here, we report that an electric potential gradient, thereby an electric field, is established at the liquid-liquid interface between the condensate and the bulk environment due to the density transition of ions and molecules brought about by phase separation. We find that the interface of condensates can drive spontaneous redox reactions in vitro and in living cells. Our results uncover a fundamental physicochemical property of the interface of condensates and the mechanism by which the interface can modulate biochemical activities.
View details for DOI 10.1016/j.chempr.2023.04.001
View details for PubMedID 37546704
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Distinguishing Renal Cell Carcinoma From Normal Kidney Tissue Using Mass Spectrometry Imaging Combined With Machine Learning.
JCO precision oncology
2023; 7: e2200668
Abstract
Accurately distinguishing renal cell carcinoma (RCC) from normal kidney tissue is critical for identifying positive surgical margins (PSMs) during partial and radical nephrectomy, which remains the primary intervention for localized RCC. Techniques that detect PSM with higher accuracy and faster turnaround time than intraoperative frozen section (IFS) analysis can help decrease reoperation rates, relieve patient anxiety and costs, and potentially improve patient outcomes.Here, we extended our combined desorption electrospray ionization mass spectrometry imaging (DESI-MSI) and machine learning methodology to identify metabolite and lipid species from tissue surfaces that can distinguish normal tissues from clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC) tissues.From 24 normal and 40 renal cancer (23 ccRCC, 13 pRCC, and 4 chRCC) tissues, we developed a multinomial lasso classifier that selects 281 total analytes from over 27,000 detected molecular species that distinguishes all histological subtypes of RCC from normal kidney tissues with 84.5% accuracy. On the basis of independent test data reflecting distinct patient populations, the classifier achieves 85.4% and 91.2% accuracy on a Stanford test set (20 normal and 28 RCC) and a Baylor-UT Austin test set (16 normal and 41 RCC), respectively. The majority of the model's selected features show consistent trends across data sets affirming its stable performance, where the suppression of arachidonic acid metabolism is identified as a shared molecular feature of ccRCC and pRCC.Together, these results indicate that signatures derived from DESI-MSI combined with machine learning may be used to rapidly determine surgical margin status with accuracies that meet or exceed those reported for IFS.
View details for DOI 10.1200/PO.22.00668
View details for PubMedID 37285559
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A developmental gradient reveals biosynthetic pathways to eukaryotic toxins in monocot geophytes.
bioRxiv : the preprint server for biology
2023
Abstract
Numerous eukaryotic toxins that accumulate in geophytic plants are valuable in the clinic, yet their biosynthetic pathways have remained elusive. A lead example is the >150 Amaryllidaceae alkaloids (AmAs) including galantamine, an FDA-approved treatment for Alzheimer's disease. We show that while AmAs accumulate to high levels in many tissues in daffodils, biosynthesis is localized to nascent, growing tissue at the base of leaves. A similar trend is found for the production of steroidal alkaloids (e.g. cyclopamine) in corn lily. This model of active biosynthesis enabled elucidation of a complete set of biosynthetic genes for the production of AmAs. Taken together, our work sheds light on the developmental and enzymatic logic of diverse alkaloid biosynthesis in daffodil. More broadly, it suggests a paradigm for biosynthesis regulation in monocot geophytes where plants are protected from herbivory through active charging of newly formed cells with eukaryotic toxins that persist as aboveground tissue develops.
View details for DOI 10.1101/2023.05.12.540595
View details for PubMedID 37214939
View details for PubMedCentralID PMC10197729
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Chemical imaging reveals diverse functions of tricarboxylic acid metabolites in root growth and development.
Nature communications
2023; 14 (1): 2567
Abstract
Understanding how plants grow is critical for agriculture and fundamental for illuminating principles of multicellular development. Here, we apply desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to the chemical mapping of the developing maize root. This technique reveals a range of small molecule distribution patterns across the gradient of stem cell differentiation in the root. To understand the developmental logic of these patterns, we examine tricarboxylic acid (TCA) cycle metabolites. In both Arabidopsis and maize, we find evidence that elements of the TCA cycle are enriched in developmentally opposing regions. We find that these metabolites, particularly succinate, aconitate, citrate, and α-ketoglutarate, control root development in diverse and distinct ways. Critically, the developmental effects of certain TCA metabolites on stem cell behavior do not correlate with changes in ATP production. These results present insights into development and suggest practical means for controlling plant growth.
View details for DOI 10.1038/s41467-023-38150-z
View details for PubMedID 37142569
View details for PubMedCentralID 3612672
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Making ammonia from nitrogen and water microdroplets.
Proceedings of the National Academy of Sciences of the United States of America
2023; 120 (16): e2301206120
Abstract
Water (H2O) microdroplets are sprayed onto a magnetic iron oxide (Fe3O4) and Nafion-coated graphite mesh using compressed N2 or air as the nebulizing gas. The resulting splash of microdroplets enters a mass spectrometer and is found to contain ammonia (NH3). This gas-liquid-solid heterogeneous catalytic system synthesizes ammonia in 0.2 ms. The conversion rate reaches 32.9 ± 1.38 nmol s-1 cm-2 at room temperature without application of an external electric potential and without irradiation. Water microdroplets are the hydrogen source for N2 in contact with Fe3O4. Hydrazine (H2NNH2) is also observed as a by-product and is suspected to be an intermediate in the formation of ammonia. This one-step nitrogen-fixation strategy to produce ammonia is eco-friendly and low cost, which converts widely available starting materials into a value-added product.
View details for DOI 10.1073/pnas.2301206120
View details for PubMedID 37036968
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One-Step Formation of Pharmaceuticals Having a Phenylacetic Acid Core Using Water Microdroplets.
Journal of the American Chemical Society
2023
Abstract
The properties of water microdroplets strikingly differ from bulk water. Using room-temperature water microdroplets, we find that toluene can react with CO2 to form phenylacetic acid in one step without any catalyst with negative high voltage applied at the sprayer source. The chemical components of these microdroplets are identified by mass spectrometry, and product structures are confirmed by tandem mass spectrometry. In this manner, we generate three drug molecules in a single step: 4-aminophenylacetic acid (epithelial peptide transporter PepT1 inhibitor), 3,4-dihydroxyphenylacetic acid (dopamine metabolite neurotransmitter), and phenylacetic acid (sodium salt form; treatment of urea cycle disorder). Mechanistic studies show that benzyl radicals formed from hydroxyl radicals at the water microdroplet interface drive these carboxylation reactions. This water microdroplet chemistry is general, allowing activation and subsequent carboxylation of aryl α-C-H groups.
View details for DOI 10.1021/jacs.3c00773
View details for PubMedID 37011129
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All-perfluoropolymer, nonlinear stability-assisted monolithic surface combines topology-specific superwettability with ultradurability.
Innovation (Cambridge (Mass.))
2023; 4 (2): 100389
Abstract
Developing versatile and robust surfaces that mimic the skins of living beings to regulate air/liquid/solid matter is critical for many bioinspired applications. Despite notable achievements, such as in the case of developing robust superhydrophobic surfaces, it remains elusive to realize simultaneously topology-specific superwettability and multipronged durability owing to their inherent tradeoff and the lack of a scalable fabrication method. Here, we present a largely unexplored strategy of preparing an all-perfluoropolymer (Teflon), nonlinear stability-assisted monolithic surface for efficient regulating matters. The key to achieving topology-specific superwettability and multilevel durability is the geometric-material mechanics design coupling superwettability stability and mechanical strength. The versatility of the surface is evidenced by its manufacturing feasibility, multiple-use modes (coating, membrane, and adhesive tape), long-term air trapping in 9-m-deep water, low-fouling droplet transportation, and self-cleaning of nanodirt. We also demonstrate its multilevel durability, including strong substrate adhesion, mechanical robustness, and chemical stability, all of which are needed for real-world applications.
View details for DOI 10.1016/j.xinn.2023.100389
View details for PubMedID 36895759
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Indoor pollution: avoid harmful control measures.
Nature
2023; 615 (7952): 394
View details for DOI 10.1038/d41586-023-00769-9
View details for PubMedID 36918674
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Mechanism-Guided Design of Robust Palladium Catalysts for Selective Aerobic Oxidation of Polyols.
Journal of the American Chemical Society
2023
Abstract
The palladium complex [(L1)Pd(mu-OAc)]2[OTf]2 (L1 = neocuproine) is a selective catalyst for the aerobic oxidation of vicinal polyols to alpha-hydroxyketones, but competitive oxidation of the ligand methyl groups limits the turnover number and necessitates high Pd loadings. Replacement of the neocuproine ligand with 2,2'-biquinoline ligands was investigated as a strategy to improve catalyst performance and explore the relationship between ligand structure and reactivity. Evaluation of [(L2)Pd(mu-OAc)]2[OTf]2 (L2 = 2,2'-biquinoline) as a catalyst for aerobic alcohol oxidation revealed a threefold enhancement in turnover number relative to the neocuproine congener, but a much slower rate. Mechanistic studies indicated that the slow rates observed with L2 were a consequence of precipitation of an insoluble trinuclear palladium species─(L2Pd)3(mu-O)22+─formed during catalysis and characterized by high-resolution electrospray ionization mass spectrometry. Density functional theory was used to predict that a sterically modified biquinoline ligand, L3 = 7,7'-di-tert-butyl-2,2'-biquinoline, would disfavor the formation of the trinuclear (LPd)3(mu-O)22+ species. This design strategy was validated as catalytic aerobic oxidation with [(L3)Pd(mu-OAc)]2[OTf]2 is both robust and rapid, marrying the kinetics of the parent L1-supported system with the high aerobic turnover numbers of the L2-supported system. Changes in ligand structure were also found to modulate regioselectivity in the oxidation of complex glycoside substrates, providing new insights into structure-selectivity relationships with this class of catalysts.
View details for DOI 10.1021/jacs.2c10667
View details for PubMedID 36657018
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Rapid Characterization of Antibodies via Automated Flow Injection Coupled with Online Microdroplet Reactions and Native-pH Mass Spectrometry.
Analytical chemistry
2023
Abstract
Microdroplet reactions have aroused much interest due to significant reaction acceleration (e.g., ultrafast protein digestion in microdroplets could occur in less than 1 ms). This study integrated a microdroplet protein digestion technique with automated sample flow injection and online mass spectrometry (MS) analysis, to develop a rapid and robust method for structural characterization of monoclonal antibodies (mAbs) that is essential to assess the antibody drug's safety and quality. Automated sequential aspiration and mixing of an antibody and an enzyme (IdeS or IgdE) enabled rapid analysis with high reproducibility (total analysis time: 2 min per sample; reproducibility: 2% coefficient of variation). Spraying the sample in ammonium acetate buffer (pH 7) using a jet stream source allowed efficient digestion of antibodies and efficient ionization of resulting antibody subunits under native-pH conditions. Importantly, it also provided a platform to directly study specific binding of an antibody and an antigen (e.g., detecting the complexes mAb/RSFV antigen and F(ab')2/RSVF in this study). Furthermore, subsequent tandem MS analysis of a resulting subunit from microdroplet digestion enabled localizing post-translational modifications on particular domains of a mAb in a rapid fashion. In combination with IdeS digestion of an antibody, additional tris(2-carboxyethyl)phosphine (TCEP) reduction and N-glycosidase F (PNGase F) deglycosylation reactions that facilitate antibody analysis could be realized in "one-pot" spraying. Interestingly, increased deglycosylation yield in microdroplets was found, simply by raising the sample temperature. We expect that our method would have a high impact for rapid characterization of monoclonal antibodies.
View details for DOI 10.1021/acs.analchem.2c04535
View details for PubMedID 36656670
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Silicone Wristband Spray Ionization Mass Spectrometry for Combined Exposome and Metabolome Profiling
ISRAEL JOURNAL OF CHEMISTRY
2023
View details for DOI 10.1002/ijch.202200116
View details for Web of Science ID 000912502200001
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Immuno-Desorption Electrospray Ionization Mass Spectrometry Imaging Identifies Functional Macromolecules by Using Microdroplet-Cleavable Mass Tags.
Angewandte Chemie (International ed. in English)
2023
Abstract
We present immunoassay-based desorption electrospray ionization mass spectrometry imaging (immuno-DESI-MSI) to visualize functional macromolecules such as drug targets and cascade signaling factors. A set of boronic acid mass tags (BMTs) were synthesized to label antibodies as MSI probes. The boronic ester bond is employed to cross-link the BMT with the galactosamine-modified antibody. The BMT can be released from its tethered antibody by ultrafast cleavage of the boronic ester bond caused by the acidic condition of sprayed DESI microdroplets containing water. The fluorescent moiety enables the BMT to work in both optical and MS imaging modes. The positively charged quaternary ammonium group enhances the ionization efficiency. The introduction of the boron element also makes mass tags readily identified because of its unique isotope pattern. Immuno-DESI-MSI provides an appealing strategy to spatially map macromolecules beyond what can be observed by conventional DESI-MSI, provided antibodies are available to the targetted molecules of interest.
View details for DOI 10.1002/anie.202216969
View details for PubMedID 36622964
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Catalyst-Free Decarboxylative Amination of Carboxylic Acids in Water Microdroplets.
Journal of the American Chemical Society
2022
Abstract
Previous studies have shown that hydroxyl radicals can be formed at the water-gas surface of water microdroplets. We report the use of in situ generated hydroxyl radicals to carry out an organic transformation in one step, namely, the formation of anilines from aryl acids as well as both ammonia and primary/secondary amines via decarboxylation. Benzoic acids and amines are dissolved in water, and the solution is sprayed to form microdroplets whose chemical contents are analyzed mass spectrometrically. All intermediates and products are determined using mass spectrometry (MS) as well as in some cases tandem mass spectrometry (MS2). These results support the following reaction mechanism: NR2OH, formed via reaction of the amine with •OH, reacts with benzoic acid to form an isocyanate via a Lossen rearrangement. Hydrolysis followed by liberation of CO2 then delivers the aniline product. Notably, the scope of this transformation includes a variety of amines and aromatic acids and enables their conversion into aniline and N-substituted anilines, all in a single step. Additionally, this reaction occurs at room temperature and does not require metal catalysts or organic solvents.
View details for DOI 10.1021/jacs.2c12236
View details for PubMedID 36566437
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Quantum Controlled Cold Scattering Challenges Theory.
The journal of physical chemistry letters
2022: 10912-10917
Abstract
Our previous rotationally inelastic cold scattering experiments between state prepared D2 (v = 2, j = 2, m = 0) and He disagreed with theory, raising serious concerns about either our understanding of the anisotropic potential or the accuracy of the measurement. To further interrogate interactions between molecular hydrogen and atomic helium, we study the Deltaj = 1and Deltaj = 2 rotational relaxation of HD (v = 2, j = 2, m = 0) by collision with He. The two rotational transitions probe different anisotropic components of the van der Waals potential. Our state resolved scattering study shows that these two transitions are mediated by two different shape resonances l = 1 for Deltaj = 1 and l = 2 for Deltaj = 2. The strong l = 1 resonance dominates the Deltaj = 1 scattering, agreeing with theory. However, the dominance of the weaker l = 2 resonance in the Deltaj = 2 transition, which matches our earlier D2-He result, contradicts theoretical calculations. The continued contradiction, when we expect one-to-one correspondence between our stereodynamically controlled scattering experiment and theoretical calculations, makes us question the accuracy of the weaker anisotropic part of the H2-He interaction potential.
View details for DOI 10.1021/acs.jpclett.2c03038
View details for PubMedID 36394562
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Direct C(sp3)-N Bond Formation between Toluene and Amine in Water Microdroplets.
Journal of the American Chemical Society
2022
Abstract
Unlike the inertness of bulk water, water microdroplets exhibit some remarkable reactivities. We report that water microdroplets can directly produce stable C7H7+ cations (a combination of benzylic and tropylium cations) from toluene and other substrates at room temperature with a positive voltage (+4 kV) applied to the droplet spray source. The C7H7+ cation and the benzyl radical (C6H5CH2·) are both generated via hydroxyl radicals at the water-gas interface of the microdroplets. The C7H7+ signal is observed directly by mass spectrometry. Dissolved amines (primary, secondary, and tertiary) in the microdroplets can react with both C7H7+ and C6H5CH2· to form the corresponding alkyl C(sp3)-N coupling products in one step, which cannot be achieved in bulk water or other solvents. The products were identified using tandem mass spectrometry (MS2) and 1H NMR spectroscopy. Notably, the direct C(sp3)-N bond formation products were obtained in the absence of a catalyst. In the presence of a radical scavenger, the mass spectra of the C(sp3)-N coupling products are strongly suppressed, which supports the hypothesis that this reaction is driven by hydroxyl radicals generated in the water microdroplets. Taken together, these results show that water microdroplets provide a new method for direct one-step C(sp3)-N bond formation without the need for a metal catalyst.
View details for DOI 10.1021/jacs.2c10032
View details for PubMedID 36255242
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Resonant cold scattering of highly vibrationally excited D2 with Ne.
The Journal of chemical physics
2022; 157 (14): 144301
Abstract
To accurately map weak D2-Ne long-range interactions, we have studied rotationally inelastic cold scattering of D2 prepared in the vibrationally excited (v = 4) and rotationally aligned (j = 2, m) quantum state within the moving frame of a supersonically expanded mixed molecular beam. In contrast to earlier high energy D2-Ne collision experiments, the (j = 2 → j' = 0) cold scattering produced highly symmetric angular distributions that strongly suggest a resonant quasi-bound collision complex that lives long enough to make a few rotations. Our partial wave analysis indicates that the scattering dynamics is dominated by a single resonant l = 2 orbital, even in the presence of a broad temperature (0-5 K) distribution that allows incoming orbitals up to l = 5. The dominance of a single orbital suggests that the resonant complex stabilizes through the coupling of the internal (j = 2) and orbital (l = 2) angular momentum to produce a total angular momentum of J = 0 for the D2-Ne complex.
View details for DOI 10.1063/5.0114349
View details for PubMedID 36243531
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Simple Estimate of the Potential Drop across an Amphiprotic Liquid-Liquid Interface.
The journal of physical chemistry. B
2022
Abstract
Two immiscible liquids in contact with each other can have different internal electrostatic potentials. An associated electric double layer (EDL) therefore exists within each liquid. For amphiprotic liquids, the exchange of protons between the two liquids gives rise to two EDLs, a positively charged EDL in one of the liquids and negatively charged EDL in the other. Using the pKa and pKb of one liquid dissolved in the other and the pH equivalent within each amphiprotic liquid, we can estimate the potential drop, Deltaphi, between the interior of the two liquids, also known as the Galvani potential or liquid-liquid junction potential. This estimation is independent of surface charge and ionic strength. By using the ionic strength to find the thickness of the EDL, we also estimate the average electric field strength across the interface. For the special case of water (H2O) in contact with an immiscible alcohol (ROH), the potential drop across the interface from the water to the alcohol is Deltaphi = 2.303VT (pKb + pH - pKw - pH2OR), where VT is the thermal voltage at a given temperature T.
View details for DOI 10.1021/acs.jpcb.2c05696
View details for PubMedID 36194396
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Reply to Brzeski and Jordan: Potential pyridine tautomers that can form stable dipole-bound anions.
Proceedings of the National Academy of Sciences of the United States of America
2022; 119 (38): e2212433119
View details for DOI 10.1073/pnas.2212433119
View details for PubMedID 36095181
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Spraying Water Microdroplets Containing 1,2,3-Triazole Converts Carbon Dioxide into Formic Acid.
Journal of the American Chemical Society
2022
Abstract
We report the use of 1,2,3-triazole (Tz)-containing water microdroplets for gas-phase carbon dioxide (CO2) reduction at room temperature. Using a coaxial sonic spraying setup, the CO2 can be efficiently captured by Tz and converted to formic acid (HCOOH; FA) at the gas-liquid interface (GLI). A mass spectrometer operated in negative ion mode monitors the capture of CO2 to form the bicarbonate anion (HCO3-) and conversion to form the formate anion (HCOO-). Varied FA species were successfully identified by MS/MS experiments including the formate monomer ([FA - H]-, m/z 45), the dimer ([2FA - H]-, m/z 91; [2FA + Na - 2H]-, m/z 113), the trimer ([3FA - H]-, m/z 137), and some other adducts (such as [FA - H + H2CO3]-, m/z 107; [2FA + Na - 2H + Tz]-, m/z 182). The reaction conditions were systematically optimized to make the maximum conversion yield reach over 80% with an FA concentration of approximately 71 ± 3.1 μM. The mechanism for the reaction is speculated to be that Tz donates the proton and the hydroxide (OH-) at the GLI, resulting in a stepwise yield of electrons to reduce gas-phase CO2 to FA.
View details for DOI 10.1021/jacs.2c07779
View details for PubMedID 36075012
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On-demand electrochemically controlled compound release from an ultrasonically powered implant.
RSC advances
2022; 12 (36): 23337-23345
Abstract
On-demand drug delivery systems are promising for a wide range of therapeutic applications. When combined with wireless implants for controlled drug delivery, they can reduce overall dosage and side effects. Here, we demonstrate release of fluorescein from a novel on-demand release system for negatively charged compounds. The release system is based on a modified electroresponsive polypyrrole nanoparticulate film designed to minimize ion exchange with the stored compound - a major passive leakage mechanism. We further designed an ultrasonically powered mm-sized implant to electronically control the on-demand drug delivery system in vivo. Release kinetics are characterized both in vitro and in vivo in mice using fluorescein as a model drug, demonstrating the feasibility of wireless, controllable drug release using an ultrasonically powered implant.
View details for DOI 10.1039/d2ra03422k
View details for PubMedID 36090393
View details for PubMedCentralID PMC9382542
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On-demand electrochemically controlled compound release from an ultrasonically powered implant
RSC ADVANCES
2022; 12 (36): 23337-23345
View details for DOI 10.1039/d2ra03422k
View details for Web of Science ID 000841167500001
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Water-solid contact electrification causes hydrogen peroxide production from hydroxyl radical recombination in sprayed microdroplets.
Proceedings of the National Academy of Sciences of the United States of America
2022; 119 (32): e2209056119
Abstract
Contact electrification between water and a solid surface is crucial for physicochemical processes at water-solid interfaces. However, the nature of the involved processes remains poorly understood, especially in the initial stage of the interface formation. Here we report that H2O2 is spontaneously produced from the hydroxyl groups on the solid surface when contact occurred. The density of hydroxyl groups affects the H2O2 yield. The participation of hydroxyl groups in H2O2 generation is confirmed by mass spectrometric detection of 18O in the product of the reaction between 4-carboxyphenylboronic acid and 18O-labeled H2O2 resulting from 18O2 plasma treatment of the surface. We propose a model for H2O2 generation based on recombination of the hydroxyl radicals produced from the surface hydroxyl groups in the water-solid contact process. Our observations show that the spontaneous generation of H2O2 is universal on the surfaces of soil and atmospheric fine particles in a humid environment.
View details for DOI 10.1073/pnas.2209056119
View details for PubMedID 35914139
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Enzyme-photo-coupled catalysis in gas-sprayed microdroplets.
Chemical science
2022; 13 (28): 8341-8348
Abstract
Enzyme-photo-coupled catalysis produces fine chemicals by combining the high selectivity of an enzyme with the green energy input of sunlight. Operating a large-scale system, however, remains challenging because of the significant loss of enzyme activity caused by continuous illumination and the difficulty in utilizing solar energy with high efficiency at large scale. We present a large-scale enzyme-photo-coupled catalysis system based on gas-sprayed microdroplets. By this means, we demonstrate a 43.6-71.5 times improvement of solar energy utilization over that using a traditional bulk processing system. Owing to the improved enzyme activity in microdroplets, we show that chiral alcohols can be produced with up to a 2.2-fold increase in the reaction rate and a 5.6-fold increase in final product concentration.
View details for DOI 10.1039/d2sc02791g
View details for PubMedID 35919726
View details for PubMedCentralID PMC9297532
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Laser Ablation Electrospray Ionization Achieves 5 mum Resolution Using a Microlensed Fiber.
Analytical chemistry
2022
Abstract
A pulsed (10 Hz) infrared (IR) (1064 nm) laser is focused on a sample surface by means of a microlensed fiber. Analytes desorbed from the surface are captured by charged microdroplets before entering a mass spectrometer. By translating the sample surface, a chemical map is generated with a resolution of 5 mum, defined as the change from 20 to 80% of the analyte signal intensity. As a demonstration of the power of this new imaging technique, analytes from a parsnip root section are imaged and compared with that obtained from conventional laser ablation electrospray ionization mass spectrometry. The improvement in spatial resolution is about a factor of 20.
View details for DOI 10.1021/acs.analchem.2c01942
View details for PubMedID 35797218
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Enzyme-photo-coupled catalysis in gas-sprayed microdroplets
CHEMICAL SCIENCE
2022
View details for DOI 10.1039/d2sc02791g
View details for Web of Science ID 000818030500001
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Capture of Hydroxyl Radicals by Hydronium Cations in Water Microdroplets.
Angewandte Chemie (International ed. in English)
2022
Abstract
Despite the high stability of bulk water, water microdroplets possess strikingly different properties, such as the presence of hydroxyl radicals (OH) at the air-water interface. Previous studies exhibited the recombination of OH into H 2 O 2 molecules and the capture of OH by oxidizing other molecules. By spraying pure water microdroplets into a mass spectrometer, we detected OH in the form of (H 4 O 2 ) + that is essentially OH--H 3 O + , a hydroxyl radical combined with a hydronium cation through hydrogen bonding. We also successfully captured it with two OH scavengers, caffeine and melatonin, and key oxidation radical intermediates that bear important mechanistic information were seen. It is suggested that some previous reactions involving (H 4 O 2 ) + should be attributed to reactions with OH--H 3 O + rather than with the water dimer cation (H 2 O-OH 2 ) + .
View details for DOI 10.1002/anie.202207587
View details for PubMedID 35700155
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Investigation of Tryptic Protein Digestion in Microdroplets and in Bulk Solution.
Journal of the American Society for Mass Spectrometry
2022
Abstract
Recent studies have shown that ultrafast enzymatic digestion of proteins can be achieved in microdroplet within 250 mus. Further investigation of peptides resulting from microdroplet digestion (MD) would be necessary to evaluate it as an alternative to the conventional bulk digestion for bottom-up and biotherapeutic protein characterization. Herein we examined and compared protein tryptic digestion in both MD and bulk solution. In the case of MD of beta-lactoglobulin B, the preservation of long peptides was observed due to the short digestion time. In addition, MD is applicable to digest both high- and low-abundance proteins in mixture. In the case of digesting NIST 8671 mAb antibody containing a low level of commonly encountered host cell protein (HCP) PLBL2 (mAb:PLBL2 = 100:1 by weight), MD produced lower levels of digestion-induced chemical modifications of asparagine/glutamine deamidation, compared with overnight digestion. No significant difference between MD and bulk digestion was observed in terms of trypsin digestion specificity based on examination of semi- and unspecific-cleaved peptides. Our study suggests that MD, a fast digestion approach, could be adopted for bottom-up proteomics research and for peptide mapping of mAbs to characterize site-specific deamidation and glycosylation, for the purpose of development of biopharmaceuticals.
View details for DOI 10.1021/jasms.2c00072
View details for PubMedID 35647885
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Insights into electrochemiluminescence dynamics by synchronizing real-time electrical, luminescence, and mass spectrometric measurements.
Chemical science
2022; 13 (21): 6244-6253
Abstract
Electrochemiluminescence (ECL) comprises a sophisticated cascade of reactions. Despite advances in mechanistic studies by electrochemistry and spectroscopy, a lack of access to dynamic molecular information renders many plausible ECL pathways unclear or unproven. Here we describe the construction of a real-time ECL mass spectrometry (MS) platform (RT-Triplex) for synchronization of dynamic electrical, luminescent, and mass spectrometric outputs during ECL events. This platform allows immediate and continuous sampling of newly born species at the Pt wire electrode of a capillary electrochemical (EC) microreactor into MS, enabling characterization of short-lived intermediates and the multi-step EC processes. Two ECL pathways of luminol are validated by observing the key intermediates α-hydroxy hydroperoxide and diazaquinone and unraveling their correlation with applied voltage and ECL emission. Moreover, a "catalytic ECL route" of boron dipyrromethene (BODIPY) involving homogeneous oxidation of tri-n-propylamine with the BODIPY radical cation is proposed and verified.
View details for DOI 10.1039/d2sc01317g
View details for PubMedID 35733885
View details for PubMedCentralID PMC9159085
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Coherent Preparation of Highly Vibrating and Rotating D2 Molecules.
The journal of physical chemistry letters
2022: 4682-4687
Abstract
Highly vibrationally and rotationally excited hydrogen molecules are of immense interest for understanding and modeling the physics and chemistry of the cold interstellar medium. Using a sequence of two Stark-induced adiabatic Raman passages, we demonstrate the preparation of rotationally excited D2 molecules in the fourth excited vibrational level within its ground electronic state. The nearly complete population transfer to the target state is confirmed by observing both the threshold behavior as a function of the laser power and the depletion of the intermediate level. The vibrational excitation reported here opens new possibilities in the study of the much debated four-center reaction between a pair of hydrogen molecules. Additionally, these rovibrationally excited molecules could be potentially used to generate the high-intensity D- ion beams considered essential for D-T thermonuclear fusion by enhancing the cross section for dissociative electron attachment by 5 orders of magnitude compared to that of the ground state.
View details for DOI 10.1021/acs.jpclett.2c01209
View details for PubMedID 35605182
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Coherent Preparation of Highly Vibrating and Rotating D-2 Molecules
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
2022
View details for DOI 10.1021/acsjpclett.2c01209
View details for Web of Science ID 000819525900001
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Insights into electrochemiluminescence dynamics by synchronizing real-time electrical, luminescence, and mass spectrometric measurements
CHEMICAL SCIENCE
2022
View details for DOI 10.1039/d2sc01317g
View details for Web of Science ID 000793901100001
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Anisotropic dynamics of resonant scattering between a pair of cold aligned diatoms.
Nature chemistry
2022
Abstract
The collision dynamics between a pair of aligned molecules in the presence of a partial-wave resonance provide the most sensitive probe of the long-range anisotropic forces important to chemical reactions. Here we control the collision temperature and geometry to probe the dynamics of cold (1-3K) rotationally inelastic scattering of a pair of optically state-prepared D2 molecules. The collision temperature is manipulated by combining the gating action of laser state preparation and detection with the velocity dispersion of the molecular beam. When the bond axes of both molecules are aligned parallel to the collision velocity, the scattering rate drops by a factor of 3.5 as collision energies >2.1K are removed, suggesting a geometry-dependent resonance. Partial-wave analysis of the measured angular distribution supports a shape resonance within the centrifugal barrier of the l=2 incoming orbital. Our experiment illustrates the strong anisotropy of the quadrupole-quadrupole interaction that controls the dynamics of resonant scattering.
View details for DOI 10.1038/s41557-022-00926-z
View details for PubMedID 35501483
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Capturing Reactive Carbanions by Microdroplets.
Journal of the American Chemical Society
2022
Abstract
Carbanions appear in many organic or biological reactions as fleeting intermediates, prohibiting direct observation or spectroscopic measurement. An aqueous environment is known to rapidly annihilate a carbanion species, reducing its lifetime to as short as picoseconds. We report that aqueous microdroplets can capture and stabilize reactive carbanion intermediates isolated from four classic organic reactions, aldol and Knoevenagel condensations, alkyne alkylation, and the Reimer-Tiemann reaction, enabling the detection of their carbanion intermediates by desorption electrospray ionization mass spectrometry. This is accomplished in real time of the reaction, allowing new insights into reaction mechanisms to be obtained. The efficacy of microdroplets in capturing such elusive species was examined by varying the solvent and the microdroplet negative charge density. We observed that microdroplets composed of water-methanol outperform other solvents, such as pure water, in capturing carbanions, which is in contrast to the earlier report that presented the highest performance of pure water microdroplets in capturing carbocations. We offer some mechanistic insights to explain the discriminatory behavior of these two oppositely charged species in microdroplets.
View details for DOI 10.1021/jacs.2c01577
View details for PubMedID 35452233
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Sprayed Water Microdroplets Are Able to Generate Hydrogen Peroxide Spontaneously.
Journal of the American Chemical Society
2022
Abstract
Ultrapure N2 gas was bubbled through water, and the humidified output containing undetectable concentrations of ozone filled a closed chamber in which 18 MOmega-cm water was sprayed through a silica capillary to form microdroplets. Analysis of the collected microdroplets by NMR spectroscopy showed the presence of hydrogen peroxide at a concentration level ranging from 0.3 to 1.5 muM depending on the flow conditions. This was confirmed using a spectrofluorometric assay. We suggest that this finding establishes that when sprayed to form microdroplets, water has the ability to produce hydrogen peroxide by itself. When the N2 gas is replaced by compressed air or O2 gas, the concentration of hydrogen peroxide is found to increase, indicating that gas-surface interactions with O2 in aqueous microdroplets promote the formation of hydrogen peroxide.
View details for DOI 10.1021/jacs.2c02890
View details for PubMedID 35451822
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Cooperative catalysis by a single-atom enzyme-metal complex.
Nature communications
2022; 13 (1): 2189
Abstract
Anchoring single metal atoms on enzymes has great potential to generate hybrid catalysts with high activity and selectivity for reactions that cannot be driven by traditional metal catalysts. Herein, we develop a photochemical method to construct a stable single-atom enzyme-metal complex by binding single metal atoms to the carbon radicals generated on an enzyme-polymer conjugate. The metal mass loading of Pd-anchored enzyme is up to 4.0% while maintaining the atomic dispersion of Pd. The cooperative catalysis between lipase-active site and single Pd atom accelerates alkyl-alkyl cross-coupling reaction between 1-bromohexane and B-n-hexyl-9-BBN with high efficiency (TOF is 540h-1), exceeding that of the traditional catalyst Pd(OAc)2 by a factor of 300 under ambient conditions.
View details for DOI 10.1038/s41467-022-29900-6
View details for PubMedID 35449166
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Azapodophyllotoxin Causes Lymphoma and Kidney Cancer Regression by Disrupting Tubulin and Monoglycerols.
ACS medicinal chemistry letters
2022; 13 (4): 615-622
Abstract
A natural compound screen identified several anticancer compounds, among which azapodophyllotoxin (AZP) was found to be the most potent. AZP caused decreased viability of both mouse and human lymphoma and renal cell cancer (RCC) tumor-derived cell lines. Novel AZP derivatives were synthesized and screened identifying compound NSC750212 to inhibit the growth of both lymphoma and RCC both in vitro and in vivo. A nanoimmunoassay was used to assess the NSC750212 mode of action in vivo. On the basis of the structure of AZP and its mode of action, AZP disrupts tubulin polymerization. Through desorption electrospray ionization mass spectrometry imaging, NSC750212 was found to inhibit lipid metabolism. NSC750212 suppresses monoglycerol metabolism depleting lipids and thereby inhibits tumor growth. The dual mode of tubulin polymerization disruption and monoglycerol metabolism inhibition makes NSC750212 a potent small molecule against lymphoma and RCC.
View details for DOI 10.1021/acsmedchemlett.1c00673
View details for PubMedID 35450373
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Sprayed water microdroplets containing dissolved pyridine spontaneously generate pyridyl anions.
Proceedings of the National Academy of Sciences of the United States of America
2022; 119 (12): e2200991119
Abstract
SignificanceWater microdroplets can accelerate chemical reactions by orders of magnitude compared to the same reactions in bulk water and/or trigger spontaneous reactions that do not occur in bulk solution. Among the properties of water microdroplets, the unique redox ability resulting from the spontaneous dissociation of OH- into a released electron and OH at the air-water interfaces is especially intriguing. At the air-water interface, OH- exhibits a strong reducing potential, and the resulting OH is highly oxidative, making water microdroplets a unity of opposites. We report the reduction of pyridine into pyridyl anions (C5H5N-) and the oxidation of pyridine into hydroxypyridine, which extends what we know about the redox power of water microdroplets.
View details for DOI 10.1073/pnas.2200991119
View details for PubMedID 35286201
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Succinate Accumulation Is Not Sufficient for Tumorigenesis in Mouse Chromaffin Cells But Dual Loss of SDHB and NF1 Yields SDHx-Like Pheochromocytomas
LIPPINCOTT WILLIAMS & WILKINS. 2022: E32-E33
View details for Web of Science ID 000819123700022
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Potassium Trimethylsilanolate-Promoted, Anhydrous Suzuki-Miyaura Cross-Coupling Reaction Proceeds via the "Boronate Mechanism": Evidence for the Alternative Fork in the Trail.
Journal of the American Chemical Society
2022
Abstract
Previous studies have shown that the critical transmetalation step in the Suzuki-Miyaura cross-coupling proceeds through a mechanism wherein an arylpalladium hydroxide complex reacts with an aryl boronic acid, termed the oxo-palladium pathway. Moreover, these same studies have established that the reaction between an aryl boronate and an arylpalladium halide complex (the boronate pathway) is prohibitively slow. Herein, studies on isolated intermediates, along with kinetic analysis, have demonstrated that the Suzuki-Miyaura reaction promoted by potassium trimethylsilanolate (TMSOK) proceeds through the boronate pathway, in contrast with other, established systems. Furthermore, an unprecedented, binuclear palladium(I) complex containing a mu-phenyl bridging ligand was characterized by NMR spectroscopy, mass spectrometry, and computational methods. Density functional theory (DFT) calculations suggest that the binuclear complex exhibits an open-shell ground electronic state, and reaction kinetics implicate the complex in the catalytic cycle. These results expand the breadth of potential mechanisms by which the Suzuki-Miyaura reaction can occur, and the novel binuclear palladium complex discovered has broad implications for palladium-mediated cross-coupling reactions of aryl halides.
View details for DOI 10.1021/jacs.1c08283
View details for PubMedID 35230833
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SDHB knockout and succinate accumulation are insufficient for tumorigenesis but dual SDHB/NF1 loss yields SDHx-like pheochromocytomas.
Cell reports
2022; 38 (9): 110453
Abstract
Inherited pathogenic succinate dehydrogenase (SDHx) gene mutations cause the hereditary pheochromocytoma and paraganglioma tumor syndrome. Syndromic tumors exhibit elevated succinate, an oncometabolite that is proposed to drive tumorigenesis via DNA and histone hypermethylation, mitochondrial expansion, and pseudohypoxia-related gene expression. To interrogate this prevailing model, we disrupt mouse adrenal medulla SDHB expression, which recapitulates several key molecular features of human SDHx tumors, including succinate accumulation but not 5hmC loss, HIF accumulation, or tumorigenesis. By contrast, concomitant SDHB and the neurofibromin 1 tumor suppressor disruption yields SDHx-like pheochromocytomas. Unexpectedly, invivo depletion of the 2-oxoglutarate (2-OG) dioxygenase cofactor ascorbate reduces SDHB-deficient cell survival, indicating that SDHx loss may be better tolerated by tissues with high antioxidant capacity. Contrary to the prevailing oncometabolite model, succinate accumulation and 2-OG-dependent dioxygenase inhibition are insufficient for mouse pheochromocytoma tumorigenesis, which requires additional growth-regulatory pathway activation.
View details for DOI 10.1016/j.celrep.2022.110453
View details for PubMedID 35235785
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Optimizing Coaxial Sonic Spray Geometry for Generating Water Microdroplets.
Analytical chemistry
2022
Abstract
Sonic spray creates a stream of neutral and charged microdroplets without application of voltage, heating, laser irradiation, or corona discharge. The solvent of interest flows through an inner capillary (usually constructed of fused silica) that is surrounded by an outer stainless-steel tube through which a nebulizing gas flows under pressure. This technique has been widely used as the interface in mass spectrometric studies for chemical analysis and for understanding microdroplet chemistry. We have used light scattering to characterize the size distribution and density for water microdroplets as a function of several parameters, such as water quality, water flow rate, nebulizing gas pressure, and sonic sprayer geometry. We find that the size distribution of the microdroplets, which is critical to many applications, depends most sensitively on the distance between the inner and outer capillary outlets and the gas flow pressure. The best performance as measured by the smallness of the microdroplet diameters is obtained when the gas flow pressure is the highest and there is no separation distance, d, between the two capillary outlets. In addition, at d = 0 mm, the microdroplet diameter distribution is nearly independent of the water flow rate, indicating that studies under these conditions can be scaled up.
View details for DOI 10.1021/acs.analchem.1c05337
View details for PubMedID 35191692
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Quantitative detection of hydrogen peroxide in rain, air, exhaled breath, and biological fluids by NMR spectroscopy.
Proceedings of the National Academy of Sciences of the United States of America
2022; 119 (8)
Abstract
Hydrogen peroxide (H2O2) plays a key role in environmental chemistry, biology, and medicine. H2O2 concentrations typically are 6 to 10 orders of magnitude lower than that of water, making its quantitative detection challenging. We demonstrate that optimized NMR spectroscopy allows direct, interference-free, quantitative measurements of H2O2 down to submicromolar levels in a wide range of fluids, ranging from exhaled breath and air condensate to rain, blood, urine, and saliva. NMR measurements confirm the previously reported spontaneous generation of H2O2 in microdroplets that form when condensing water vapor on a hydrophobic surface, which can interfere with atmospheric H2O2 measurements. Its antimicrobial activity and strong seasonal variation speculatively could be linked to the seasonality of respiratory viral diseases.
View details for DOI 10.1073/pnas.2121542119
View details for PubMedID 35165177
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SU086, an inhibitor of HSP90, impairs glycolysis and represents a treatment strategy for advanced prostate cancer.
Cell reports. Medicine
2022; 3 (2): 100502
Abstract
Among men, prostate cancer is the second leading cause of cancer-associated mortality, with advanced disease remaining a major clinical challenge. We describe a small molecule, SU086, as a therapeutic strategy for advanced prostate cancer. We demonstrate that SU086 inhibits the growth of prostate cancer cells invitro, cell-line and patient-derived xenografts invivo, and exvivo prostate cancer patient specimens. Furthermore, SU086 in combination with standard of care second-generation anti-androgen therapies displays increased impairment of prostate cancer cell and tumor growth invitro and invivo. Cellular thermal shift assay reveals that SU086 binds to heat shock protein 90 (HSP90) and leads to a decrease in HSP90 levels. Proteomic profiling demonstrates that SU086 binds to and decreases HSP90. Metabolomic profiling reveals that SU086 leads to perturbation of glycolysis. Our study identifies SU086 as a treatment for advanced prostate cancer as a single agent or when combined with second-generation anti-androgens.
View details for DOI 10.1016/j.xcrm.2021.100502
View details for PubMedID 35243415
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Cell-Based Ambient Venturi Autosampling and Matrix-Assisted Laser Desorption Ionization Mass Spectrometric Imaging of Secretory Products.
Analytical chemistry
2022
Abstract
A cell-based ambient Venturi autosampling device was established for the monitoring of dynamic cell secretions in response to chemical stimulations in real time with temporal resolution on the order of a second. Detection of secretory products of cells and screening of bioactive compounds are primarily performed on an ambient autosampling probe and matrix-assisted laser desorption ionization (MALDI) mass spectrometry. It takes advantage of the Venturi effect in which the fluid flowing through an inlet capillary tube is automatically fed into a parallel array of multiple outlet capillaries. Cells are incubated inside the inlet capillary tube that is connected with either a syringe pump or liquid chromatography (LC) for the transfer of single compounds or mixtures, respectively. Secretory products were continuously pushed into the outlet capillaries and then spotted into a compressed thin film of the matrix material 9-aminoacridine for MALDI mass spectrometric imaging. In physiological pH, without the use of high voltages and without the use of chemical derivatizations, this platform can be applied to the direct assay of neurotransmitters or other secretory products released from cells in response to the stimulation of individual compounds or LC-separated eluates of natural mixtures. It provides a new way to identify bioactive compounds with a detection limit down to 0.04 fmol/pixel.
View details for DOI 10.1021/acs.analchem.1c03625
View details for PubMedID 35157418
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Microdroplets can act as electrochemical cells.
The Journal of chemical physics
2022; 156 (5): 054705
Abstract
A water microdroplet in air or oil typically possesses an electric double layer (EDL) from the preferential adsorption of surface-bound ions at the periphery. We present the calculations of the ion gradients within a microdroplet at equilibrium, including systems containing buffers and water autoionization. These ion gradients are used to calculate the potential energy stored within the microdroplet. We consider how this stored potential energy can be utilized to drive chemical reactions, much like an electrochemical cell. Effective voltages as high as 111 mV are found for microdroplets having a low surface charge density (0.01 ions per nm2). Two sources of potential energy are investigated: (1) the electrostatic energy of the EDL of the microdroplet and (2) shifts in other chemical equilibria coupled to the main reaction through the EDL. A particularly important example of the latter is water autoionization, wherein the reaction of interest causes a flattening of the [H+] gradient within the EDL, resulting in a net recombination of H+ and OH- throughout the microdroplet. Numerical calculations are performed using a continuum model consisting of a balance between the electromigration and diffusion of ions throughout the microdroplet. Our treatment accounts for the autoionization of water and any chemical equilibrium of buffers present. The results are presented for uncharged water microdroplets with low amounts of salts and simple buffers in them. However, the calculational method presented here can be applied to microdroplets of any net charge, composed of any solvent, containing ions of any valence, and containing complex mixtures of chemical equilibria.
View details for DOI 10.1063/5.0078281
View details for PubMedID 35135250
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Thermal and Catalytic Decomposition of 2-Hydroxyethylhydrazine and 2-Hydroxyethylhydrazinium Nitrate Ionic Liquid.
The journal of physical chemistry. A
1800
Abstract
To develop chemical kinetics models for the combustion of ionic liquid-based monopropellants, identification of the elementary steps in the thermal and catalytic decomposition of components such as 2-hydroxyethylhydrazinium nitrate (HEHN) is needed but is currently not well understood. The first decomposition step in protic ionic liquids such as HEHN is typically the proton transfer from the cation to the anion, resulting in the formation of 2-hydroxyethylhydrazine (HEH) and HNO3. In the first part of this investigation, the high-temperature thermal decomposition of HEH is probed with flash pyrolysis (<1400 K) and vacuum ultraviolet (10.45 eV) photoionization time-of-flight mass spectrometry (VUV-PI-TOFMS). Next, the investigation into the thermal and catalytic decomposition of HEHN includes two mass spectrometric techniques: (1) tunable VUV-PI-TOFMS (7.4-15 eV) and (2) ambient ionization mass spectrometry utilizing both plasma and laser ionization techniques whereby HEHN is introduced onto a heated inert or iridium catalytic surface and the products are probed. The products can be identified by their masses, their ionization energies, and their collision-induced fragmentation patterns. Formation of product species indicates that catalytic surface recombination is an important reaction process in the decomposition mechanism of HEHN. The products and their possible elementary reaction mechanisms are discussed.
View details for DOI 10.1021/acs.jpca.1c07408
View details for PubMedID 35014846
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The perils of machine learning in designing new chemicals and materials
Nature Machine Intelligence
2022; 4: 314–315
View details for DOI 10.1038/s42256-022-00481-9
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Identification of end-stage renal disease metabolic signatures from human perspiration
Natural Sciences
2022
View details for DOI 10.1002/ntls.20220048
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Peptide and protein assays using customizable bio-affinity arrays combined with ambient ionization mass spectrometry.
Chemical science
2021; 12 (32): 10810-10816
Abstract
High-throughput identification and quantification of protein/peptide biomarkers from biofluids in a label-free manner is achieved by interfacing bio-affinity arrays (BAAs) with nano-electrospray desorption electrospray ionization mass spectrometry (nano-DESI-MS). A wide spectrum of proteins and peptides ranging from phosphopeptides to cis-diol biomolecules as well as thrombin can be rapidly extracted via arbitrarily predefined affinity interactions including coordination chemistry, covalent bonding, and biological recognition. An integrated MS platform allows continuous interrogation. Profiling and quantitation of dysregulated phosphopeptides from small-volume (∼5 μL) serum samples has been successfully demonstrated. As a front-end device adapted to any mass spectrometer, this MS platform might hold much promise in protein/peptide analysis in point-of-care (POC) diagnostics and clinical applications.
View details for DOI 10.1039/d1sc02311j
View details for PubMedID 34476062
View details for PubMedCentralID PMC8372322
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Effect of relative humidity on hydrogen peroxide production in water droplets.
QRB discovery
2021; 2: e8
Abstract
Mist is generated by ultrasonic cavitation of water (Fisher Biograde, pH 5.5-6.5) at room temperature (20-25 °C) in open air with nearly constant temperature (22-25 °C) but varying relative humidity (RH; 24-52%) over the course of many months. Water droplets in the mist are initially about 7 μm in diameter at about 50% RH. They are collected, and the concentration of hydrogen peroxide (H2O2) is measured using commercial peroxide test strips and by bromothymol blue oxidation. The quantification method is based on the Fenton chemistry of dye degradation to determine the oxidation capacity of water samples that have been treated by ultrasonication. It is found that the hydrogen peroxide concentration varies nearly linearly with RH over the range studied, reaching a low of 2 parts per million (ppm) at 24% RH and a high of 6 ppm at 52% RH. Some possible public health implications concerning the transmission of respiratory viral infections are suggested for this threefold change in H2O2 concentration with RH.
View details for DOI 10.1017/qrd.2021.6
View details for PubMedID 37529674
View details for PubMedCentralID PMC10392617
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Hydrogen-Deuterium Exchange Desorption Electrospray Ionization Mass Spectrometry Visualizes an Acidic Tumor Microenvironment.
Analytical chemistry
2021
Abstract
We report that microdroplet hydrogen-deuterium exchange (HDX) detected by desorption electrospray ionization mass spectrometry imaging (DESI-MSI) allows the measurement of the acidity of a tissue sample. The integration of HDX and DESI-MSI has been applied to visualize the acidic tumor microenvironment (TME). HDX-DESI-MSI enables the simultaneous collection of regional pH variation and its corresponding in-depth metabolomic changes. This technique is a cost-effective tool for providing insight into the pH-dependent tumor metabolism heterogeneity.
View details for DOI 10.1021/acs.analchem.1c02026
View details for PubMedID 34279072
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Peptide and protein assays using customizable bio-affinity arrays combined with ambient ionization mass spectrometry
CHEMICAL SCIENCE
2021
View details for DOI 10.1039/d1sc02311j
View details for Web of Science ID 000674275300001
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Identifying a novel glycolytic inhibitor for treatment of aggressive prostate cancer.
AMER ASSOC CANCER RESEARCH. 2021
View details for Web of Science ID 000680263506119
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A Bi-Axial Quantum State That Controls Molecular Collisions Like a Double-Slit Interferometer
FRONTIERS IN PHYSICS
2021; 9
View details for DOI 10.3389/fphy.2021.671997
View details for Web of Science ID 000660108100001
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What Role Does the Electric Double Layer Play in Redox Reactions at Planar Electrostatically Charged Insulating Surfaces?
TOPICS IN CATALYSIS
2021
View details for DOI 10.1007/s11244-021-01418-z
View details for Web of Science ID 000631801000001
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Microdroplet Ultrafast Reactions Speed Antibody Characterization.
Analytical chemistry
2021
Abstract
Recently, microdroplet reactions have aroused much interest because the microdroplet provides a unique medium where organic reactions could be accelerated by a factor of 103 or more. However, microdroplet reactions of proteins have been rarely studied. We report the occurrence of multiple-step reactions of a large protein, specifically, the digestion, reduction, and deglycosylation of an intact antibody, which can take place in microseconds with high reaction yields in aqueous microdroplets at room temperature. As a result, fast structural characterization of a monoclonal antibody, essential for assessing its quality as a therapeutic drug, can be enabled. We found that the IgG1 antibody can be digested completely by the IdeS protease in aqueous microdroplets in 250 microseconds, a 7.5 million-fold improvement in speed in comparison to traditional digestion in bulk solution (>30 min). Strikingly, inclusion of the reductant tris(2-carboxyethyl)phosphine in the spray solution caused simultaneous antibody digestion and disulfide bond reduction. Digested and reduced antibody fragments were either collected or analyzed online by mass spectrometry. Further addition of PNGase F glycosylase into the spray solution led to antibody deglycosylation, thereby producing reduced and deglycosylated fragments of analytical importance. In addition, glycated fragments of IgG1 derived from glucose modification were identified rapidly with this ultrafast digestion/reduction technique. We suggest that microdroplets can serve as powerful microreactors for both exploring large-molecule reactions and speeding their structural analyses.
View details for DOI 10.1021/acs.analchem.0c04974
View details for PubMedID 33590747
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Electrocatalytic redox neutral [3+2] annulation of N-cyclopropylanilines and alkenes
CHEMICAL SCIENCE
2021; 12 (3): 969–75
View details for DOI 10.1039/d0sc05665k
View details for Web of Science ID 000615335100015
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Shape resonance determined from angular distribution in D2 (v = 2, j = 2) + He → D2 (v = 2, j = 0) + He cold scattering.
The Journal of chemical physics
2021; 154 (10): 104309
Abstract
We find an l = 2 shape resonance fingerprinted in the angular distribution of the cold (∼1 K) Δj = 2 rotationally inelastic collision of D2 with He in a single supersonic expansion. The Stark-induced adiabatic Raman passage is used to prepare D2 in the (v = 2, j = 2) rovibrational level with control of the spatial distribution of the bond axis of the molecule by magnetic sublevel selection. We show that the rate of Δj = 2 D2-D2 relaxation is nearly two orders of magnitude weaker than that of D2-He. This suggests that the strong D2-He scattering is caused by an orbiting resonance that is highly sensitive to the shape of the long-range potential.
View details for DOI 10.1063/5.0045087
View details for PubMedID 33722006
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Quantum mechanical double slit for molecular scattering.
Science (New York, N.Y.)
2021; 374 (6570): 960-964
Abstract
[Figure: see text].
View details for DOI 10.1126/science.abl4143
View details for PubMedID 34793222
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Distinguishing between Isobaric Ions Using Microdroplet Hydrogen–Deuterium Exchange Mass Spectrometry
Metabolites
2021
View details for DOI 10.3390/metabo11110728
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In situ DESI-MSI lipidomic profiles of mucosal margin of oral squamous cell carcinoma.
EBioMedicine
2021; 70: 103529
Abstract
Although there is consensus that the optimal safe margin is ≥ 5mm, obtaining clear margins (≥5 mm) intraoperatively seems to be the major challenge. We applied a molecular diagnostic method at the lipidomic level to determine the safe surgical resection margin of OSCC by desorption electrospray ionisation mass spectrometry imaging (DESI-MSI).By overlaying mass spectrometry images with hematoxylin-eosin staining (H&E) from 18 recruited OSCC participants, the mass spectra of all pixels across the diagnosed tumour and continuous mucosal margin regions were extracted to serve as the training and validation datasets. A Lasso regression model was used to evaluate the test performance.By leave-one-out validation, the Lasso model achieved 88.6% accuracy in distinguishing between tumour and normal regions. To determine the safe surgical resection distance and margin status of OSCC, a set of 14 lipid ions that gradually decreased from tumour to normal tissue was assigned higher weight coefficients in the Lasso model. The safe surgical resection distance of OSCC was measured using the developed 14 lipid ion molecular diagnostic model for clinical reference. The overall accuracy of predicting tumours, positive margins, and negative margins was 92.6%.The spatial segmentation results based on our diagnostic model not only clearly delineated the tumour and normal tissue, but also distinguished the different status of surgical margins. Meanwhile, the safe surgical resection margin of OSCC on frozen sections can also be accurately measured using the developed diagnostic model.This study was supported by Nanjing Municipal Key Medical Laboratory Constructional Project Funding (since 2016) and the Centre of Nanjing Clinical Medicine Tumour (since 2014).
View details for DOI 10.1016/j.ebiom.2021.103529
View details for PubMedID 34391097
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A Wireless Implantable Potentiostat for Programmable Electrochemical Drug Delivery
IEEE Biomedical Circuits and Systems (BIOCAS)
2021
View details for DOI 10.1109/BioCAS49922.2021.9644991
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Ultrafast enzymatic digestion of deoxyribonucleic acid in aqueous microdroplets for sequence discrimination and identification.
QRB discovery
2021; 2: e4
Abstract
We report the use of aqueous microdroplets to accelerate deoxyribonucleic acid (DNA) fragmentation by deoxyribonuclease I (DNase I), and we present a simple, ultrafast approach named DNA fragment mass fingerprinting to discriminate different DNA sequences by comparing their fragment mass patterns. DNA fragmentation in tiny microdroplets, which was produced by electrosonically spraying (+3 kV) a room temperature aqueous solution containing 10 μM DNA and 10 μg ml-1 DNase I from a homemade setup, takes less than 1 ms. High differentiation/identification fidelity could be obtained by applying a cosine correlation measure for similarity assessment between two fragment mass patterns, which compares both mass-to-charge ratios (m/z) with an error tolerance of 5 ppm and the peaks' relative intensities. A single-nucleotide mutation in the sequence of bases, as exemplified by the sickle cell anemia mutation, is differentiated by setting a cutoff value of similarity at 90%. The order change of two adjacent bases in the sequence could still be well discriminated with a similarity of only 62% between the fragment mass patterns of the two similar sequences, which have the same molecular weights and thus cannot be differentiated by gel electrophoresis or direct mass detection by mass spectrometry. Compared to traditional genotyping methods, such as quantitative real-time polymerase chain reaction, the identification process with our approach could be completed within several minutes without any other expensive and complicated reagents or experimental steps. The potential of our approach for convenient and fast microbe genetic discrimination or identification is further demonstrated by differentiating the Orf1ab gene fragments of two similar coronaviruses with a very high sequence homologous rate of 96%, SARS-CoV-2 and bat-SL-CoVZC45, with a similarity of 0% between their fragment mass patterns.
View details for DOI 10.1017/qrd.2021.2
View details for PubMedID 34192264
View details for PubMedCentralID PMC8185430
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Introducing Nafion for In Situ Desalting and Biofluid Profiling in Spray Mass Spectrometry.
Frontiers in chemistry
2021; 9: 807244
Abstract
We introduce Nafion into the ambient ionization technique of spray mass spectrometry to serve for in situ desalting and direct analysis of biological fluids. Nafion was coated onto the surface of the triangular spray tip as the cation exchange material. Because the sulfonic group from the Nafion membrane effectively exchanges their carried protons with inorganic salt ions (e.g., Na+ and K+), the analyte's ionization efficiency can be significantly enhanced by reducing ion suppression. The desalting efficiency can reach 90% and the maximum tolerance of the absolute salt amount reaches 100 μmol. The mass spectral profile can also be simplified by removing the multiple adducted ion types from small-molecule drugs and metabolites ([M + Na]+ and [M + K]+), or multiply charged ions formed by proteins ([M + nNa]n+ and [M + nK]n+). Thus, the Nafion coating makes less ambiguous data interpretation collected from spray mass spectrometry for qualitative profiling or quantitative measurement of a target analyte.
View details for DOI 10.3389/fchem.2021.807244
View details for PubMedID 35145954
View details for PubMedCentralID PMC8821663
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Adipocytes Provide Fatty Acids to Acute Lymphoblastic Leukemia Cells.
Frontiers in oncology
2021; 11: 665763
Abstract
Background: There is increasing evidence that adipocytes play an active role in the cancer microenvironment. We have previously reported that adipocytes interact with acute lymphoblastic leukemia (ALL) cells, contributing to chemotherapy resistance and treatment failure. In the present study, we investigated whether part of this resistance is due to adipocyte provision of lipids to ALL cells.Methods: We cultured 3T3-L1 adipocytes, and tested whether ALL cells or ALL-released cytokines induced FFA release. We investigated whether ALL cells took up these FFA, and using fluorescent tagged BODIPY-FFA and lipidomics, evaluated which lipid moieties were being transferred from adipocytes to ALL. We evaluated the effects of adipocyte-derived lipids on ALL cell metabolism using a Seahorse XF analyzer and expression of enzymes important for lipid metabolism, and tested whether these lipids could protect ALL cells from chemotherapy. Finally, we evaluated a panel of lipid synthesis and metabolism inhibitors to determine which were affected by the presence of adipocytes.Results: Adipocytes release free fatty acids (FFA) when in the presence of ALL cells. These FFA are taken up by the ALL cells and incorporated into triglycerides and phospholipids. Some of these lipids are stored in lipid droplets, which can be utilized in states of fuel deprivation. Adipocytes preferentially release monounsaturated FFA, and this can be attenuated by inhibiting the desaturating enzyme steroyl-CoA decarboxylase-1 (SCD1). Adipocyte-derived FFA can relieve ALL cell endogenous lipogenesis and reverse the cytotoxicity of pharmacological acetyl-CoA carboxylase (ACC) inhibition. Further, adipocytes alter ALL cell metabolism, shifting them from glucose to FFA oxidation. Interestingly, the unsaturated fatty acid, oleic acid, protects ALL cells from modest concentrations of chemotherapy, such as those that might be present in the ALL microenvironment. In addition, targeting lipid synthesis and metabolism can potentially reverse adipocyte protection of ALL cells.Conclusion: These findings uncover a previously unidentified interaction between ALL cells and adipocytes, leading to transfer of FFA for use as a metabolic fuel and macromolecule building block. This interaction may contribute to ALL resistance to chemotherapy, and could potentially be targeted to improve ALL treatment outcome.
View details for DOI 10.3389/fonc.2021.665763
View details for PubMedID 33968771
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MassExplorer: a computational tool for analyzing desorption electrospray ionization mass spectrometry data
Bioinformatics (Oxford, England)
2021
Abstract
High-throughput gene expression can be used to address a wide range of fundamental biological problems, but datasets of an appropriate size are often unavailable. Moreover, existing transcriptomics simulators have been criticised because they fail to emulate key properties of gene expression data. In this paper, we develop a method based on a conditional generative adversarial network to generate realistic transcriptomics data for E. coli and humans. We assess the performance of our approach across several tissues and cancer types.We show that our model preserves several gene expression properties significantly better than widely used simulators such as SynTReN or GeneNetWeaver. The synthetic data preserves tissue and cancer-specific properties of transcriptomics data. Moreover, it exhibits real gene clusters and ontologies both at local and global scales, suggesting that the model learns to approximate the gene expression manifold in a biologically meaningful way.Code is available at: https://github.com/rvinas/adversarial-gene-expression.Supplementary data are available at Bioinformatics online.
View details for DOI 10.1093/bioinformatics/btab282
View details for PubMedID 34009252
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Accelerated Oxidation of Organic Sulfides by Microdroplet Chemistry.
The Journal of organic chemistry
2021
Abstract
We report the rapid oxidation of organic sulfides to sulfoxides by means of microdroplet chemistry at room temperature using a spray solution containing an organic sulfide dissolved in water/methanol, dilute (11%-14%) sodium hypochlorite (NaClO), and 5% chloroauric acid (HAuCl4). Ultrasonic nebulization, easy ambient sonic-spray ionization, or electrosonic spray ionization serves as the microdroplet source. High-resolution mass spectrometry was used as an online detector, and nuclear magnetic resonance was used as an offline detector. We found that the sulfoxide yields vary between 66 and 95%, the highest rate of product formation is 195 mg/min for benzyl phenyl sulfoxide, and the time required is a few minutes, which is much less than that required for the conventional means of achieving this chemical transformation. We also applied this microdroplet method to protein fingerprinting. We found that protein sequences containing methionine can be quickly oxidized, providing useful information for protein structure determinations.
View details for DOI 10.1021/acs.joc.0c02942
View details for PubMedID 33656874
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Condensing water vapor to droplets generates hydrogen peroxide.
Proceedings of the National Academy of Sciences of the United States of America
2020
Abstract
It was previously shown [J. K. Lee et al., Proc. Natl. Acad. Sci. U.S.A, 116, 19294-19298 (2019)] that hydrogen peroxide (H2O2) is spontaneously produced in micrometer-sized water droplets (microdroplets), which are generated by atomizing bulk water using nebulization without the application of an external electric field. Here we report that H2O2 is spontaneously produced in water microdroplets formed by dropwise condensation of water vapor on low-temperature substrates. Because peroxide formation is induced by a strong electric field formed at the water-air interface of microdroplets, no catalysts or external electrical bias, as well as precursor chemicals, are necessary. Time-course observations of the H2O2 production in condensate microdroplets showed that H2O2 was generated from microdroplets with sizes typically less than 10 m. The spontaneous production of H2O2 was commonly observed on various different substrates, including silicon, plastic, glass, and metal. Studies with substrates with different surface conditions showed that the nucleation and the growth processes of condensate water microdroplets govern H2O2 generation. We also found that the H2O2 production yield strongly depends on environmental conditions, including relative humidity and substrate temperature. These results show that the production of H2O2 occurs in water microdroplets formed by not only atomizing bulk water but also condensing water vapor, suggesting that spontaneous water oxidation to form H2O2 from water microdroplets is a general phenomenon. These findings provide innovative opportunities for green chemistry at heterogeneous interfaces, self-cleaning of surfaces, and safe and effective disinfection. They also may have important implications for prebiotic chemistry.
View details for DOI 10.1073/pnas.2020158117
View details for PubMedID 33229543
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Electrocatalytic redox neutral [3 + 2] annulation of N-cyclopropylanilines and alkenes.
Chemical science
2020; 12 (3): 969-975
Abstract
Although synthetic organic electrochemistry (EC) has advanced significantly, net redox neutral electrosynthesis is quite rare. Two approaches have been employed to achieve this type of electrosynthesis. One relies on turnover of the product by the reactant in a chain mechanism. The other involves both oxidation on the anode and reduction on the cathode in which the radical cation or the radical anion of the product has to migrate between two electrodes. Herein, a home-built electrochemistry/mass spectrometry (EC/MS) platform was used to generate an N-cyclopropylaniline radical cation electrochemically and to monitor its reactivity toward alkenes by mass spectrometry (MS), which led to the discovery of a new redox neutral reaction of intermolecular [3 + 2] annulation of N-cyclopropylanilines and alkenes to provide an aniline-substituted 5-membered carbocycle via direct electrolysis (yield up to 81%). A chain mechanism, involving the regeneration of the substrate radical cation and the formation of the neutral product, is shown to be responsible for promoting such a redox neutral annulation reaction, as supported by experimental evidence of EC/MS.
View details for DOI 10.1039/d0sc05665k
View details for PubMedID 34163863
View details for PubMedCentralID PMC8179209
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Coulometry-assisted quantitation in spray ionization mass spectrometry
JOURNAL OF MASS SPECTROMETRY
2020
View details for DOI 10.1002/jms.4628
View details for Web of Science ID 000559900100001
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Mechanistic Study of Isotactic Poly(propylene oxide) Synthesis using a Tethered Bimetallic Chromium Salen Catalyst
ACS CATALYSIS
2020; 10 (15): 8960–67
View details for DOI 10.1021/acscatal.0c02135
View details for Web of Science ID 000562075000085
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Mechanistic Study of Isotactic Poly(propylene oxide) Synthesis using a Tethered Bimetallic Chromium Salen Catalyst.
ACS catalysis
2020; 10 (15): 8960-8967
Abstract
Initial catalyst dormancy has been mitigated for the enantioselective polymerization of propylene oxide using a tethered bimetallic chromium(III) salen complex. A detailed mechanistic study provided insight into the species responsible for this induction period and guided efforts to remove them. High-resolution electrospray ionization-mass spectrometry and density functional theory computations revealed that a μ-hydroxide and a bridged 1,2-hydroxypropanolate complex are present during the induction period. Kinetic studies and additional computation indicated that the μ-hydroxide complex is a short-lived catalyst arrest state, where hydroxide dissociation from one metal allows for epoxide enchainment to form the 1,2-hydroxypropanolate arrest state. While investigating anion dependence on the induction period, it became apparent that catalyst activation was the main contributor for dormancy. Using a 1,2-diol or water as chain transfer agents (CTAs) led to longer induction periods as a result of increased 1,2-hydroxyalkanolate complex formation. With a minor catalyst modification, rigorous drying conditions, and avoiding 1,2-diols as CTAs, the induction period was essentially removed.
View details for DOI 10.1021/acscatal.0c02135
View details for PubMedID 34367720
View details for PubMedCentralID PMC8345319
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Spraying Small Water Droplets Acts as a Bacteriocide.
QRB discovery
2020; 1: e3
Abstract
Disinfectants are important for arresting the spread of pathogens in the environment. Frequently used disinfectants are often incompatible with certain surfaces, expensive and can produce hazardous by-products. We report that micron-sized water droplets can act as an effective disinfectant, which were formed by spraying pure bulk water with coaxial nebulizing airflow. Spraying for 20 min onto Escherichia coli and Salmonella typhimurium on stainless-steel discs caused inactivation of over 98% of the bacteria. Control experiments resulted in less than 10% inactivation (water stream only and gas only) and 55% inactivation with 3% hydrogen peroxide. Experiments have shown that cell death results from cell wall destruction. We suggest that the combined action of reactive oxygen species present in water droplets (but not in bulk water) along with the droplet surface charge is responsible for the observed bactericidal activity.
View details for DOI 10.1017/qrd.2020.2
View details for PubMedID 37528962
View details for PubMedCentralID PMC10392691
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Coulometry-assisted quantitation in spray ionization mass spectrometry.
Journal of mass spectrometry : JMS
2020: e4628
Abstract
The concentration of target analyte in a mixture can be quantified by combining coulometric measurements with spray ionization mass spectrometry. A three-electrode system screen printed on the polymer support acts both as the coulometry platform for electrochemical oxidation and the sample loading tip for spray ionization. After loading a droplet of the analyte solution onto the tip, two steps were taken to implement quantitation. First, the electrochemical oxidation potential was optimized with cyclic voltammetry followed by coulometric measurements to calculate the amount of oxidized analyte under a constant low voltage within a fixed period of time (5 s). Then, a high voltage (+4.5 kV) was applied to the tip to trigger spray ionization for measuring the oxidation yield from the native analyte ion and its oxidized product ion intensities by mass spectrometry. The analyte's native concentration is quantified by dividing the oxidized product's concentration (based on Coulomb's law) and the oxidation yield (estimated from mass spectrometry [MS] assuming that the parent and oxidation product have nearly the same ionization efficiencies). The workflow has an advantage in being free of any standard for constructing the quantitation curve. Several model compounds (tyrosine, dopamine, and angiotensin II) were selected for method validation. It was demonstrated that this strategy was feasible with an accuracy of ~15% for a wide coverage of different species including endogenous metabolites and peptides. As an example of its possible practical use, it was initially employed to make a bilirubin assay in urine.
View details for DOI 10.1002/jms.4628
View details for PubMedID 33245185
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Strong, Nonresonant Radiation Enhances Cis-Trans Photoisomerization of Stilbene in Solution.
The journal of physical chemistry. A
2020
Abstract
Previously, it has been demonstrated that external electric fields may be used to exert control over chemical reactivity. In this study, the impact of a strong, nonresonant IR field (1064 nm) on the photoisomerization of cis-stilbene is investigated in cyclohexane solution. The design of a suitable reaction vessel for characterization of this effect is presented. The electric field supplied by the pulsed, near-IR radiation (epsilonl = 4.5 * 107 V/cm) enhances the cis trans photoisomerization yield at the red edge of the absorption spectrum (wavelengths between 337 and 340 nm). Within the microliter focal volume, up to 75% of all cis-stilbene molecules undergo isomerization to trans-stilbene in the strong electric-field environment, indicating a significant increase relative to the 35% yield of trans-stilbene under field-free conditions. This result correlates with a 1-3% enhancement in the trans-stilbene concentration throughout the bulk solution. Theoretical analysis suggests that the observed change is the result of dynamic Stark shifting of the ground and first excited states, leading to a significant redshift in cis-stilbene's absorption spectrum. The predicted increase in the absorption cross section in this range of excitation wavelengths is qualitatively consistent with the experimental increase in trans-stilbene production.
View details for DOI 10.1021/acs.jpca.0c02732
View details for PubMedID 32585098
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Oral squamous cell carcinoma diagnosed from saliva metabolic profiling.
Proceedings of the National Academy of Sciences of the United States of America
2020
Abstract
Saliva is a noninvasive biofluid that can contain metabolite signatures of oral squamous cell carcinoma (OSCC). Conductive polymer spray ionization mass spectrometry (CPSI-MS) is employed to record a wide range of metabolite species within a few seconds, making this technique appealing as a point-of-care method for the early detection of OSCC. Saliva samples from 373 volunteers, 124 who are healthy, 124 who have premalignant lesions, and 125 who are OSCC patients, were collected for discovering and validating dysregulated metabolites and determining altered metabolic pathways. Metabolite markers were reconfirmed at the primary tissue level by desorption electrospray ionization MS imaging (DESI-MSI), demonstrating the reliability of diagnoses based on saliva metabolomics. With the aid of machine learning (ML), OSCC and premalignant lesions can be distinguished from the normal physical condition in real time with an accuracy of 86.7%, on a person by person basis. These results suggest that the combination of CPSI-MS and ML is a feasible tool for accurate, automated diagnosis of OSCC in clinical practice.
View details for DOI 10.1073/pnas.2001395117
View details for PubMedID 32601197
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Author Correction: Optimization of Molecules via Deep Reinforcement Learning.
Scientific reports
2020; 10 (1): 10478
Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
View details for DOI 10.1038/s41598-020-66840-x
View details for PubMedID 32572065
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Erratum: "HD (v = 1, j = 2, m) orientation controls HD-He rotationally inelastic scattering near 1 K" [J. Chem. Phys. 150, 174301 (2019)].
The Journal of chemical physics
2020; 152 (20): 209901
View details for DOI 10.1063/5.0012127
View details for PubMedID 32486689
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Highly parallel and efficient single cell mRNA sequencing with paired picoliter chambers.
Nature communications
2020; 11 (1): 2118
Abstract
ScRNA-seq has the ability to reveal accurate and precise cell types and states. Existing scRNA-seq platforms utilize bead-based technologies uniquely barcoding individual cells, facing practical challenges for precious samples with limited cell number. Here, we present a scRNA-seq platform, named Paired-seq, with high cells/beads utilization efficiency, cell-free RNAs removal capability, high gene detection ability and low cost. We utilize the differential flow resistance principle to achieve single cell/barcoded bead pairing with high cell utilization efficiency (95%). The integration of valves and pumps enables the complete removal of cell-free RNAs, efficient cell lysis and mRNA capture, achieving highest mRNA detection accuracy (R=0.955) and comparable sensitivity. Lower reaction volume and higher mRNA capture and barcoding efficiency significantly reduce the cost of reagents and sequencing. The single-cell expression profile of mES and drug treated cells reveal cell heterogeneity, demonstrating the enormous potential of Paired-seq for cell biology, developmental biology and precision medicine.
View details for DOI 10.1038/s41467-020-15765-0
View details for PubMedID 32355211
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Spraying Model PAHs on a Charged TiO2 Surface for High-Efficiency Degradation
ENERGY & FUELS
2020; 34 (4): 4289–95
View details for DOI 10.1021/acs.energyfuels.0c00068
View details for Web of Science ID 000526324100029
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Unusual Properties of Water at Heterogeneous Biological Interfaces
CELL PRESS. 2020: 476A
View details for Web of Science ID 000513023203132
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Nanoparticles decorated with granulocyte-colony stimulating factor for targeting myeloid cells.
Nanoscale
2020
Abstract
Dysregulated myeloid cell activity underlies a variety of pathologies, including immunosuppression in malignant cancers. Current treatments to alter myeloid cell behavior also alter other immune cell subpopulations and nonimmune cell types with deleterious side effects. Therefore, improved selectivity of myeloid treatment is an urgent need. To meet this need, we demonstrate a novel, targeted nanoparticle system that achieves superior myeloid selectivity both in vitro and in vivo. This system comprises: (1) granulocyte-colony stimulating factor (G-CSF) as a targeting ligand to promote accumulation in myeloid cells, including immunosuppressive myeloid-derived suppressor cells (MDSCs); (2) albumin nanoparticles 100-120 nm in diameter that maintain morphology and drug payload in simulated physiological conditions; and (3) a fluorophore that enables nanoparticle tracking and models a therapeutic molecule. Here, we show that this strategy achieves high myeloid uptake in mixed primary immune cells and that nanoparticles successfully infiltrate the 4T1 triple-negative breast tumor murine microenvironment, where they preferentially accumulate in myeloid cells in a mouse model. Further development will realize diagnostic myeloid cell tracking applications and therapeutic delivery of myeloid-reprogramming drugs.
View details for DOI 10.1039/c9nr06494j
View details for PubMedID 31956862
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Metabolite therapy guided by liquid biopsy proteomics delays retinal neurodegeneration.
EBioMedicine
2020; 52: 102636
Abstract
Neurodegenerative diseases are incurable disorders caused by progressive neuronal cell death. Retinitis pigmentosa (RP) is a blinding neurodegenerative disease that results in photoreceptor death and progresses to the loss of the entire retinal network. We previously found that proteomic analysis of the adjacent vitreous served as way to indirectly biopsy the retina and identify changes in the retinal proteome.We analyzed protein expression in liquid vitreous biopsies from autosomal recessive (ar)RP patients with PDE6A mutations and arRP mice with Pde6ɑ mutations. Proteomic analysis of retina and vitreous samples identified molecular pathways affected at the onset of photoreceptor death. Based on affected molecular pathways, arRP mice were treated with a ketogenic diet or metabolites involved in fatty-acid synthesis, oxidative phosphorylation, and the tricarboxylic acid (TCA) cycle.Dietary supplementation of a single metabolite, ɑ-ketoglutarate, increased docosahexaeonic acid levels, provided neuroprotection, and enhanced visual function in arRP mice. A ketogenic diet delayed photoreceptor cell loss, while vitamin B supplementation had a limited effect. Finally, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) on ɑ-ketoglutarate-treated mice revealed restoration of metabolites that correlated with our proteomic findings: uridine, dihydrouridine, and thymidine (pyrimidine and purine metabolism), glutamine and glutamate (glutamine/glutamate conversion), and succinic and aconitic acid (TCA cycle).This study demonstrates that replenishing TCA cycle metabolites via oral supplementation prolongs retinal function and provides a neuroprotective effect on the photoreceptor cells and inner retinal network.NIH grants [R01EY026682, R01EY024665, R01EY025225, R01EY024698, R21AG050437, P30EY026877, 5P30EY019007, R01EY018213, F30EYE027986, T32GM007337, 5P30CA013696], NSF grant CHE-1734082.
View details for DOI 10.1016/j.ebiom.2020.102636
View details for PubMedID 32028070
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CONCENTRATION GRADIENTS INSIDE MICRODROPLETS.
Micro total analysis systems : proceedings of the ... [Mu] TAS International Conference on Miniaturized Chemical and Biochemical Analysis Systems. [Mu] TAS (Conference)
2020; 2020: 212-213
Abstract
Small water microdroplets in microfluidic systems have a high surface charge density resulting from charged surfactants. As a result, an electric double layer forms inside the droplet. Depletion of ions from the center of the droplet to form the double layer can shift the concentration of ions dramatically from that of the microdroplet precursor solution. Here we show numerical solutions to the Gouy-Chapman model in spherical coordinates. Some notable effects include: 1) large percentages of the microdroplet volume experience very large DC electric fields; 2) many ions get forced into a Stern layer giving dramatically different conditions from the bulk.
View details for PubMedID 34557061
View details for PubMedCentralID PMC8457253
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Strong Electric Field Observed at the Interface of Aqueous Microdroplets.
The journal of physical chemistry letters
2020: 7423–28
Abstract
Chemical reactions in aqueous microdroplets often exhibit unusual kinetic and thermodynamic properties not observed in bulk solution. While an electric field has been implicated at the water interface, there has been no direct measurement in aqueous microdroplets, largely due to the lack of proper measurement tools. Herein, we employ newly developed stimulated Raman excited fluorescence microscopy to measure the electric field at the water-oil interface of microdroplets. As determined by the vibrational Stark effect of a nitrile-bearing fluorescent probe, the strength of the electric field is found to be on the order of 107 V/cm. This strong electric field aligns probe dipoles with respect to the interface. The formation of the electric field likely arises from charge separation caused by the adsorption of negative ions at the water-oil interface of microdroplets. We suggest that this strong electric field might account in part for the unique properties of chemical reactions reported in microdroplets.
View details for DOI 10.1021/acs.jpclett.0c02061
View details for PubMedID 32804510
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Simple model for the electric field and spatial distribution of ions in a microdroplet.
The Journal of chemical physics
2020; 152 (18): 184702
Abstract
It is well established that the chemistry in microdroplets has been found to be radically different from reactions in bulk, particularly in the case of water. It has also been established that there is a threshold size for microdroplets to behave differently than droplets near the 10 µm diameter range. We present a three-dimensional electrostatic treatment in the spirit of the Gouy-Chapman model for double layers at interfaces. Our treatment predicts a strong concentration of charged molecules toward the surface of the droplet. As the droplet size deceases, the majority of the volume of the liquid experiences a large DC electric field. Such electric fields are highly unusual in a conducting fluid such as water. We believe that this unique environment helps to explain the reaction rate acceleration and new chemistry that have been observed in microdroplets compared to bulk phase.
View details for DOI 10.1063/5.0006550
View details for PubMedID 32414270
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Effects of Weak Electrolytes on Electric Double Layer Ion Distributions.
The journal of physical chemistry letters
2020: 8302–6
Abstract
Many common experimental systems have electric double layers containing weak electrolytes, including systems with buffers. The pH at the boundary of the diffuse layer is an important parameter for determining the physicochemical state of the system, including surface charge density. We show that the Boltzmann equilibrium relation can be used as an exact solution for weak electrolyte electric double layers. Using these results, we provide a closed-form relation for the maximum pH change in a buffered electric double layer, in terms of the boundary potential. Importantly, our results suggest that equilibrium electric double layer concepts developed for strong electrolytes can be expanded to include weak electrolytes.
View details for DOI 10.1021/acs.jpclett.0c02247
View details for PubMedID 32915583
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Restricted Intramolecular Rotation of Fluorescent Molecular Rotors at the Periphery of Aqueous Microdroplets in Oil
Scientific Reports
2020; 10
View details for DOI 10.1038/s41598-020-73980-7
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Strong Concentration Enhancement of Molecules at the Interface of Aqueous Microdroplets
The Journal of Physical Chemistry B
2020
View details for DOI 10.1021/acs.jpcb.0c07718
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Spatial localization of charged molecules by salt ions in oil-confined water microdroplets.
Science advances
2020; 6 (41)
Abstract
Cells contain more than 100 mM salt ions that are typically confined to dimensions of 5 to 10 micrometers by a hydrophobic cellular membrane. We found that in aqueous microdroplets having the same size as cells and that are confined in hydrocarbon oil, negatively charged molecules were distributed rather uniformly over the interior of the microdroplet, whereas positively charged molecules were localized at and near the surface. However, the addition of salt (NaCl) to the microdroplet caused all charged molecules to be localized near the oil-water interface. This salt-induced relocalization required less salt concentration in microdroplets compared to bulk water. Moreover, the localization became more prominent as the size of the microdroplet was reduced. The relocatization also critically depended on the type of oil. Our results imply that salt ions and different hydrophobic interfaces together may govern the local distribution of charged biomolecules in confined intracellular environments.
View details for DOI 10.1126/sciadv.aba0181
View details for PubMedID 33028513
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Cell-Type-Specific Metabolic Profiling Achieved by Combining Desorption Electrospray Ionization Mass Spectrometry Imaging and Immunofluorescence Staining.
Analytical chemistry
2020
Abstract
Cell-type-specific metabolic profiling in tissue with heterogeneous composition has been of great interest across all mass spectrometry imaging (MSI) technologies. We report here a powerful new chemical imaging capability in desorption electrospray ionization (DESI) MSI, which enables cell-type-specific and in situ metabolic profiling in complex tissue samples. We accomplish this by combining DESI-MSI with immunofluorescence staining using specific cell-type markers. We take advantage of the variable frequency of each distinct cell type in the lateral septal nucleus (LSN) region of mouse forebrain. This allows computational deconvolution of the cell-type-specific metabolic profile in neurons and astrocytes by convex optimization-a machine learning method. Based on our approach, we observed 107 metabolites that show different distributions and intensities between astrocytes and neurons. We subsequently identified 23 metabolites using high-resolution mass spectrometry (MS) and tandem MS, which include small metabolites such as adenosine and N-acetylaspartate previously associated with astrocytes and neurons, respectively, as well as accumulation of several phospholipid species in neurons which have not been studied before. Overall, this method overcomes the relatively low spatial resolution of DESI-MSI and provides a new platform for in situ metabolic investigation at the cell-type level in complex tissue samples with heterogeneous cell-type composition.
View details for DOI 10.1021/acs.analchem.0c02519
View details for PubMedID 32880432
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Harnessing the Power of Adiabatic Curve Crossing to Populate the Highly Vibrationally Excited H_{2} (v=7, j=0) Level.
Physical review letters
2020; 124 (16): 163202
Abstract
A large ensemble of ∼10^{9} H_{2} (v=7, j=0) molecules is prepared in the collision-free environment of a supersonic beam by transferring nearly the entire H_{2} (v=0, j=0) ground-state population, where v and j are the vibrational and rotational quantum numbers, respectively. This is accomplished by controlling the crossing of the optically dressed adiabatic states using a pair of phase coherent laser pulses. The preparation of highly vibrationally excited H_{2} molecules opens new opportunities to test fundamental physical principles using two loosely bound yet entangled H atoms.
View details for DOI 10.1103/PhysRevLett.124.163202
View details for PubMedID 32383909
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Aqueous microdroplets containing only ketones or aldehydes undergo Dakin and Baeyer-Villiger reactions.
Chemical science
2019; 10 (48): 10974-10978
Abstract
The Dakin and Baeyer-Villiger (BV) oxidation reactions require addition of peroxides as oxidants and an acid or a base as a catalyst. Reaction times range from hours to days to obtain target products. Previously, we reported that hydrogen peroxide (H2O2) is spontaneously generated in water microdroplets without any added chemicals or applied electrical potential. Here, we report that the Dakin and BV reactions occur in modest yields within milliseconds in aqueous microdroplets at room-temperature without the addition of external peroxides and catalysts. H2O2 generation is the result of the special environment of the microdroplet surface, which promotes water autoionization. We find that increasing the content of water and decreasing the droplet size improve the product yield of the Dakin and BV reactions, supporting the contention that the amount of H2O2 generated in aqueous microdroplets could induce the two reactions and the reactions occur at or near the air-water interface of the microdroplet surface.
View details for DOI 10.1039/c9sc05112k
View details for PubMedID 32874488
View details for PubMedCentralID PMC7439776
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Identification of Diagnostic Metabolic Signatures in Clear Cell Renal Cell Carcinoma Using Mass Spectrometry Imaging.
International journal of cancer
2019
Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common and lethal subtype of kidney cancer. Intraoperative frozen section (IFS) analysis is used to confirm the diagnosis during partial nephrectomy (PN). However, surgical margin evaluation using IFS analysis is time consuming and unreliable, leading to relatively low utilization. In this study, we demonstrated the use of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) as a molecular diagnostic and prognostic tool for ccRCC. DESI-MSI was conducted on fresh-frozen 23 normal-tumor paired nephrectomy specimens of ccRCC. An independent validation cohort of 17 normal-tumor pairs were analyzed. DESI-MSI provides two-dimensional molecular images of tissues with mass spectra representing small metabolites, fatty acids, and lipids. These tissues were subjected to histopathologic evaluation. A set of metabolites that distinguish ccRCC from normal kidney were identified by performing least absolute shrinkage and selection operator (Lasso) and log-ratio Lasso analysis. Lasso analysis with leave-one-patient-out cross validation selected 57 peaks from over 27,000 metabolic features across 37,608 pixels obtained using DESI-MSI of ccRCC and normal tissues. Baseline Lasso of metabolites predicted the class of each tissue to be normal or cancerous tissue with an accuracy of 94% and 76%, respectively. Combining the baseline Lasso with the ratio of glucose to arachidonic acid could potentially reduce scan time and improve accuracy to identify normal (82%) and ccRCC (88%) tissue. DESI-MSI allows rapid detection of metabolites associated with normal and ccRCC with high accuracy. As this technology advances, it could be used for rapid intraoperative assessment of surgical margin status. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/ijc.32843
View details for PubMedID 31863456
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Proof of concept for identifying cystic fibrosis from perspiration samples.
Proceedings of the National Academy of Sciences of the United States of America
2019
Abstract
The gold standard for cystic fibrosis (CF) diagnosis is the determination of chloride concentration in sweat. Current testing methodology takes up to 3 h to complete and has recognized shortcomings on its diagnostic accuracy. We present an alternative method for the identification of CF by combining desorption electrospray ionization mass spectrometry and a machine-learning algorithm based on gradient boosted decision trees to analyze perspiration samples. This process takes as little as 2 min, and we determined its accuracy to be 98 ± 2% by cross-validation on analyzing 277 perspiration samples. With the introduction of statistical bootstrap, our method can provide a confidence estimate of our prediction, which helps diagnosis decision-making. We also identified important peaks by the feature selection algorithm and assigned the chemical structure of the metabolites by high-resolution and/or tandem mass spectrometry. We inspected the correlation between mild and severe CFTR gene mutation types and lipid profiles, suggesting a possible way to realize personalized medicine with this noninvasive, fast, and accurate method.
View details for DOI 10.1073/pnas.1909630116
View details for PubMedID 31740593
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Spontaneous generation of hydrogen peroxide from aqueous microdroplets.
Proceedings of the National Academy of Sciences of the United States of America
2019
Abstract
We show H2O2 is spontaneously produced from pure water by atomizing bulk water into microdroplets (1 mum to 20 m in diameter). Production of H2O2, as assayed by H2O2-sensitve fluorescence dye peroxyfluor-1, increased with decreasing microdroplet size. Cleavage of 4-carboxyphenylboronic acid and conversion of phenylboronic acid to phenols in microdroplets further confirmed the generation of H2O2 The generated H2O2 concentration was 30 M (1 part per million) as determined by titration with potassium titanium oxalate. Changing the spray gas to O2 or bubbling O2 decreased the yield of H2O2 in microdroplets, indicating that pure water microdroplets directly generate H2O2 without help from O2 either in air surrounding the droplet or dissolved in water. We consider various possible mechanisms for H2O2 formation and report a number of different experiments exploring this issue. We suggest that hydroxyl radical (OH) recombination is the most likely source, in which OH is generated by loss of an electron from OH- at or near the surface of the water microdroplet. This catalyst-free and voltage-free H2O2 production method provides innovative opportunities for green production of hydrogen peroxide.
View details for DOI 10.1073/pnas.1911883116
View details for PubMedID 31451646
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Using DESI-MSI to identify the genetic basis and tumorigenic mechanism of pheochromocytomas
AMER CHEMICAL SOC. 2019
View details for Web of Science ID 000525055501165
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Photon-catalyzed photoisomerization of stilbene
AMER CHEMICAL SOC. 2019
View details for Web of Science ID 000525055501162
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On-demand drug release from polypyrrole nanoparticulate films
AMER CHEMICAL SOC. 2019
View details for Web of Science ID 000525055501160
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Detecting bacteria using an artificial antibody
AMER CHEMICAL SOC. 2019
View details for Web of Science ID 000525055501173
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Oncogene MYC regulates lipogenesis essential for neoplastic growth
AMER CHEMICAL SOC. 2019
View details for Web of Science ID 000525055501180
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The MYC Oncogene Cooperates with Sterol-Regulated Element-Binding Protein to Regulate Lipogenesis Essential for Neoplastic Growth.
Cell metabolism
2019
Abstract
Lipid metabolism is frequently perturbed in cancers, but the underlying mechanism is unclear. We present comprehensive evidence that oncogene MYC, in collaboration with transcription factor sterol-regulated element-binding protein (SREBP1), regulates lipogenesis to promote tumorigenesis. We used human and mouse tumor-derived cell lines, tumor xenografts, and four conditional transgenic mouse models of MYC-induced tumors to show that MYC regulates lipogenesis genes, enzymes, and metabolites. We found that MYC induces SREBP1, and they collaborate to activate fatty acid (FA) synthesis and drive FA chain elongation from glucose and glutamine. Further, by employing desorption electrospray ionization mass spectrometry imaging (DESI-MSI), we observed invivo lipidomic changes upon MYC induction across different cancers, for example, aglobal increase in glycerophosphoglycerols. After inhibition of FA synthesis, tumorigenesis was blocked, and tumors regressed in both xenograft and primary transgenic mouse models, revealing the vulnerability of MYC-induced tumors to the inhibition of lipogenesis.
View details for DOI 10.1016/j.cmet.2019.07.012
View details for PubMedID 31447321
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Early detection of unilateral ureteral obstruction by desorption electrospray ionization mass spectrometry.
Scientific reports
2019; 9 (1): 11007
Abstract
Desorption electrospray ionization mass spectrometry (DESI-MS) is an emerging analytical tool for rapid in situ assessment of metabolomic profiles on tissue sections without tissue pretreatment or labeling. We applied DESI-MS to identify candidate metabolic biomarkers associated with kidney injury at the early stage. DESI-MS was performed on sections of kidneys from 80 mice over a time course following unilateral ureteral obstruction (UUO) and compared to sham controls. A predictive model of renal damage was constructed using the LASSO (least absolute shrinkage and selection operator) method. Levels of lipid and small metabolites were significantly altered and glycerophospholipids comprised a significant fraction of altered species. These changes correlate with altered expression of lipid metabolic genes, with most genes showing decreased expression. However, rapid upregulation of PG(22:6/22:6) level appeared to be a hitherto unknown feature of the metabolic shift observed in UUO. Using LASSO and SAM (significance analysis of microarrays), we identified a set of well-measured metabolites that accurately predicted UUO-induced renal damage that was detectable by 12h after UUO, prior to apparent histological changes. Thus, DESI-MS could serve as a useful adjunct to histology in identifying renal damage and demonstrates early and broad changes in membrane associated lipids.
View details for DOI 10.1038/s41598-019-47396-x
View details for PubMedID 31358807
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Optimization of Molecules via Deep Reinforcement Learning.
Scientific reports
2019; 9 (1): 10752
Abstract
We present a framework, which we call Molecule Deep Q-Networks (MolDQN), for molecule optimization by combining domain knowledge of chemistry and state-of-the-art reinforcement learning techniques (double Q-learning and randomized value functions). We directly define modifications on molecules, thereby ensuring 100% chemical validity. Further, we operate without pre-training on any dataset to avoid possible bias from the choice of that set. MolDQN achieves comparable or better performance against several other recently published algorithms for benchmark molecular optimization tasks. However, we also argue that many of these tasks are not representative of real optimization problems in drug discovery. Inspired by problems faced during medicinal chemistry lead optimization, we extend our model with multi-objective reinforcement learning, which maximizes drug-likeness while maintaining similarity to the original molecule. We further show the path through chemical space to achieve optimization for a molecule to understand how the model works.
View details for DOI 10.1038/s41598-019-47148-x
View details for PubMedID 31341196
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Photon catalysis of deuterium iodide photodissociation
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
2019; 21 (26): 14195–204
View details for DOI 10.1039/c8cp06107f
View details for Web of Science ID 000474136100030
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The CM carbonaceous chondrite regolith Diepenveen
METEORITICS & PLANETARY SCIENCE
2019; 54 (7): 1431–61
View details for DOI 10.1111/maps.13297
View details for Web of Science ID 000478847500003
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Micrometer-Sized Water Droplets Induce Spontaneous Reduction.
Journal of the American Chemical Society
2019
Abstract
Bulk water serves as an inert solvent for many chemical and biological reactions. Here, we report a striking exception. We observe that in micrometer-sized water droplets (microdroplets), spontaneous reduction of several organic molecules occurs, pyruvate to lactate, lipoic acid to dihydrolipoic acid, fumarate to succinate, and oxaloacetate to malate. This reduction proceeds in microdroplets without any added electron donors or acceptors and without any applied voltage. In three of the four cases, the reduction efficiency is 90% or greater when the concentration of the dissolved organic species is less than 0.1 muM. None of these reactions occurs spontaneously in bulk water. One example demonstrating the possible broad application of reduction in water microdroplets to organic molecules is the reduction of acetophenone to form 1-phenylethanol. Taken together, these results show that microdroplets provide a new foundation for green chemistry by rendering water molecules to be highly electrochemically active without any added reducing agent or applied potential. In this manner, aqueous microdroplets might have provided a route for abiotic reduction reactions in the prebiotic era, thereby providing organic molecules with a reducing power before the advent of biotic reducing machineries.
View details for DOI 10.1021/jacs.9b03227
View details for PubMedID 31244167
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HD (v=1, j=2, m) orientation controls HD-He rotationally inelastic scattering near 1 K
JOURNAL OF CHEMICAL PHYSICS
2019; 150 (17)
View details for DOI 10.1063/1.5096531
View details for Web of Science ID 000467255500025
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Selective Synthesis in Microdroplets of 2-Phenyl-2,3-dihydrophthalazine-1,4-dione from Phenyl Hydrazine with Phthalic Anhydride or Phthalic Acid
CHEMISTRY-A EUROPEAN JOURNAL
2019; 25 (6): 1466-1471
View details for DOI 10.1002/chem.201805585
View details for Web of Science ID 000457477100014
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Mechanistic Study of Ruthenium-Catalyzed C-H Hydroxylation Reveals an Unexpected Pathway for Catalyst Arrest
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2019; 141 (2): 972–80
View details for DOI 10.1021/jacs.8b10950
View details for Web of Science ID 000456350300037
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Mechanistic Study of Ruthenium-Catalyzed C-H Hydroxylation Reveals an Unexpected Pathway for Catalyst Arrest.
Journal of the American Chemical Society
2019
Abstract
We have recently disclosed [(dtbpy)2RuCl2] as an effective precatalyst for chemoselective C-H hydroxylation of C(sp3)-H bonds and have noted a marked disparity in reaction performance between 4,4'-di- tert-butyl-2,2'-bipyridine (dtbpy)- and 2,2'-bipyridine (bpy)-derived complexes. A desire to understand the origin of this difference and to further advance this catalytic method has motivated the comprehensive mechanistic investigation described herein. Details of this reaction have been unveiled through evaluation of ligand structure-activity relationships, electrochemical and kinetic studies, and pressurized sample infusion high-resolution mass spectrometry (PSI-MS). Salient findings from this investigation include the identification of more than one active oxidant and three disparate mechanisms for catalyst decomposition/arrest. Catalyst efficiency, as measured by turnover number, has a strong inverse correlation with the rate and extent of ligand dissociation, which is dependent on the identity of bipyridyl 4,4'-substituent groups. Dissociated bipyridyl ligand is oxidized to mono- and bis- N-oxide species under the reaction conditions, the former of which is found to act as a potent catalyst poison, yielding a catalytically inactive tris-ligated [Ru(dtbpy)2(dtbpy N-oxide)]2+ complex. Insights gained through this work highlight the power of PSI-MS for studies of complex reaction processes and are guiding ongoing efforts to develop high-performance, next-generation catalyst systems for C-H hydroxylation.
View details for PubMedID 30601662
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1,4-Benzoquinone antimicrobial agents against Staphylococcus aureus and Mycobacterium tuberculosis derived from scorpion venom.
Proceedings of the National Academy of Sciences of the United States of America
2019
Abstract
Two 1,4-benzoquinone derivatives, found in the venom of the scorpion Diplocentrus melici following exposure to air, have been isolated, characterized, synthesized, and assessed for antimicrobial activities. Initially a white, viscous liquid, the extracted venom colors within minutes under ambient conditions. From this colored mixture, two compounds, one red, the other blue, were isolated and purified using chromatography. After a variety of NMR and mass spectrometry experiments, the red compound was determined to be 3,5- dimethoxy-2-(methylthio)cyclohexa-2,5-diene-1,4-dione, and the blue compound was determined to be 5-methoxy-2,3- bis(methylthio)cyclohexa-2,5-diene-1,4-dione. Because extremely small amounts of these compounds were isolated from the scorpion venom, we developed laboratory syntheses from commercially available precursors, allowing us to produce sufficient quantities for crystallization and biological assays. The red benzoquinone is effective against Staphylococcus aureus [minimum inhibitory concentration (MIC) = 4 µg/mL], while the blue benzoquinone is active against Mycobacterium tuberculosis (MIC = 4 µg/mL) and even against a multidrug-resistant (MDR) strain with nearly equal effectiveness. The bactericidal effects of both benzoquinones show comparable activity to commercially available antibiotics used against these pathogens and were cytotoxic to neoplastic cell lines, suggesting their potential as lead compounds for the development of novel antimicrobial and anticancer drugs. Importantly, the blue benzoquinone was also effective in vivo with mouse models of MDR tuberculosis infection. After treatment for 2 mo, four mice with late-stage active MDR tuberculosis had a significant decrease in pulmonary bacillary loads and tissue damage. Healthy mice served as negative controls and tolerated treatment well, without adverse side effects.
View details for DOI 10.1073/pnas.1812334116
View details for PubMedID 31182590
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Aqueous Microdroplets Containing Only Ketones or Aldehydes Undergo Dakin and Baeyer-Villiger Reactions
Chemical Science
2019; 10 (48): 10974-10978
View details for DOI 10.1039/C9SC05112K
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Absolute Quantitation of Oxidizable Peptides by Coulometric Mass Spectrometry.
Journal of the American Society for Mass Spectrometry
2019
Abstract
Quantitation methods for peptides using mass spectrometry have advanced rapidly. These methods rely on using standard and/or isotope-labeled peptides, which might be difficult or expensive to synthesize. To tackle this challenge, we present a new approach for absolute quantitation without the use of standards or calibration curves based on coulometry combined with mass spectrometry (MS). In this approach, which we call coulometric mass spectrometry (CMS), the mass spectrum of a target peptide containing one or more tyrosine residues is recorded before and after undergoing electrochemical oxidation. We record the total integrated oxidation current from the electrochemical measurement, which according to the Faraday's Law of coulometry, provides the number of moles of oxidized peptide. The ion intensity ratio of the target peptide before and after oxidation provides an excellent estimate of the fraction of the peptide that has been oxidized, from which the total amount of peptide is calculated. The striking strength of CMS is that it needs no standard peptide, but CMS does require the peptide to contain a known number of oxidizable groups. To illustrate the power of this method, we analyzed various tyrosine-containing peptides such as GGYR, DRVY, oxytocin, [Arg8]-vasotocin and angiotensinogen 1-14 with a quantification error ranging from - 7.5 to + 2.4%. This approach is also applicable to quantifying phosphopeptides and could be useful in proteomics research.
View details for DOI 10.1007/s13361-019-02299-z
View details for PubMedID 31429055
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Influence of Inlet Capillary Temperature on the Microdroplet Chemistry Studied by Mass Spectrometry.
The journal of physical chemistry. A
2019
Abstract
Often, studies of microdroplet chemistry using electrospray ionization mass spectrometry (MS) either find a negligible effect of the heated inlet capillary of the mass spectrometer on the reaction rate or do not consider its effect. In this context, we studied two reactions in microdroplets, the Pomeranz-Fritsch synthesis of isoquinoline and the Combes quinoline synthesis. The reagents were electrosprayed with methanol and aqueous solutions forming small and large microdroplets at flow rates of 1 and 20 μL/min, respectively. We also varied the inlet capillary temperature from 100 to 350 °C. Contrary to the view that the inlet temperature has little to no influence on the reaction rate, we found that the Pomeranz-Fritsch reaction was markedly accelerated for both solvents and for both droplet sizes on increasing the temperature, whereas the Combes synthesis showed the opposite behavior. We propose that these strikingly different behaviors result from a competition of two effects, the evaporative cooling versus the heating of ejected bare ions from the droplet, both taking place inside the heated inlet. This finding suggests that these phenomena must be taken into account while interpreting the microdroplet reactions studied by electrospray or a similar kind of ambient ionization MS.
View details for DOI 10.1021/acs.jpca.9b05703
View details for PubMedID 31433185
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Chemoselective N-alkylation of Indoles in Aqueous Microdroplets.
Angewandte Chemie (International ed. in English)
2019
Abstract
Many reactions show much faster kinetics in microdroplets than that in the bulk phase. Most reported reactions in microdroplets mirror the products found in bulk reactions. However, the unique environment of microdroplets allows different chemistry to occur. In this work, we present the first example of chemoselective N -alkylation of indoles in aqueous microdroplets via a three-component Mannich-type reaction without using any catalyst. In sharp contrast, bulk reactions using the same reagents with a catalyst yield exclusively C-alkylation products. The N -alkylation yield is moderate in microdroplets, up to 53%. We extended the scope of microdroplet reactions and obtained a series of new functionalized indole aminals, likely to have biological activity. This work clearly indicates that microdroplet reactions can show reactivity quite different from bulk phase reactions, which holds great potential for developing novel reactivities in microdroplets.
View details for DOI 10.1002/anie.201913069
View details for PubMedID 31837281
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Stark-induced adiabatic Raman passage examined through the preparation of D2 (v = 2, j = 0) and D2 (v = 2, j = 2, m = 0).
The Journal of chemical physics
2019; 150 (23): 234201
Abstract
We study the conditions that must be met for successful preparation of a large ensemble in a specific target quantum state using Stark-induced adiabatic Raman passage (SARP). In particular, we show that the threshold condition depends on the relative magnitudes of the Raman polarizability (r0v) and the difference of the optical polarizabilities (Δα00→vj) of the initial (v = 0, j = 0) and the target (v, j) rovibrational levels. Here, v and j are the vibrational and rotational quantum numbers, respectively. To illustrate how the operation of SARP is controlled by these two parameters, we experimentally prepared D2 (v = 2, j = 0) and D2 (v = 2, j = 2, m = 0) in a beam of D2 (v = 0, j = 0) molecules using a sequence of partially overlapping pump and Stokes laser pulses. By comparing theory and experiment, we were able to determine the Raman polarizability r02 ≈ 0.3 × 10-41 Cm/(V/m) and the difference polarizabilities Δα00→20 ≈ 1.4 × 10-41 Cm/(V/m) and Δα00→22 ≈ 3.4 × 10-41 Cm/(V/m) for the two Raman transitions. Our experimental data and theoretical calculations show that because the ratio r/Δα is larger for the (0,0) → (2,0) transition than the (0,0) → (2,2) transition, much less optical power is required to transfer a large population to the (v = 2, j = 0) level. Nonetheless, our experiment demonstrates that substantial population transfer to both the D2 (v = 2, j = 0) and D2 (v = 2, j = 2, m = 0) is achieved using appropriate laser fluences. Our derived threshold condition demonstrates that with increasing vibrational quantum number, it becomes more difficult to achieve large amounts of population transfer.
View details for DOI 10.1063/1.5109261
View details for PubMedID 31228886
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HD (v = 1, j = 2, m) orientation controls HD-He rotationally inelastic scattering near 1 K.
The Journal of chemical physics
2019; 150 (17): 174301
Abstract
To investigate how molecular orientations affect low energy scattering, we have studied the rotational relaxation of HD (v = 1, j = 2, m) → (v' = 1, j' = 0) by collision with ground-state He, where v, j, and m designate the vibrational, rotational, and magnetic quantum numbers, respectively. We experimentally probed different collision geometries by preparing three specific m sublevels, including an m entangled sublevel, belonging to a single rovibrational (v = 1, j = 2) energy level within the ground electronic state of HD using Stark-induced adiabatic Raman passage. Low collision energies (0-5 K) were achieved by coexpanding a 1:19 HD:He mixture in a highly collimated supersonic beam, which has defined the direction of the collision velocity and restricted the incoming orbital angular momentum states, defined by the quantum number l, to l ≤ 2. Partial wave analysis of experimental data shows that a single l = 2 input orbital dominates the scattered angular distribution, implying the presence of a collisional resonance. The differential scattering angular distribution exhibits a greater than fourfold stereodynamic preference for the m = 0 input state vs m = ±2, when the quantization axis is oriented parallel to the collision velocity.
View details for PubMedID 31067864
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Absolute Quantitation of Oxidizable Peptides by Coulometric Mass Spectrometry.
Journal of the American Society for Mass Spectrometry
2019; 30 (11): 2398–2407
Abstract
Quantitation methods for peptides using mass spectrometry have advanced rapidly. These methods rely on using standard and/or isotope-labeled peptides, which might be difficult or expensive to synthesize. To tackle this challenge, we present a new approach for absolute quantitation without the use of standards or calibration curves based on coulometry combined with mass spectrometry (MS). In this approach, which we call coulometric mass spectrometry (CMS), the mass spectrum of a target peptide containing one or more tyrosine residues is recorded before and after undergoing electrochemical oxidation. We record the total integrated oxidation current from the electrochemical measurement, which according to the Faraday's Law of coulometry, provides the number of moles of oxidized peptide. The ion intensity ratio of the target peptide before and after oxidation provides an excellent estimate of the fraction of the peptide that has been oxidized, from which the total amount of peptide is calculated. The striking strength of CMS is that it needs no standard peptide, but CMS does require the peptide to contain a known number of oxidizable groups. To illustrate the power of this method, we analyzed various tyrosine-containing peptides such as GGYR, DRVY, oxytocin, [Arg8]-vasotocin and angiotensinogen 1-14 with a quantification error ranging from - 7.5 to + 2.4%. This approach is also applicable to quantifying phosphopeptides and could be useful in proteomics research.
View details for PubMedID 31944744
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Photon catalysis of deuterium iodide photodissociation.
Physical chemistry chemical physics : PCCP
2018
Abstract
A catalyst enhances a reaction pathway without itself being consumed or changed. Recently, there has been growing interest in the concept of "photon catalysis" in which nonresonant photons, which are neither absorbed nor scattered, promote reactions. The driving force behind this effect is the interaction between the strong electric field associated with a pulsed, focused laser and the polarizability of the reacting system. In this study, the effect of near-infrared, nonresonant radiation on the photodissociation of deuterium iodide is demonstrated. We use nanosecond pulses rather than time-resolved spectroscopy to investigate the average effect of the electric field on the branching ratio for forming D + I(2P3/2) and D + I(2P1/2). Changes in the measured D-atom speeds between field-free and strong-field conditions confirm substantial differences in dissociation dynamics. Both the magnitude and direction of change in the branching ratios are dependent upon the photodissociation wavelength. Experiments and theoretical calculations confirm that the mechanism for photon catalysis under these conditions is dynamic Stark shifting of potential energy surfaces rather than electric-field-induced alignment of reagent molecules.
View details for PubMedID 30516765
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Selective synthesis in microdroplets of 2-phenyl-2,3-dihydrophthalazine-1,4-dione from phenyl hydrazine with phthalic anhydride or phthalic acid.
Chemistry (Weinheim an der Bergstrasse, Germany)
2018
Abstract
Pyridazine derivatives are privileged structures because of their potential biological and optical properties. Traditional synthesis methods usually require acid or base as a catalyst under reflux conditions with reaction times ranging from hours to a few days or require microwave assistance to induce the reaction. Herein, we present the accelerated synthesis of a pyridazine derivative, 2-phenyl-2,3-dihydrophthalazine-1,4-dione, PDHP, in electrosprayed microdroplets containing 1:1 v/v mixture of phenyl hydrazine and phthalic anhydride or phthalic acid. This reaction occurred on the submillisecond timescale with good yield (over 90% with the choice of solvent) without using an external catalyst at room temperature. In sharp contrast to the bulk reaction of obtaining a mixture of two products, the reaction in confined microdroplets yield only the important six-membered heterocyclic product PDHP. Results indicated that surface reactions in microdroplets with low pH values cause selectivity, acceleration, and high yield.
View details for PubMedID 30417449
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Supersonic beams of mixed gases: A method for studying cold collisions
CHEMICAL PHYSICS
2018; 514: 150–53
View details for DOI 10.1016/j.chemphys.2018.02.017
View details for Web of Science ID 000448668600017
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Combining Desorption Electrospray Ionization Mass Spectrometry Imaging and Machine Learning for Molecular Recognition of Myocardial Infarction
ANALYTICAL CHEMISTRY
2018; 90 (20): 12198-12206
View details for DOI 10.1021/acs.analchem.8b03410
View details for Web of Science ID 000447816400064
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Combining Desorption Electrospray Ionization Mass Spectrometry Imaging and Machine Learning for Molecular Recognition of Myocardial Infarction.
Analytical chemistry
2018
Abstract
Lipid profile changes in heart muscle have been previously linked to cardiac ischemia and myocardial infarction, but the spatial distribution of lipids and metabolites in ischemic heart remains to be fully investigated. We performed desorption electrospray ionization mass spectrometry imaging of hearts from in vivo myocardial infarction mouse models. In these mice, myocardial ischemia was induced by blood supply restriction via a permanent ligation of left anterior descending coronary artery. We showed that applying the machine learning algorithm of gradient boosting tree ensemble to the ambient mass spectrometry imaging data allows us to distinguish segments of infarcted myocardium from normally perfused hearts on a pixel by pixel basis. The machine learning algorithm selected 62 molecular ion peaks important for classification of each 200 mum-diameter pixel of the cardiac tissue map as normally perfused or ischemic. This approach achieved very high average accuracy (97.4%), recall (95.8%), and precision (96.8%) at a spatial resolution of 200 mum. In addition, we determined the chemical identity of 27 species, mostly small metabolites and lipids, selected by the algorithm as the most significant for cardiac pathology classification. This molecular signature of myocardial infarction may provide new mechanistic insights into cardiac ischemia, assist with infarct size assessment, and point toward novel therapeutic interventions.
View details for PubMedID 30188683
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Real-time mass-spectrometric screening of droplet-scale electrochemical reactions
ANALYST
2018; 143 (18): 4247–50
Abstract
A droplet-scale, real-time electrochemical reaction screening platform based on droplet spray ionization mass spectrometry (DSI-MS) has been developed. The N,N-dimethylaniline (DMA) radical cation with a half-life of microseconds was readily detected by MS during the electrooxidation of DMA, and the subsequent reactions were followed in real time for minutes.
View details for DOI 10.1039/c8an00957k
View details for Web of Science ID 000444553400003
View details for PubMedID 30027961
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Reducing-agent-free and template-free synthesis of metal nanostructures in aqueous microdroplets
AMER CHEMICAL SOC. 2018
View details for Web of Science ID 000447609101400
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Water microdroplets catalyze chemical reactions
AMER CHEMICAL SOC. 2018
View details for Web of Science ID 000447600002433
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Adventures in cold chemistry
AMER CHEMICAL SOC. 2018
View details for Web of Science ID 000447609103482
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An Alkaloid from Scorpion Venom: Chemical Structure and Synthesis
JOURNAL OF NATURAL PRODUCTS
2018; 81 (8): 1899–1904
View details for DOI 10.1021/acs.jnatprod.8b00527
View details for Web of Science ID 000443103700025
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An Alkaloid from Scorpion Venom: Chemical Structure and Synthesis.
Journal of natural products
2018
Abstract
While most scorpion venom components identified in the past are peptidic or proteinic in nature, we report here a new alkaloid isolated from the venom of the Mexican scorpion Megacormus gertschi. Nuclear magnetic resonance and mass spectrometric investigations elucidate the structure of the alkaloid as ( Z)- N-(2-(1 H-imidazol-4-yl)ethyl)-3-(4-hydroxy-3-methoxyphenyl)-2-methoxyacrylamide (1). A chemical method of synthesizing this alkaloid is also described. Although abundant in venom, the above alkaloid was not found to have insecticidal activity. Structural analysis suggests that this venom alkaloid might be of potential interest for evaluating its medicinal effect.
View details for PubMedID 30028606
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Enhancement of reaction rate in small-sized droplets: A combined analytical and simulation study.
The Journal of chemical physics
2018; 148 (24): 244704
Abstract
Several recent mass spectrometry experiments reveal a marked enhancement of the reaction rate of organic reactions in microdroplets. This enhancement has been tentatively attributed to the accumulation of excess charge on a surface, which in turn can give rise to a lowering of activation energy of the reaction. Here we model the reactions in droplets as a three-step process: (i) diffusion of a reactant from the core of the droplet to the surface, (ii) search by diffusion of the reactant on the surface to find a reactive partner, and finally (iii) the intrinsic reaction leading to bond breaking and product formation. We obtain analytic expressions for the mean search time (MST) to find a target located on the surface by a reactant in both two- and three-dimensional droplets. Analytical results show quantitative agreement with Brownian dynamics simulations. We find, as also reported earlier, that the MST varies as R2/D, where R is the radius of the droplet and D is the diffusion constant of the molecules in the droplet medium. We also find that a hydronium ion in the vicinity can substantially weaken the bond and hence lowers the activation barrier. We observe a similar facilitation of bond breaking in the presence of a static dipolar electric field along any of the three Cartesian axes. If the intrinsic reaction is faster compared to the mean search time involved, it becomes primarily a diffusion-controlled process; otherwise the reaction cannot be accelerated in the droplet medium. The air-droplet interface provides a different environment compared to the interior of the droplet. Hence, we might also expect a completely different mechanism and products in the case of droplet reactions.
View details for PubMedID 29960367
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Enhancement of reaction rate in small-sized droplets: A combined analytical and simulation study
JOURNAL OF CHEMICAL PHYSICS
2018; 148 (24)
View details for DOI 10.1063/1.5030114
View details for Web of Science ID 000437190300077
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Preparative microdroplet synthesis of carboxylic acids from aerobic oxidation of aldehydes
CHEMICAL SCIENCE
2018; 9 (23): 5207–11
View details for DOI 10.1039/c8sc01580e
View details for Web of Science ID 000435350200011
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Preparative microdroplet synthesis of carboxylic acids from aerobic oxidation of aldehydes.
Chemical science
2018; 9 (23): 5207-5211
Abstract
Single liquid-phase and liquid-liquid phase reactions in microdroplets have shown much faster kinetics than that in the bulk phase. This work extends the scope of microdroplet reactions to gas-liquid reactions and achieves preparative synthesis. We report highly efficient aerobic oxidation of aldehydes to carboxylic acids in microdroplets. Molecular oxygen plays two roles: (1) as the sheath gas to shear the aldehyde solution into microdroplets, and (2) as the sole oxidant. The dramatic increase of the surface-area-to-volume ratio of microdroplets compared to bulk solution, and the efficient mixing of gas and liquid phases using spray nozzles allow effective mass transfer between aldehydes and molecular oxygen. The addition of catalytic nickel(ii) acetate is shown to accelerate further microdroplet reactions of this kind. We show that aliphatic, aromatic, and heterocyclic aldehydes can be oxidized to the corresponding carboxylic acids in a mixture of water and ethanol using the nickel(ii) acetate catalyst, in moderate to excellent yields (62-91%). The microdroplet synthesis is scaled up to make it preparative. For example, aerobic oxidation of 4-tert-butylbenzaldehyde to 4-tert-butylbenzoic acid was achieved at a rate of 10.5 mg min-1 with an isolated product yield of 66%.
View details for DOI 10.1039/c8sc01580e
View details for PubMedID 29997875
View details for PubMedCentralID PMC6001248
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In Situ Mass Spectrometric Screening and Studying of the Fleeting Chain Propagation of Aniline
ANALYTICAL CHEMISTRY
2018; 90 (12): 7154–57
Abstract
A simple and effective approach to studying the mechanism of electrooxidation of aniline (ANI) is reported in this paper. It was accomplished by an innovative electrochemistry (EC)-mass spectrometry (MS) coupling, which can sample directly from a droplet-scale reacting electrolyte for mass spectrometric analysis. With this setup, the polymer chain growth of ANI could be monitored in situ and in real-time. The short-lived radical cations (ANI•+, m/ z 93.06) as well as the soluble dimer ( m/ z 183.09) and oligomers ( m/ z 274.13, 365.18, ...) were successfully captured. Using the EC-MS and tandem mass spectrometry, the dimers produced by head-to-tail (4-aminodiphenylamine), head-to-head (hydrazobenzene), and tail-to-tail (benzidine) coupling of radical cations were found in the same polymerization process. Moreover, the EC-MS method was also applicable for determining the propagation speed of ANI when applying different electrolyte salts and oxidizing potentials.
View details for PubMedID 29873225
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Distinguishing malignant from benign microscopic skin lesions using desorption electrospray ionization mass spectrometry imaging
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2018; 115 (25): 6347–52
View details for DOI 10.1073/pnas.1803733115
View details for Web of Science ID 000435585200035
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Electrically controlled drug release using pH-sensitive polymer films
NANOSCALE
2018; 10 (21): 10087-10093
View details for DOI 10.1039/c8nr02602e
View details for Web of Science ID 000434313200031
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Fluorescence Polarization Anisotropy in Microdroplets
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
2018; 9 (11): 2928-2932
View details for DOI 10.1021/acs.jpclett.8b01129
View details for Web of Science ID 000435026100034
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Surface characterization and free thyroid hormones response of chemically modified poly(ethylene terephthalate) blood collection tubes
APPLIED SURFACE SCIENCE
2018; 442: 602–12
View details for DOI 10.1016/j.apsusc.2018.02.177
View details for Web of Science ID 000428294500070
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Electrically controlled drug release using pH-sensitive polymer films.
Nanoscale
2018; 10 (21): 10087–93
Abstract
Drug delivery systems (DDS) that allow spatially and temporally controlled release of drugs are of particular interest in the field of drug delivery. These systems create opportunities for individually tailored doses of drugs to be administered as well as reduce side effects by localizing the initial drug dose to the organ of interest. We present an electroresponsive DDS in the form of a bioresorbable nanocomposite film which operates at low voltages (<-2 V). The method is based on electrochemically generating local pH changes at an electrode surface to induce dissolution of a pH-sensitive polymer, which is used as the carrier material. We previously demonstrated this proof-of-concept using a poly(methyl methacrylate-co-methacrylic acid) (co-PMMA) copolymer commercially marketed as Eudragit S100 (EGT). However, as EGT is soluble at a pH above 7, experiments were performed in isotonic saline solutions (pH 6.4). In this work, we have synthesized co-PMMA with a variety of monomer ratios to shift the solubility of the copolymer to higher pH values, and developed a polymer that can be used under physiologically relevant conditions. The generalizability of this system was demonstrated by showing controlled release of different drug molecules with varying parameters like size, hydrophobicity, and pKa. Fluorescein, a hydrophilic model compound, meloxicam, a hydrophobic anti-arthritic medication, curcumin, a small molecule with anti-cancer therapeutic potential, and insulin, a polypeptide hormone used in the treatment of hypoglycemia, could all be released on demand with minimal leakage. The drug loading achieved was 32 wt% by weight of the co-polymer.
View details for PubMedID 29781009
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Ultra-low voltage triggered release of an anticancer drug from polypyrrole nanoparticles
NANOSCALE
2018; 10 (20): 9773–79
Abstract
We have synthesized polypyrrole nanoparticles using three different oxidizing agents (hydrogen peroxide, chloroauric acid and ferric chloride) and shown that films assembled from these nanoparticles have significantly different drug release profiles. When ferric chloride is used as the oxidizing agent, it is possible to release drugs at voltages as low as -0.05 V, almost an order of magnitude lower than typically used voltages. These ultra-low voltage responsive nanoparticles widen the window of operation of conducting polymers and enable delivery of redox active drugs. As an example, we have shown pulsed release of the chemotherapeutic methotrexate at voltages as low as -0.075 V, demonstrating the potential application of these nanoparticles in cancer treatment. We have also verified the anti-tumor efficacy of the released drug using PC12 cell cultures.
View details for PubMedID 29767192
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Fluorescence Polarization Anisotropy in Microdroplets.
The journal of physical chemistry letters
2018: 2928–32
Abstract
Chemical reactions can be greatly accelerated in microdroplets, but the factors that lead to acceleration are still being elucidated. Using rhodamine 6G (R6G) as a model compound, we studied the density distribution and fluorescence polarization anisotropy of this dye in water-in-oil microdroplets. We found the density of R6G is higher on the surface of the microdroplets, and the ratio of the surface density to that of the center grows with increasing microdroplet radius or with decreasing R6G concentration. The measured fluorescence polarization anisotropy at the surface is almost the same for droplets of different sizes but becomes larger when the concentration is lowered. We also performed three-dimensional simulations by treating R6G+ and its associated anion as a dipole of fixed length and magnitude. The simulation results match quite well the experimental measurements, showing that the density distribution and fluorescence polarization anisotropy can be largely explained by a simple electrostatic model.
View details for PubMedID 29763551
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Mechanistic Analysis of the C-H Amination Reaction of Menthol by CuBr2 and Selectfluor
JOURNAL OF ORGANIC CHEMISTRY
2018; 83 (10): 5681–87
Abstract
The mechanism of the Ritter-type C-H amination reaction of menthol with acetonitrile using CuBr2, Selectfluor, and Zn(OTf)2, first disclosed by Baran and coworkers in 2012, was studied using a combination of online electrospray ionization mass spectrometry, continuous UV/vis spectrometric monitoring, and density functional theory calculations. In addition to corroborating Baran's original mechanistic proposal, these studies uncovered a second pathway to product formation, which likely only occurs in microdroplets. DFT calculations show that neither pathway has a barrier that is greater than 6.8 kcal/mol, suggesting that both mechanisms are potentially operative under ambient conditions.
View details for PubMedID 29683651
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Nanomaterial Preparation by Extrusion through Nanoporous Membranes
SMALL
2018; 14 (18): e1703493
Abstract
Template synthesis represents an important class of nanofabrication methods. Herein, recent advances in nanomaterial preparation by extrusion through nanoporous membranes that preserve the template membrane without sacrificing it, which is termed as "non-sacrificing template synthesis," are reviewed. First, the types of nanoporous membranes used in nanoporous membrane extrusion applications are introduced. Next, four common nanoporous membrane extrusion strategies: vesicle extrusion, membrane emulsification, precipitation extrusion, and biological membrane extrusion, are examined. These methods have been utilized to prepare a wide range of nanomaterials, including liposomes, emulsions, nanoparticles, nanofibers, and nanotubes. The principle and historical context of each specific technology are discussed, presenting prominent examples and evaluating their positive and negative features. Finally, the current challenges and future opportunities of nanoporous membrane extrusion methods are discussed.
View details for PubMedID 29468837
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Cold quantum-controlled rotationally inelastic scattering of HD with H-2 and D-2 reveals collisional partner reorientation
NATURE CHEMISTRY
2018; 10 (5): 561–67
Abstract
Molecular interactions are best probed by scattering experiments. Interpretation of these studies has been limited by lack of control over the quantum states of the incoming collision partners. We report here the rotationally inelastic collisions of quantum-state prepared deuterium hydride (HD) with H2 and D2 using a method that provides an improved control over the input states. HD was coexpanded with its partner in a single supersonic beam, which reduced the collision temperature to 0-5 K, and thereby restricted the involved incoming partial waves to s and p. By preparing HD with its bond axis preferentially aligned parallel and perpendicular to the relative velocity of the colliding partners, we observed that the rotational relaxation of HD depends strongly on the initial bond-axis orientation. We developed a partial-wave analysis that conclusively demonstrates that the scattering mechanism involves the exchange of internal angular momentum between the colliding partners. The striking differences between H2/HD and D2/HD scattering suggest the presence of anisotropically sensitive resonances.
View details for PubMedID 29662208
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Microdroplets Accelerate Ring Opening of Epoxides
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
2018; 29 (5): 1036–43
Abstract
The nucleophilic opening of an epoxide is a classic organic reaction that has widespread utility in both academic and industrial applications. We have studied the reaction of limonene oxide with morpholine to form 1-methyl-2-morpholino-4-(prop-1-en-2-yl) cyclohexan-1-ol in bulk solution and in electrosprayed microdroplets with a 1:1 v/v water/methanol solvent system. We find that even after 90 min at room temperature, there is no product detected by nuclear magnetic resonance spectroscopy in bulk solution whereas in room-temperature microdroplets (2-3 μm in diameter), the yield is already 0.5% in a flight time of 1 ms as observed by mass spectrometry. This constitutes a rate acceleration of ~ 105 in the microdroplet environment, if we assume that as much as 5% of product is formed in bulk after 90 min of reaction time. We examine how the reaction rate depends on droplet size, solvent composition, sheath gas pressure, and applied voltage. These factors profoundly influence the extent of reaction. This dramatic acceleration is not limited to just one system. We have also found that the nucleophilic opening of cis-stilbene oxide by morpholine is similarly accelerated. Such large acceleration factors in reaction rates suggest the use of microdroplets for ring opening of epoxides in other systems, which may have practical significance if such a procedure could be scaled. Graphical Abstract This graphical image is distorted. It is too extended in the vertical direction. Please fix.ᅟ.
View details for PubMedID 29569167
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Autonomy and accountability in institutions of higher education
CURRENT SCIENCE
2018; 114 (8): 1603–4
View details for Web of Science ID 000430655100008
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Spontaneous formation of gold nanostructures in aqueous microdroplets
NATURE COMMUNICATIONS
2018; 9: 1562
Abstract
The synthesis of gold nanostructures has received widespread attention owing to many important applications. We report the accelerated synthesis of gold nanoparticles (AuNPs), as well as the reducing-agent-free and template-free synthesis of gold nanoparticles and nanowires in aerosol microdroplets. At first, the AuNP synthesis are carried out by fusing two aqueous microdroplet streams containing chloroauric acid and sodium borohydride. The AuNPs (~7 nm in diameter) are produced within 60 µs at the rate of 0.24 nm µs-1. Compared to bulk solution, microdroplets enhance the size and the growth rate of AuNPs by factors of about 2.1 and 1.2 × 105, respectively. Later, we find that gold nanoparticles and nanowires (~7 nm wide and >2000 nm long) are also formed in microdroplets in the absence of any added reducing agent, template, or externally applied charge. Thus, water microdroplets not only accelerate the synthesis of AuNPs by orders of magnitude, but they also cause spontaneous formation of gold nanostructures.
View details for PubMedID 29674623
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Rotationally inelastic scattering of HD (v=1, j=2) with H2 or D2 near 1 Kelvin
AMER CHEMICAL SOC. 2018
View details for Web of Science ID 000435539905444
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Upgrading asphaltenes by oil droplets striking a charged TiO2-immobilized paper surface
AMER CHEMICAL SOC. 2018
View details for Web of Science ID 000435539900411
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Spontaneous Reduction of Biomolecules on the Surface of Water Droplets
CELL PRESS. 2018: 542A
View details for Web of Science ID 000430563200462
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Abiotic Fabrication of Sugar Phosphates and Ribonucleosides in Water Microdroplets
CELL PRESS. 2018: 438A
View details for Web of Science ID 000430450000685
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Quantum interference in chemical reactions
PHYSICS TODAY
2018; 71 (2): 70–71
View details for Web of Science ID 000424052800019
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Site-selective bromination of sp3 C-H bonds.
Chemical science
2018; 9 (1): 100-104
Abstract
A method for converting sp3 C-H to C-Br bonds using an N-methyl sulfamate directing group is described. The reaction employs Rh2(oct)4 and a mixture of NaBr and NaOCl and is performed in aqueous solution open to air. For all sulfamates examined, oxidation occurs with high selectivity at the γ-carbon, affording a uniquely predictable method for C-H bond halogenation. Results from a series of mechanistic experiments suggest that substrate oxidation likely proceeds by a radical chain process. Initial formation of an N-halogenated sulfamate followed by Rh-mediated homolysis generates an N-centered radical, which serves as the active oxidant.
View details for DOI 10.1039/c7sc04611a
View details for PubMedID 29629078
View details for PubMedCentralID PMC5873043
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Abiotic synthesis of purine and pyrimidine ribonucleosides in aqueous microdroplets
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2018; 115 (1): 36–40
Abstract
Aqueous microdroplets (<1.3 µm in diameter on average) containing 15 mM d-ribose, 15 mM phosphoric acid, and 5 mM of a nucleobase (uracil, adenine, cytosine, or hypoxanthine) are electrosprayed from a capillary at +5 kV into a mass spectrometer at room temperature and 1 atm pressure with 3 mM divalent magnesium ion (Mg2+) as a catalyst. Mass spectra show the formation of ribonucleosides that comprise a four-letter alphabet of RNA with a yield of 2.5% of uridine (U), 2.5% of adenosine (A), 0.7% of cytidine (C), and 1.7% of inosine (I) during the flight time of ∼50 µs. In the case of uridine, no catalyst is required. An aqueous solution containing guanine cannot be generated under the same conditions given the extreme insolubility of guanine in water. However, inosine can base pair with cytidine and thus substitute for guanosine. Thus, a full set of ribonucleosides to generate the purine-pyrimidine base pairs A-U and I-C are spontaneously generated in aqueous microdroplets under similar mild conditions.
View details for PubMedID 29255025
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Distinguishing malignant from benign microscopic skin lesions using desorption electrospray ionization mass spectrometry imaging.
Proceedings of the National Academy of Sciences of the United States of America
2018
Abstract
Detection of microscopic skin lesions presents a considerable challenge in diagnosing early-stage malignancies as well as in residual tumor interrogation after surgical intervention. In this study, we established the capability of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to distinguish between micrometer-sized tumor aggregates of basal cell carcinoma (BCC), a common skin cancer, and normal human skin. We analyzed 86 human specimens collected during Mohs micrographic surgery for BCC to cross-examine spatial distributions of numerous lipids and metabolites in BCC aggregates versus adjacent skin. Statistical analysis using the least absolute shrinkage and selection operation (Lasso) was employed to categorize each 200-µm-diameter picture element (pixel) of investigated skin tissue map as BCC or normal. Lasso identified 24 molecular ion signals, which are significant for pixel classification. These ion signals included lipids observed at m/z 200-1,200 and Krebs cycle metabolites observed at m/z < 200. Based on these features, Lasso yielded an overall 94.1% diagnostic accuracy pixel by pixel of the skin map compared with histopathological evaluation. We suggest that DESI-MSI/Lasso analysis can be employed as a complementary technique for delineation of microscopic skin tumors.
View details for PubMedID 29866838
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Pathogen-Imprinted Organosiloxane Polymers as Selective Biosensors for the Detection of Targeted E. coli.
C
2018; 4 (2): 29
Abstract
Early detection of pathogens requires methods that are fast, selective, sensitive and affordable. We report the development of a biosensor with high sensitivity and selectivity based on the low-cost preparation of organosiloxane (OSX) polymers imprinted with E. coli-GFP (green fluorescent protein). OSX polymers with high optical transparency, no cracking, and no shrinkage were prepared by varying several parameters of the sol-gel reaction. The unique shape and chemical fingerprint of the targeted inactivated E. coli-GFP were imprinted into bulk polymers by replication imprinting where the polymer solution was dropcast onto a bacteria template that produced a replica of the bacterial shape and chemistry on the polymer surface upon removal of the template. Capture performances were studied under non-laminar flow conditions with samples containing inactivated E. coli-GFP and compared to inactivated S. typhimurium-GFP. Capture selectivity ratios are dependent on the type of alkoxysilanes used, the H2O:silane molar ratio, and the polymerization temperature. The bacteria concentration in suspension ranged from ~6 × 105 to 1.6 × 109 cells/mL. E. coli-imprinted OSX polymers with polyethylene glycol (PEG) differentiated between the targeted bacterium E. coli, and non-targeted bacteria S. typhimurium and native E. coli-GFP, achieving selectivity ratios up to 4.5 times higher than polydimethylsiloxane (PDMS) and OSX polymers without PEG.
View details for DOI 10.3390/c4020029
View details for PubMedID 33381537
View details for PubMedCentralID PMC7743956
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Nonresonant photons catalyze photodissociation of phenol.
Journal of the American Chemical Society
2018
Abstract
Phenol represents an ideal polyatomic system for demonstrating photon catalysis because of its large polarizability, well-characterized excited-state potential energy surfaces, and nonadiabatic dissociation dynamics. A nonresonant IR pulse (1064 nm) supplies a strong electric field (εo = 4 x 107 V/cm) during the photolysis of isolated phenol (C6H5OH) molecules to yield C6H5O + H near two known energetic thresholds: the S1/S2 conical intersection and the S1 - S0 origin. H-atom speed distributions show marked changes in the relative contributions of dissociative pathways in both cases, compared to the absence of the nonresonant IR pulse. Results indicate that nonresonant photons lower the activation barrier for some pathways relative to others by dynamically Stark shifting the excited-state potential energy surfaces rather than aligning molecules in the strong electric field. Theoretical calculations offer support for the experimental interpretation.
View details for PubMedID 30571915
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Site-selective bromination of sp3 C–H bonds
Chem.Sci
2018; 9: 100-104
Abstract
A method for converting sp3 C-H to C-Br bonds using an N-methyl sulfamate directing group is described. The reaction employs Rh2(oct)4 and a mixture of NaBr and NaOCl and is performed in aqueous solution open to air. For all sulfamates examined, oxidation occurs with high selectivity at the γ-carbon, affording a uniquely predictable method for C-H bond halogenation. Results from a series of mechanistic experiments suggest that substrate oxidation likely proceeds by a radical chain process. Initial formation of an N-halogenated sulfamate followed by Rh-mediated homolysis generates an N-centered radical, which serves as the active oxidant.
View details for DOI 10.1039/C7SC04611A
View details for PubMedCentralID PMC5873043
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Optimizing Chemical Reactions with Deep Reinforcement Learning
ACS CENTRAL SCIENCE
2017; 3 (12): 1337–44
Abstract
Deep reinforcement learning was employed to optimize chemical reactions. Our model iteratively records the results of a chemical reaction and chooses new experimental conditions to improve the reaction outcome. This model outperformed a state-of-the-art blackbox optimization algorithm by using 71% fewer steps on both simulations and real reactions. Furthermore, we introduced an efficient exploration strategy by drawing the reaction conditions from certain probability distributions, which resulted in an improvement on regret from 0.062 to 0.039 compared with a deterministic policy. Combining the efficient exploration policy with accelerated microdroplet reactions, optimal reaction conditions were determined in 30 min for the four reactions considered, and a better understanding of the factors that control microdroplet reactions was reached. Moreover, our model showed a better performance after training on reactions with similar or even dissimilar underlying mechanisms, which demonstrates its learning ability.
View details for PubMedID 29296675
View details for PubMedCentralID PMC5746857
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Formation of Polymeric Nanocubes by Self-Assembly and Crystallization of Dithiolane-Containing Triblock Copolymers
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2017; 56 (51): 16357–62
View details for DOI 10.1002/anie.201709564
View details for Web of Science ID 000419399800041
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"On-Droplet" Chemistry: The Cycloaddition of Diethyl Azodicarboxylate and Quadricyclane
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2017; 56 (47): 15083–87
Abstract
Sharpless and co-workers previously studied the [2σ+2σ+2π] cycloaddition of diethyl azodicarboxylate (DEAD) and quadricyclane and reported that the addition of water to the neat reagents caused an acceleration in the reaction rate, giving birth to what has been called "on-water" chemistry. We have examined the same reaction in aqueous microdroplets (ca. 5 μm diameter) and find that the cycloaddition reaction is accelerated even further (by a factor of 102 ) compared to that of the "on-water" reaction reported previously. The trends of acceleration in solvents other than water demonstrated by Sharpless and colleagues were replicated in the corresponding microdroplet experiments. We also find that DEAD reacts with itself to form a variety of hydrazine carboxylates and intercept intermediates of this reaction in microdroplets to validate a mechanism proposed herein. We suggest that "on-droplet" chemistry, similar to "on-water" chemistry, may be a general process of synthetic interest.
View details for PubMedID 28992393
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On-demand electrically controlled drug release from resorbable nanocomposite films
NANOSCALE
2017; 9 (42): 16429–36
Abstract
Electroresponsive materials are promising carriers for developing drug delivery systems (DDSs) with excellent spatial, temporal, and dosage control over drug release. Current electroresponsive systems use high voltages (2-25 V), are not bioresorbable, or use materials with unknown long-term biocompatibility. We report here a nanocomposite film that is resorbable, electroresponsive at low voltages (<-2 V), and composed of entirely FDA-approved materials. Our DDS is based on poly(methyl methacrylate-co-methacrylic acid), commercially marketed as Eudragit S100 (EGT), which has pH-dependent aqueous solubility. Nanometric films of drug-loaded EGT were designed, synthesized, and coated with a protective layer of chitosan. We hypothesized that electric stimuli would cause local pH changes on the working electrode, leading to pH-responsive dissolution of EGT with concomitant drug release. Our results confirm that local pH changes impart electroresponsive release behavior to the films. Furthermore, drug release scales linearly with voltage, current, and time. The generalizability of the system is shown through the release of several molecules of varying hydrophobicity, pKa, and size, including fluorescein (free acid and sodium salt), curcumin, meloxicam, and glucagon. The ability to modulate drug release with the applied stimulus can be utilized to design minimally invasive drug delivery devices based on bioresorbable electronics. Such devices would allow for personalized medicine in the treatment of chronic diseases.
View details for PubMedID 29058737
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Upgrading Asphaltenes by Oil Droplets Striking a Charged TiO2-Immobilized Paper Surface
ENERGY & FUELS
2017; 31 (11): 12685–90
View details for DOI 10.1021/acs.energyfuels.7b02338
View details for Web of Science ID 000416204800120
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Formation of Polymeric Nanocubes by Self-Assembly and Crystallization of Dithiolane-Containing Triblock Copolymers.
Angewandte Chemie (International ed. in English)
2017
Abstract
Template-free fabrication of non-spherical polymeric nanoparticles is desirable for various applications, but has had limited success owing to thermodynamic favorability of sphere formation. Herein we present a simple way to prepare cubic nanoparticles of block copolymers by self-assembly from aqueous solutions at room temperature. Nanocubes with edges of 40-200 nm are formed spontaneously on different surfaces upon water evaporation from micellar solutions of triblock copolymers containing a central poly(ethylene oxide) block and terminal trimethylene carbonate/dithiolane blocks. These polymers self-assemble into 28±5 nm micelles in water. Upon drying, micelle aggregation and a kinetically controlled crystallization of central blocks evidently induce solid cubic particle formation. An approach for preserving the structures of these cubes in water by thiol- or photo-induced crosslinking was developed. The ability to solubilize a model hydrophobic drug, curcumin, was also explored.
View details for PubMedID 29080292
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Pomeranz-Fritsch Synthesis of Isoquinoline: Gas-Phase Collisional Activation Opens Additional Reaction Pathways
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2017; 139 (41): 14352–55
Abstract
We have investigated the gas-phase production of isoquinoline by performing collisional activation on benzalaminoacetal, the first intermediate in the classic solution-phase Pomeranz-Fritsch synthesis of isoquinoline. We have elucidated the reaction pathways in the gas phase using tandem mass spectrometry. Unlike the corresponding condensed-phase reaction, where catalytic proton exchange between intermediate(s) and solvent (Brønsted-Lowry base) is known to drive the reaction, the gas-phase reaction follows the "mobile proton model" to form the products via a number of intermediates, some the same as in their condensed-phase counterparts. Energy-resolved mass spectrometry, deuterium labeling experiments, and theoretical calculations (B3LYP/6-31G**) identified 27 different reaction routes in the gas phase, forming a complex interlinked reaction network. The experimental measurements and theoretical calculations confirm the proton hopping onto different basic sites of the precursors and intermediates to transform them ultimately into isoquinoline.
View details for DOI 10.1021/jacs.7b06813
View details for Web of Science ID 000413503300006
View details for PubMedID 28949532
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Mechanism of Catalytic Oxidation of Styrenes with Hydrogen Peroxide in the Presence of Cationic Palladium(II) Complexes
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2017; 139 (36): 12495–503
Abstract
Kinetic studies, isotope labeling, and in situ high-resolution mass spectrometry are used to elucidate the mechanism for the catalytic oxidation of styrenes using aqueous hydrogen peroxide (H2O2) and the cationic palladium(II) compound, [(PBO)Pd(NCMe)2][OTf]2 (PBO = 2-(pyridin-2-yl)benzoxazole). Previous studies have shown that this reaction yields acetophenones with high selectivity. We find that H2O2 binds to Pd(II) followed by styrene binding to generate a Pd-alkylperoxide that liberates acetophenone by at least two competitive processes, one of which involves a palladium enolate intermediate that has not been previously observed in olefin oxidation reactions. We suggest that acetophenone is formed from the palladium enolate intermediate by protonation from H2O2. We replaced hydrogen peroxide with t-butyl hydroperoxide and found that, although the palladium enolate intermediate was observed, it was not on the major product-generating pathway, indicating that the form of the oxidant plays a key role in the reaction mechanism.
View details for PubMedID 28849921
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Nanoaggregates of Diverse Asphaltenes by Mass Spectrometry and Molecular Dynamics
ENERGY & FUELS
2017; 31 (9): 9140-9151
View details for DOI 10.1021/acs.energyfuels.7b01420
View details for Web of Science ID 000411771200031
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Metabolic aging by MYC: Distinct lipid accumulation and phospholipid suppression by MYC in lungs and kidneys detected by Desorption Electro Spray Ionization Mass Spectrometry Imaging (DESI-MSI)
PERGAMON-ELSEVIER SCIENCE LTD. 2017: 117
View details for DOI 10.1016/j.exger.2017.02.038
View details for Web of Science ID 000404494300048
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Stark-induced adiabatic Raman ladder for preparing highly vibrationally excited quantum states of molecular hydrogen
JOURNAL OF PHYSICS B-ATOMIC MOLECULAR AND OPTICAL PHYSICS
2017; 50 (14)
View details for DOI 10.1088/1361-6455/aa786f
View details for Web of Science ID 000404466000001
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Introducing mass spectrometry to first-year undergraduates: Analysis of caffeine and other components in energy drinks using paper-spray mass spectrometry
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
2017; 418: 156-161
View details for DOI 10.1016/j.ijms.2016.09.019
View details for Web of Science ID 000405154000022
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Ionic and Neutral Mechanisms for C-H Bond Silylation of Aromatic Heterocycles Catalyzed by Potassium tert-Butoxide.
Journal of the American Chemical Society
2017; 139 (20): 6880-6887
Abstract
Exploiting C-H bond activation is difficult, although some success has been achieved using precious metal catalysts. Recently, it was reported that C-H bonds in aromatic heterocycles were converted to C-Si bonds by reaction with hydrosilanes under the catalytic action of potassium tert-butoxide alone. The use of Earth-abundant potassium cation as a catalyst for C-H bond functionalization seems to be without precedent, and no mechanism for the process was established. Using ambient ionization mass spectrometry, we are able to identify crucial ionic intermediates present during the C-H silylation reaction. We propose a plausible catalytic cycle, which involves a pentacoordinate silicon intermediate consisting of silane reagent, substrate, and the tert-butoxide catalyst. Heterolysis of the Si-H bond, deprotonation of the heteroarene, addition of the heteroarene carbanion to the silyl ether, and dissociation of tert-butoxide from silicon lead to the silylated heteroarene product. The steps of the silylation mechanism may follow either an ionic route involving K(+) and (t)BuO(-) ions or a neutral heterolytic route involving the [KO(t)Bu]4 tetramer. Both mechanisms are consistent with the ionic intermediates detected experimentally. We also present reasons why KO(t)Bu is an active catalyst whereas sodium tert-butoxide and lithium tert-butoxide are not, and we explain the relative reactivities of different (hetero)arenes in the silylation reaction. The unique role of KO(t)Bu is traced, in part, to the stabilization of crucial intermediates through cation-π interactions.
View details for DOI 10.1021/jacs.6b13032
View details for PubMedID 28462580
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Rapid Hydrogen-Deuterium Exchange in Liquid Droplets.
Journal of the American Chemical Society
2017; 139 (20): 6851-6854
Abstract
The rate of hydrogen-deuterium exchange (HDX) in aqueous droplets of phenethylamine has been determined with submillisecond temporal resolution by mass spectrometry using nanoelectrospray ionization with a theta-capillary. The average speed of the microdroplets is measured using microparticle image velocimetry. The droplet travel time is varied from 20 to 320 μs by changing the distance between the emitter and the heated inlet to the mass spectrometer and the voltage applied to the emitter source. The droplets were found to accelerate by ∼30% during their observable travel time. Our droplet imaging shows that the theta-capillary produces two Taylor cone-jets (one per channel), causing mixing to take place from droplet fusion in the Taylor spray zone. Phenethylamine (ϕCH2CH2NH2) was chosen to study because it has only one functional group (-NH2) that undergoes rapid HDX. We model the HDX with a system of ordinary differential equations. The rate constant for the formation of -NH2D(+) from -NH3(+) is 3660 ± 290 s(-1), and the rate constant for the formation of -NHD2(+) from -NH2D(+) is 3330 ± 270 s(-1). The observed rates are about 3 times faster than what has been reported for rapidly exchangeable peptide side-chain groups in bulk measurements using stopped-flow kinetics and NMR spectroscopy. We also applied this technique to determine the HDX rates for a small 10-residue peptide, angiotensin I, in aqueous droplets, from which we found a 7-fold acceleration of HDX in the droplet compared to that in bulk solution.
View details for DOI 10.1021/jacs.7b03541
View details for PubMedID 28481522
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Potassium tert-Butoxide-Catalyzed Dehydrogenative C-H Silylation of Heteroaromatics: A Combined Experimental and Computational Mechanistic Study.
Journal of the American Chemical Society
2017; 139 (20): 6867-6879
Abstract
We recently reported a new method for the direct dehydrogenative C-H silylation of heteroaromatics utilizing Earth-abundant potassium tert-butoxide. Herein we report a systematic experimental and computational mechanistic investigation of this transformation. Our experimental results are consistent with a radical chain mechanism. A trialkylsilyl radical may be initially generated by homolytic cleavage of a weakened Si-H bond of a hypercoordinated silicon species as detected by IR, or by traces of oxygen which can generate a reactive peroxide by reaction with [KOt-Bu]4 as indicated by density functional theory (DFT) calculations. Radical clock and kinetic isotope experiments support a mechanism in which the C-Si bond is formed through silyl radical addition to the heterocycle followed by subsequent β-hydrogen scission. DFT calculations reveal a reasonable energy profile for a radical mechanism and support the experimentally observed regioselectivity. The silylation reaction is shown to be reversible, with an equilibrium favoring products due to the generation of H2 gas. In situ NMR experiments with deuterated substrates show that H2 is formed by a cross-dehydrogenative mechanism. The stereochemical course at the silicon center was investigated utilizing a (2)H-labeled silolane probe; complete scrambling at the silicon center was observed, consistent with a number of possible radical intermediates or hypercoordinate silicates.
View details for DOI 10.1021/jacs.6b13031
View details for PubMedID 28403611
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The obsession with being number one
CURRENT SCIENCE
2017; 112 (9): 1796
View details for Web of Science ID 000401729500001
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Can all bulk-phase reactions be accelerated in microdroplets?
ANALYST
2017; 142 (9): 1399-1402
Abstract
Recent studies have shown that microdroplet reactions are markedly accelerated compared to the corresponding bulk-phase reactions. This raises the question whether all reactions can be sped up by this means. We present a counter example, and we show that the reaction mechanism in microdroplets can differ sharply from that in bulk, especially because of the distinct microdroplet surface environment. This analysis helps to guide us how to choose and control reactions in microdroplets and provides a possible perspective on utilizing microdroplet chemistry to scale up synthesis.
View details for DOI 10.1039/c6an02225a
View details for PubMedID 28332662
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Oncogene KRAS activates fatty acid synthase, resulting in specific ERK and lipid signatures associated with lung adenocarcinoma
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2017; 114 (17): 4300-4305
Abstract
KRAS gene mutation causes lung adenocarcinoma. KRAS activation has been associated with altered glucose and glutamine metabolism. Here, we show that KRAS activates lipogenesis, and this activation results in distinct proteomic and lipid signatures. By gene expression analysis, KRAS is shown to be associated with a lipogenesis gene signature and specific induction of fatty acid synthase (FASN). Through desorption electrospray ionization MS imaging (DESI-MSI), specific changes in lipogenesis and specific lipids are identified. By the nanoimmunoassay (NIA), KRAS is found to activate the protein ERK2, whereas ERK1 activation is found in non-KRAS-associated human lung tumors. The inhibition of FASN by cerulenin, a small molecule antibiotic, blocked cellular proliferation of KRAS-associated lung cancer cells. Hence, KRAS is associated with activation of ERK2, induction of FASN, and promotion of lipogenesis. FASN may be a unique target for KRAS-associated lung adenocarcinoma remediation.
View details for DOI 10.1073/pnas.1617709114
View details for PubMedID 28400509
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Inhibition of MYC-induced lipogenesis prevents renal cell carcinoma initiation and progression
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430568500496
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Preparation of a single highly vibrationally excited quantum state using Stark induced adiabatic Raman passage
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430569106215
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Effect of the application of a non-resonant electric field on the photodissociation dynamics of HBr
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430568502311
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Superfast two-phase reactions in microdroplets without the use of phase transfer catalyst
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430568500497
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Mass spectrometric imaging of prostate biopsy samples: Cancer margin assessment from the distribution of small metabolites and lipids
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430568500539
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Electroresponsive drug delivery using conducting polymer nanoparticles
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430569107388
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Electrospray mass spectrometry using an organosiloxane polymer
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430568500385
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Selective and sensitive capture of pathogens on imprinted Sol-gel polymers
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430568500460
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Monitoring rapid reactions with ambient pressure ionization mass spectrometry
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430568500414
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Personal information from latent fingerprints obtained by mass spectrometry using machine learning
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430568500740
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Acceleration of TiO2-catalyzed oil upgrading in microdroplets
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430569100446
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Laser desorption/ ionization droplet delivery mass spectrometry for live single cell analysis and imaging
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430568500707
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Accelerated biomolecular kinetics revealed by microdroplet fusion mass spectrometry
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430568501319
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Possible prebiotic fabrication of ribonucleotides using microdroplets
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430568500795
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Can microdroplets catalyze chemical reactions?
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430569103668
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Mechanistic elucidation of Pd-catalyzed reactions using high resolution electrospray ionization mass spectrometry
AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430569103308
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Diagnosis of prostate cancer by desorption electrospray ionization mass spectrometric imaging of small metabolites and lipids
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2017; 114 (13): 3334-3339
Abstract
Accurate identification of prostate cancer in frozen sections at the time of surgery can be challenging, limiting the surgeon's ability to best determine resection margins during prostatectomy. We performed desorption electrospray ionization mass spectrometry imaging (DESI-MSI) on 54 banked human cancerous and normal prostate tissue specimens to investigate the spatial distribution of a wide variety of small metabolites, carbohydrates, and lipids. In contrast to several previous studies, our method included Krebs cycle intermediates (m/z <200), which we found to be highly informative in distinguishing cancer from benign tissue. Malignant prostate cells showed marked metabolic derangements compared with their benign counterparts. Using the "Least absolute shrinkage and selection operator" (Lasso), we analyzed all metabolites from the DESI-MS data and identified parsimonious sets of metabolic profiles for distinguishing between cancer and normal tissue. In an independent set of samples, we could use these models to classify prostate cancer from benign specimens with nearly 90% accuracy per patient. Based on previous work in prostate cancer showing that glucose levels are high while citrate is low, we found that measurement of the glucose/citrate ion signal ratio accurately predicted cancer when this ratio exceeds 1.0 and normal prostate when the ratio is less than 0.5. After brief tissue preparation, the glucose/citrate ratio can be recorded on a tissue sample in 1 min or less, which is in sharp contrast to the 20 min or more required by histopathological examination of frozen tissue specimens.
View details for DOI 10.1073/pnas.1700677114
View details for Web of Science ID 000397607300049
View details for PubMedID 28292895
View details for PubMedCentralID PMC5380053
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Two New Devices for Identifying Electrochemical Reaction Intermediates with Desorption Electrospray Ionization Mass Spectrometry.
Analytical chemistry
2017; 89 (5): 3191-3198
Abstract
Desorption electrospray ionization mass spectrometry (DESI-MS) previously has been used to capture and identify transient intermediates in electrochemical redox reactions on a platinum-covered rotating waterwheel. We present here two different setups that use a flat surface with porous carbon tape as the working electrode, where analyte-containing microdroplets from the DESI probe contacted with electrolyte supplied onto the surface. One setup had the conducting carbon tape in the form of a grooved inclined plane; the other one was in the form of a flat plane that had the conducting carbon tape as its front surface. Both these setups, which were relatively robust and easy to operate, overcame interference from the electrospray sheath gas that disturbs and dries the flowing electrolyte. By using the inclined-plane device, we observed radical cations and dimer species generated in the electrochemical oxidation of triphenylamine, diimine and imine alcohol in the electrochemical oxidation of uric acid, and the reductive cleavage of disulfide bonds in glutathione disulfide. By using the device with the flat carbon tape, we detected nitrenium ions generated in the electrochemical oxidation of N,N'-dimethyoxydiphenylamine and di-p-tolylamine. Our experience suggests that the flat porous carbon tape surface might be preferable over the inclined plane because of its ease of setup.
View details for DOI 10.1021/acs.analchem.6b05124
View details for PubMedID 28193008
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Two-Phase Reactions in Microdroplets without the Use of Phase-Transfer Catalysts.
Angewandte Chemie (International ed. in English)
2017
Abstract
Many important chemical transformations occur in two-phase reactions, which are widely used in chemical, pharmaceutical, and polymer manufacturing. We present an efficient method for performing two-phase reactions in microdroplets sheared by sheath gas without using a phase-transfer catalyst. This avoids disadvantages such as thermal instability, high cost, and, especially, the need to separate and recycle the catalysts. We show that various alcohols can be oxidized to the corresponding aldehydes and ketones within milliseconds in moderate to good yields (50-75 %). The scale-up of the present method was achieved at an isolated rate of 1.2 mg min(-1) for the synthesis of 4-nitrobenzylaldehyde from 4-nitrobenzyl alcohol in the presence of sodium hypochlorite. The biphasic nature of this process, which avoids use of a phase-transfer catalyst, greatly enhances synthetic effectiveness.
View details for DOI 10.1002/anie.201612308
View details for PubMedID 28225181
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Microdroplet fusion mass spectrometry: accelerated kinetics of acid-induced chlorophyll demetallation
QUARTERLY REVIEWS OF BIOPHYSICS
2017; 50: 1-7
Abstract
Kinetics of acid-induced chlorophyll demetallation was recorded in microdroplets by fusing a stream of microdroplets containing 40 µM chlorophyll a or b dissolved in methanol with a stream of aqueous microdroplets containing 35 mM hydrochloric acid (pH = 1·46). The kinetics of the demetallation of chlorophyll in the fused microdroplets (14 ± 6 µm diameter; 84 ± 18 m s-1 velocity) was recorded by controlling the traveling distance of the fused microdroplets between the fusion region and the inlet of a mass spectrometer. The rate of acid-induced chlorophyll demetallation was about 960 ± 120 times faster in the charged microdroplets compared with that reported in bulk solution. If no voltage was applied to the sprayed microdroplets, then the acceleration factor was about 580 ± 90, suggesting that the applied voltage is not a major factor determining the acceleration. Chlorophyll a was more rapidly demetallated than chlorophyll b by a factor of ~26 in bulk solution and ~5 in charged microdroplets. The demetallation kinetics was second order in the H+ concentration, but the acceleration factor of microdroplets compared with bulk solution appeared to be unchanged in going from pH = 1·3 to 7·0. The water:methanol ratio of the fused microdroplets was varied from 7:3 to 3:7 causing an increase in the reaction rate of chlorophyll a demetallation by 20%. This observation demonstrates that the solvent composition, which has different evaporation rates, does not significantly affect the acceleration. We believe that a major portion of the acceleration can be attributed to confinement effects involving surface reactions rather than either to evaporation of solvents or to the introduction of charges to the microdroplets.
View details for DOI 10.1017/S0033583517000014
View details for Web of Science ID 000396422700001
View details for PubMedCentralID PMC5729759
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Personal Information from Latent Fingerprints Using Desorption Electrospray Ionization Mass Spectrometry and Machine Learning
ANALYTICAL CHEMISTRY
2017; 89 (2): 1369-1372
Abstract
Desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) was applied to latent fingerprints to obtain not only spatial patterns but also chemical maps. Samples with similar lipid compositions as those of the fingerprints were collected by swiping a glass slide across the forehead of consenting adults. A machine learning model called gradient boosting tree ensemble (GDBT) was applied to the samples that allowed us to distinguish between different genders, ethnicities, and ages (within 10 years). The results from 194 samples showed accuracies of 89.2%, 82.4%, and 84.3%, respectively. Specific chemical species that were determined by the feature selection of GDBT were identified by tandem mass spectrometry. As a proof-of-concept, the machine learning model trained on the sample data was applied to overlaid latent fingerprints from different individuals, giving accurate gender and ethnicity information from those fingerprints. The results suggest that DESI-MSI imaging of fingerprints with GDBT analysis might offer a significant advance in forensic science.
View details for DOI 10.1021/acs.analchem.6b04498
View details for Web of Science ID 000392458100047
View details for PubMedID 28194988
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Mechanistic analysis of a copper-catalyzed C-H oxidative cyclization of carboxylic acids.
Chemical science
2017; 8 (10): 7003–8
Abstract
We recently reported that carboxylic acids can be oxidized to lactone products by potassium persulfate and catalytic copper acetate. Here, we unravel the mechanism for this C-H functionalization reaction using desorption electrospray ionization, online electrospray ionization, and tandem mass spectrometry. Our findings suggest that electron transfer from a transient benzylic radical intermediate reduces Cu(ii) to Cu(i), which is then re-oxidized to Cu(ii) in the catalytic cycle. The resulting benzylic carbocation is trapped by the pendant carboxylate group to give the lactone product. Formation of the putative benzylic carbocation is supported by Hammett analysis. The proposed mechanism for this copper-catalyzed oxidative cyclization process differs from earlier reports of analogous reactions, which posit a substrate carboxylate radical as the reactive oxidant.
View details for PubMedID 29147527
View details for PubMedCentralID PMC5642147
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Polymer-spray mass spectrometric detection and quantitation of hydrophilic compounds and some narcotics.
Rapid communications in mass spectrometry : RCM
2017; 31 (19): 1651–58
Abstract
High-throughput screening of biofluids is essential in monitoring concentration of a variety of drugs to determine their efficacy and toxicity. Organosiloxane polymers prepared by sol-gel chemistry as sample supports, and electrospray ionization emitters in a single material and as an alternative to paper substrates, is described in this study.Hydrophobic drugs and hydrophilic streptomycin were analyzed by polymer-spray mass spectrometry with an LTQ-Orbitrap mass spectrometer. Drug samples in urine (1-2 μL) were deposited on an OSX polymer, allowed to dry, then electrosprayed from the polymer tip into the mass spectrometer without sample pretreatment. The OSX polymers, whose polarity and porosity can be controlled, were prepared by sol-gel chemistry where methyl-substituted alkoxysilanes were hydrolyzed in the presence of a pore template and an acid catalyst.Five nanograms each of seven narcotic drugs were detected in <1 min (relative standard deviation (RSD) of response <1% for each drug). Calibration curves of cocaine and streptomycin in urine were used to establish the performance of the polymer. For sample 1 (n = 2), the mean recovery for cocaine was 81% with paper and 90% with polymer. Streptomycin is detected with polymer, not with paper; for samples 1 and 2 (n = 3), mean recovery was 97% and 95%, respectively.Organosiloxane polymers achieve more sensitive analysis than paper, allowing for more accurate quantitation of both hydrophobic and hydrophilic drug compounds. The ability to tailor the polymer polarity and porosity allows for the synthesis of a wide range of polymers, and thus opens many possibilities for further development and applications.
View details for PubMedID 28792093
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Quantum control of molecular collisions at 1 kelvin.
Science (New York, N.Y.)
2017; 358 (6361): 356–59
Abstract
Measurement of vector correlations in molecular scattering is an indispensable tool for mapping out interaction potentials. In a coexpanded supersonic beam, we have studied the rotationally inelastic process wherein deuterium hydride (HD) (v = 1, j = 2) collides with molecular deuterium (D2) to form HD (v = 1, j = 1), where v and j are the vibrational and rotational quantum numbers, respectively. HD (v = 1, j = 2) was prepared by Stark-induced adiabatic Raman passage, with its bond axis aligned preferentially parallel or perpendicular to the lab-fixed relative velocity. The coexpansion brought the collision temperature down to 1 kelvin, restricting scattering to s and p partial waves. Scattering angular distributions showed a dramatic stereodynamic preference (~3:1) for perpendicular versus parallel alignment. The four-vector correlation measured between the initial and final velocities and the initial and final rotational angular momentum vectors of HD provides insight into the strong anisotropic forces present in the collision process.
View details for PubMedID 29051378
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Microdroplet fusion mass spectrometry: accelerated kinetics of acid-induced chlorophyll demetallation.
Quarterly reviews of biophysics
2017; 50: e2
Abstract
Kinetics of acid-induced chlorophyll demetallation was recorded in microdroplets by fusing a stream of microdroplets containing 40 µM chlorophyll a or b dissolved in methanol with a stream of aqueous microdroplets containing 35 mM hydrochloric acid (pH = 1·46). The kinetics of the demetallation of chlorophyll in the fused microdroplets (14 ± 6 µm diameter; 84 ± 18 m s-1 velocity) was recorded by controlling the traveling distance of the fused microdroplets between the fusion region and the inlet of a mass spectrometer. The rate of acid-induced chlorophyll demetallation was about 960 ± 120 times faster in the charged microdroplets compared with that reported in bulk solution. If no voltage was applied to the sprayed microdroplets, then the acceleration factor was about 580 ± 90, suggesting that the applied voltage is not a major factor determining the acceleration. Chlorophyll a was more rapidly demetallated than chlorophyll b by a factor of ~26 in bulk solution and ~5 in charged microdroplets. The demetallation kinetics was second order in the H+ concentration, but the acceleration factor of microdroplets compared with bulk solution appeared to be unchanged in going from pH = 1·3 to 7·0. The water:methanol ratio of the fused microdroplets was varied from 7:3 to 3:7 causing an increase in the reaction rate of chlorophyll a demetallation by 20%. This observation demonstrates that the solvent composition, which has different evaporation rates, does not significantly affect the acceleration. We believe that a major portion of the acceleration can be attributed to confinement effects involving surface reactions rather than either to evaporation of solvents or to the introduction of charges to the microdroplets.
View details for DOI 10.1017/S0033583517000014
View details for PubMedID 29233214
View details for PubMedCentralID PMC5729759
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Abiotic production of sugar phosphates and uridine ribonucleoside in aqueous microdroplets.
Proceedings of the National Academy of Sciences of the United States of America
2017; 114 (47): 12396–400
Abstract
Phosphorylation is an essential chemical reaction for life. This reaction generates fundamental cell components, including building blocks for RNA and DNA, phospholipids for cell walls, and adenosine triphosphate (ATP) for energy storage. However, phosphorylation reactions are thermodynamically unfavorable in solution. Consequently, a long-standing question in prebiotic chemistry is how abiotic phosphorylation occurs in biological compounds. We find that the phosphorylation of various sugars to form sugar-1-phosphates can proceed spontaneously in aqueous microdroplets containing a simple mixture of sugars and phosphoric acid. The yield for d-ribose-1-phosphate reached over 6% at room temperature, giving a ΔGvalue of -1.1 kcal/mol, much lower than the +5.4 kcal/mol for the reaction in bulk solution. The temperature dependence of the product yield for the phosphorylation in microdroplets revealed a negative enthalpy change (ΔH= -0.9 kcal/mol) and a negligible change of entropy (ΔS= 0.0007 kcal/mol·K). Thus, the spontaneous phosphorylation reaction in microdroplets occurred by overcoming the entropic hurdle of the reaction encountered in bulk solution. Moreover, uridine, a pyrimidine ribonucleoside, is generated in aqueous microdroplets containing d-ribose, phosphoric acid, and uracil, which suggests the possibility that microdroplets could serve as a prebiotic synthetic pathway for ribonucleosides.
View details for PubMedID 29078402
View details for PubMedCentralID PMC5703324
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Electrically controlled release of insulin using polypyrrole nanoparticles
NANOSCALE
2017; 9 (1): 143-149
Abstract
Conducting polymers present an opportunity for developing programmable, adjustable, spatially, and temporally controllable drug delivery systems. While several small molecule drugs have been released from thin conductive polymeric films successfully, delivering large molecule therapeutics, such as polypeptides and nucleic acids, has remained a significant challenge. Poor drug loading (∼ng cm(-2)) of thin films coupled with film instability has, in many cases, made conducting polymer films refractory to clinical development. To address these limitations, we have utilized conductive polymer nanoparticulate backbones to controllably release insulin, a high molecular weight, clinically relevant polypeptide. We find that the interaction between insulin and the polymer scaffold can be described by a simple Langmuir-type adsorption model. By modifying the ratio of the amount of nanoparticles to the amount of insulin, we have obtained drug loading percentages estimated to be as high as 51 wt% percent. In vivo experiments in mice confirmed retained bioactivity of the released insulin after electrical stimulation.
View details for DOI 10.1039/c6nr08288b
View details for Web of Science ID 000391739300020
View details for PubMedID 27929180
View details for PubMedCentralID PMC5215613
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Preparation of a selected high vibrational energy level of isolated molecules.
journal of chemical physics
2016; 145 (15): 154203-?
Abstract
Stark induced adiabatic Raman passage (SARP) allows us to prepare an appreciable concentration of isolated molecules in a specific, high-lying vibrational level. The process has general applicability, and, as a demonstration, we transfer nearly 100 percent of the HD (v = 0, J = 0) in a supersonically expanded molecular beam of HD molecules to HD (v = 4, J = 0). This is achieved with a sequence of partially overlapping nanosecond pump (355 nm) and Stokes (680 nm) single-mode laser pulses of unequal intensities. By comparing our experimental data with our theoretical calculations, we are able to draw two important conclusions: (1) using SARP a large population (>10(10) molecules per laser pulse) is prepared in the (v = 4, J = 0) level of HD and (2) the polarizability α00,40 (≅0.6 × 10(-41) C m(2) V(-1)) for the (v = 0, J = 0) to (v = 4, J = 0) Raman overtone transition is only about five times smaller than α00,10 for the (v = 0, J = 0) to (v = 1, J = 0) fundamental Raman transition. Moreover, the SARP process selects a specific rotational level in the vibrational manifold and can prepare one or a phased linear combination of magnetic sublevels (M states) within the selected vibrational-rotational level. This capability of preparing selected, highly excited vibrational levels of molecules under collision-free conditions opens new opportunities for fundamental scattering experiments.
View details for PubMedID 27782486
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A Study of Heterogeneous Catalysis by Nanoparticle-Embedded Paper-Spray Ionization Mass Spectrometry.
Angewandte Chemie (International ed. in English)
2016; 55 (41): 12807-12811
Abstract
We have developed nanoparticle-embedded paper-spray mass spectrometry for studying three types of heterogeneously catalyzed reactions: 1) Palladium-nanoparticle-catalyzed Suzuki cross-coupling reactions, 2) palladium- or silver-nanoparticle-catalyzed 4-nitrophenol reduction, and 3) gold-nanoparticle-catalyzed glucose oxidation. These reactions were almost instantaneous on the nanocatalyst-embedded paper, which subsequently transferred the transient intermediates and products to a mass spectrometer for their detection. This in situ method of capturing transient intermediates and products from heterogeneous catalysis is highly promising for investigating the mechanism of catalysis and rapidly screening catalytic activity under ambient conditions.
View details for DOI 10.1002/anie.201607204
View details for PubMedID 27633445
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Impact of Laboratory-Induced Thermal Maturity on Asphaltene Molecular Structure
ENERGY & FUELS
2016; 30 (9): 7025-7036
View details for DOI 10.1021/acs.energyfuels.6b01238
View details for Web of Science ID 000383641000017
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Catalytic Carbonylative Spirolactonization of Hydroxycyclopropanols.
Journal of the American Chemical Society
2016; 138 (33): 10693-10699
Abstract
A palladium-catalyzed cascade carbonylative spirolactonization of hydroxycyclopropanols has been developed to efficiently synthesize oxaspirolactones common to many complex natural products of important therapeutic value. The mild reaction conditions, high atom economy, broad substrate scope, and scalability of this new method were highlighted in expedient total syntheses of the Turkish tobacco natural products α-levantanolide and α-levantenolide in two and four steps, respectively. The hydroxycyclopropanol substrates are readily available in one step via a Kulinkovich reaction of the corresponding lactones. Mechanistic studies utilizing high-resolution electrospray ionization mass spectrometry (ESI-MS) identified several key intermediates in the catalytic cycle, as well as those related to catalyst decomposition and competitive pathways.
View details for DOI 10.1021/jacs.6b06573
View details for PubMedID 27459274
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Experimental investigations of the decomposition of ionic liquids
AMER CHEMICAL SOC. 2016
View details for Web of Science ID 000431460402730
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Electrically controlled drug delivery
AMER CHEMICAL SOC. 2016
View details for Web of Science ID 000431460200750
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Direct Copper(III) Formation from O2 and Copper(I) with Histamine Ligation.
Journal of the American Chemical Society
2016; 138 (31): 9986-9995
Abstract
Histamine chelation of copper(I) by a terminal histidine residue in copper hydroxylating enzymes activates dioxygen to form unknown oxidants, generally assumed as copper(II) species. The direct formation of copper(III)-containing products from the oxygenation of histamine-ligated copper(I) complexes is demonstrated here, indicating that copper(III) is a viable oxidation state in such products from both kinetic and thermodynamic perspectives. At low temperatures, both trinuclear Cu(II)2Cu(III)O2 and dinuclear Cu(III)2O2 predominate, with the distribution dependent on the histamine ligand structure and oxygenation conditions. Kinetics studies suggest the bifurcation point to these two products is an unobserved peroxide-level dimer intermediate. The hydrogen atom reactivity difference between the trinuclear and binuclear complexes at parity of histamine ligand is striking. This behavior is best attributed to the accessibility of the bridging oxide ligands to exogenous substrates rather than a difference in oxidizing abilities of the clusters.
View details for DOI 10.1021/jacs.6b05538
View details for PubMedID 27467215
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Miniaturized Linear Wire Ion Trap Mass Analyzer
ANALYTICAL CHEMISTRY
2016; 88 (15): 7800-7806
Abstract
We report a linear ion trap (LIT) in which the electric field is formed by fine wires held under tension and accurately positioned using holes drilled in two end plates made of plastic. The coordinates of the hole positions were optimized in simulation. The stability diagram and mass spectra using boundary ejection were compared between simulation and experiment and good agreement was found. The mass spectra from experiments show peak widths (fwhm) in units of mass-to-charge of around 0.38 Th using a scan rate of 3830 Th/s. The limits of detection are 137 ppbv and 401 ppbv for benzene and toluene, respectively. Different sizes of the wire ion trap can be easily fabricated by drilling holes in scaled positions. Other distinguishing features, such as high ion and photon transmission, low capacitance, high tolerance to mechanical and assembly error, and low weight, are discussed.
View details for DOI 10.1021/acs.analchem.6b01830
View details for PubMedID 27373557
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Scaffold-mediated BMP-2 minicircle DNA delivery accelerated bone repair in a mouse critical-size calvarial defect model
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
2016; 104 (8): 2099-2107
Abstract
Scaffold-mediated gene delivery holds great promise for tissue regeneration. However, previous attempts to induce bone regeneration using scaffold-mediated non-viral gene delivery rarely resulted in satisfactory healing. We report a novel platform with sustained release of minicircle DNA (MC) from PLGA scaffolds to accelerate bone repair. MC was encapsulated inside PLGA scaffolds using supercritical CO2 , which showed prolonged release of MC. Skull-derived osteoblasts transfected with BMP-2 MC in vitro result in higher osteocalcin gene expression and mineralized bone formation. When implanted in a critical-size mouse calvarial defect, scaffolds containing luciferase MC lead to robust in situ protein production up to at least 60 days. Scaffold-mediated BMP-2 MC delivery leads to substantially accelerated bone repair as early as two weeks, which continues to progress over 12 weeks. This platform represents an efficient, long-term nonviral gene delivery system, and may be applicable for enhancing repair of a broad range of tissues types. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2099-2107, 2016.
View details for DOI 10.1002/jbm.a.35735
View details for Web of Science ID 000379736500025
View details for PubMedID 27059085
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Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging.
PLoS medicine
2016; 13 (8)
Abstract
Surgical resection with microscopically negative margins remains the main curative option for pancreatic cancer; however, in practice intraoperative delineation of resection margins is challenging. Ambient mass spectrometry imaging has emerged as a powerful technique for chemical imaging and real-time diagnosis of tissue samples. We applied an approach combining desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with the least absolute shrinkage and selection operator (Lasso) statistical method to diagnose pancreatic tissue sections and prospectively evaluate surgical resection margins from pancreatic cancer surgery.Our methodology was developed and tested using 63 banked pancreatic cancer samples and 65 samples (tumor and specimen margins) collected prospectively during 32 pancreatectomies from February 27, 2013, to January 16, 2015. In total, mass spectra for 254,235 individual pixels were evaluated. When cross-validation was employed in the training set of samples, 98.1% agreement with histopathology was obtained. Using an independent set of samples, 98.6% agreement was achieved. We used a statistical approach to evaluate 177,727 mass spectra from samples with complex, mixed histology, achieving an agreement of 81%. The developed method showed agreement with frozen section evaluation of specimen margins in 24 of 32 surgical cases prospectively evaluated. In the remaining eight patients, margins were found to be positive by DESI-MSI/Lasso, but negative by frozen section analysis. The median overall survival after resection was only 10 mo for these eight patients as opposed to 26 mo for patients with negative margins by both techniques. This observation suggests that our method (as opposed to the standard method to date) was able to detect tumor involvement at the margin in patients who developed early recurrence. Nonetheless, a larger cohort of samples is needed to validate the findings described in this study. Careful evaluation of the long-term benefits to patients of the use of DESI-MSI for surgical margin evaluation is also needed to determine its value in clinical practice.Our findings provide evidence that the molecular information obtained by DESI-MSI/Lasso from pancreatic tissue samples has the potential to transform the evaluation of surgical specimens. With further development, we believe the described methodology could be routinely used for intraoperative surgical margin assessment of pancreatic cancer.
View details for DOI 10.1371/journal.pmed.1002108
View details for PubMedID 27575375
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Multiple scattering mechanisms causing interference effects in the differential cross sections of H + D2 ? HD(v' = 4, ?j') + D at 3.26 eV collision energy.
journal of chemical physics
2016; 145 (2): 024308-?
Abstract
Differential cross sections (DCSs) for the H + D2 → HD(v' = 4, j') + D reaction at 3.26 eV collision energy have been measured using the photoloc technique, and the results have been compared with those from quantum and quasiclassical scattering calculations. The quantum mechanical DCSs are in good overall agreement with the experimental measurements. In common with previous results at 1.97 eV, clear interference patterns which appear as fingerlike structures have been found at 3.26 eV but in this case for vibrational states as high as v' = 4. The oscillatory structure is prominent for low rotational states and progressively disappears as j' increases. A detailed analysis, similar to that carried out at 1.97 eV, shows that the origin of these structures could be traced to interferences between well defined classical mechanisms. In addition, at this energy, we do not observe the anomalous positive j'-θ trend found for the v' = 4 manifold at lower collision energies, thus reinforcing our explanation that the anomalous distribution for HD(v' = 4, j') at 1.97 eV only takes place for those states associated with low product recoil energies.
View details for DOI 10.1063/1.4955294
View details for PubMedID 27421406
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Monitoring Enzymatic Reactions in Real Time Using Venturi Easy Ambient Sonic-Spray Ionization Mass Spectrometry
ANALYTICAL CHEMISTRY
2016; 88 (12): 6195-6198
Abstract
We developed a technique to monitor spatially confined surface reactions with mass spectrometry under ambient conditions, without the need for voltage or organic solvents. Fused-silica capillaries immersed in an aqueous solution, positioned in close proximity to each other and the functionalized surface, created a laminar flow junction with a resulting reaction volume of ∼5 pL. The setup was operated with a syringe pump, delivering reagents to the surface through a fused-silica capillary. The other fused-silica capillary was connected to a Venturi easy ambient sonic-spray ionization source, sampling the resulting analytes at a slightly higher flow rate compared to the feeding capillary. The combined effects of the inflow and outflow maintains a chemical microenvironment, where the rate of advective transport overcomes diffusion. We show proof-of-concept where acetylcholinesterase was immobilized on an organosiloxane polymer through electrostatic interactions. The hydrolysis of acetylcholine by acetylcholinesterase into choline was monitored in real-time for a range of acetylcholine concentrations, fused-silica capillary geometries, and operating flow rates. Higher reaction rates and conversion yields were observed with increasing acetylcholine concentrations, as would be expected.
View details for DOI 10.1021/acs.analchem.6b01246
View details for Web of Science ID 000378470200019
View details for PubMedID 27249533
View details for PubMedCentralID PMC4917919
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Angular and internal state distributions of H-2(+) generated by (2+1) resonance enhanced multiphoton ionization of H-2 using time-of-flight mass spectrometry
JOURNAL OF CHEMICAL PHYSICS
2016; 144 (21)
Abstract
We report direct measurement of the anisotropy parameter β for the angular distribution of the photoelectron and photoion in (2 + 1) resonance enhanced multiphoton ionization process of H2 X (1)Σg (+) (v = 0, J = 0) molecules through the intermediate H2 E,F (1)Σg (+) (v' = 0, J' = 0) level (λ = 201.684 nm) using a time-of-flight mass spectrometer. The time-of-flight spectra were recorded as the direction of polarization of the ionizing laser was varied with respect to the flight axis of the H2 molecular beam and were fitted to an angular distribution in an appropriately rotated coordinate system with the z-axis oriented along the time-of-flight axis. The anisotropy parameter β was found to be 1.72 ± 0.13 by fitting the time-of-flight spectra and agreed with previous measurements. Using secondary ionization with a delayed laser pulse of different wavelength, we also determined the vibrational energy distribution of the ions, showing that 98% ± 4% of the ions are generated in their ground vibrational state, in agreement with the calculated Franck-Condon factors between the H2 E,F (1)Σg (+) (v' = 0) and H2 (+) X (1)Σg (+) (v″) vibrational levels.
View details for DOI 10.1063/1.4952759
View details for Web of Science ID 000378923500013
View details for PubMedID 27276949
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High-Resolution Live-Cell Imaging and Analysis by Laser Desorption/Ionization Droplet Delivery Mass Spectrometry
ANALYTICAL CHEMISTRY
2016; 88 (10): 5453-5461
Abstract
We have developed a new ambient-ionization mass spectrometric technique named laser desorption/ionization droplet delivery mass spectrometry (LDIDD-MS). LDIDD-MS permitted high-resolution, high-sensitivity imaging of tissue samples as well as measurement of both single-cell apoptosis and live-cell exocytosis. A pulsed (15 Hz) UV laser beam (266 nm) was focused on a surface covered with target analytes to trigger their desorption and ionization. A spray of liquid droplets was simultaneously directed onto the laser-focused surface region to capture the ionized analytes and deliver them to a mass spectrometer. The approach of rapid and effective capturing molecules after laser desorption/ionization allowed the limit of detection for the amino acid lysine to be as low as 2 amol under ambient ionization conditions. Two-dimensional maps of the desorbed/ionized species were recorded by moving the sample on an XY translational stage. The spatial resolution for imaging with LDIDD-MS was determined to be 2.4 µm for an ink-printed pattern and 3 µm for mouse brain tissue. We applied LDIDD-MS to single-cell analysis of apoptotic HEK cells. Differences were observed in the profiles of fatty acids and lipids between healthy HEK cells and those undergoing apoptosis: We observed the upregulation of phosphatidylcholine (PC) with a relatively shorter carbon chain length and downregulation of PC with a relatively longer carbon chain length. We also applied LDIDD-MS for a real-time direct measurement of live-cell exocytosis. The catecholamine dopamine and trace amines (phenethylamine and tyramine) were detected from live PC12 cells without damaging them.
View details for DOI 10.1021/acs.analchem.6b00881
View details for Web of Science ID 000376223500059
View details for PubMedID 27110027
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Nanotip Ambient Ionization Mass Spectrometry
ANALYTICAL CHEMISTRY
2016; 88 (10): 5542-5548
Abstract
A method called nanotip ambient ionization mass spectrometry (NAIMS) is described, which applies high voltage between a tungsten nanotip and a metal plate to generate a plasma in which ionized analytes on the surface of the metal plate are directed to the inlet and analyzed by a mass spectrometer. The dependence of signal intensity is investigated as a function of the tip-to-plate distance, the tip size, the voltage applied at the tip, and the current. These parameters are separately optimized to achieve sensitivity or high spatial resolution. A partially observable Markov decision process is used to achieve a stabilized plasma as well as high ionization efficiency. As a proof of concept, the NAIMS technique has been applied to phenanthrene and caffeine samples for which the limits of detection were determined to be 0.14 fmol for phenanthrene and 4 amol for caffeine and to a printed caffeine pattern for which a spatial resolution of 8 ± 2 μm, and the best resolution of 5 μm, was demonstrated. The limitations of NAIMS are also discussed.
View details for DOI 10.1021/acs.analchem.6b01212
View details for Web of Science ID 000376223500071
View details for PubMedID 27087600
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Molecular Dynamics Simulation of beta-Lactoglobulin at Different Oil/Water Interfaces
BIOMACROMOLECULES
2016; 17 (5): 1572-1581
Abstract
Controlling and manipulating protein behavior at an interface is of immense relevance to a broad range of physicochemical and biological phenomena and technological processes. Although many experimental studies have contributed to rapid progress in the fundamental knowledge of protein behavior at interfaces, detailed molecular-level understanding of the mechanism of protein adsorption at an interface is still remarkably lacking. In this study, atomistic molecular dynamics simulations were used to characterize the adsorption of β-lactoglobulin at two different oil/water (O/W) interfaces, where the oil was either the marginally hydrophilic octanol or the more hydrophilic triolein, and the results were compared to those of a previous study utilizing the hydrophobic oil decane. Both the approach to the surface and the mechanism of adsorption depend upon the hydrophilicity of the oil and the interfacial tension of the O/W interface, with the nature of the adsorption, the accompanying structural changes, and the energetic driving force differing markedly between the different oils. Intriguingly, the behavior of the protein resembles that predicted for a soft spherical particle at an O/W interface. The results are also in agreement with key experimental findings, particularly the observation that proteins undergo more conformational change upon adsorption to hydrophobic surfaces, flattening out to expose hydrophobic interior residues to the surface, and that a thicker layer of native-like adsorbed protein forms at hydrophilic surfaces, and reveal structural and mechanistic detail behind each mechanism of adsorption.
View details for DOI 10.1021/acs.biomac.5b01709
View details for Web of Science ID 000375886500003
View details for PubMedID 27075297
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Fall and Rise of a D2O Ice Cube in Liquid H2O
RESONANCE-JOURNAL OF SCIENCE EDUCATION
2016; 21 (5): 453-456
View details for Web of Science ID 000376532100009
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IISERs
CURRENT SCIENCE
2016; 110 (7): 1137
View details for Web of Science ID 000373347000005
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My life with lasers
AMER CHEMICAL SOC. 2016
View details for Web of Science ID 000431905707376
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Using mass spectrometry to identify short-lived electrochemical reaction intermediates
AMER CHEMICAL SOC. 2016
View details for Web of Science ID 000431903800430
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Effects of reagent rotation on interferences in the product angular distributions of chemical reactions
CHEMICAL SCIENCE
2016; 7 (1): 642-649
View details for DOI 10.1039/c5sc03373j
View details for Web of Science ID 000366826900076
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An Ultrasonically Powered Implantable Device for Targeted Drug Delivery
IEEE. 2016: 541–44
Abstract
A wirelessly powered implantable device is proposed for fully programmable and localized drug delivery. The implant is powered using an external ultrasonic transmitter and operates at <; 5% of the FDA diagnostic ultrasound intensity limit. Drug release is achieved through electrical stimulation of drug-loaded polypyrrole nanoparticles. A design methodology for the implant electronics is presented and experimentally demonstrated to be accurate in predicting the concentration of the released drug. To the best of our knowledge, this is the first ultrasonically powered implantable device platform for targeted drug delivery using electroresponsive polymers. The active area of the implant electronics is just 3 mm × 5 mm.
View details for Web of Science ID 000399823500133
View details for PubMedID 28324933
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Observation of electrochemically generated nitrenium ions by desorption electrospray ionization mass spectrometry.
Chemical science
2016; 7 (1): 329-332
Abstract
We report the observation of the electrochemically generated nitrenium ions of 4,4'-dimethyoxydiphenylamine and di-p-tolylamine in solution by mass spectrometry. This setup takes inspiration from desorption electrospray ionization mass spectrometry to sample directly from the surface of a rotating waterwheel working electrode for mass spectrometric analysis. Detection of the 4,4'-dimethyoxydiphenylamine nitrenium ion was expected based upon para-methoxy resonance stabilization, whereas observation of the di-p-tolylamine nitrenium ion might be unexpected because resonance stabilization from the para-substituted position is unavailable. However, the short timescale analysis of the setup allows for the isolation of the di-p-tolylamine nitrenium ion, which is electrogenerated in solution and detected mass spectrometrically.
View details for DOI 10.1039/c5sc02939b
View details for PubMedID 28791096
View details for PubMedCentralID PMC5518571
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Going beyond electrospray: mass spectrometric studies of chemical reactions in and on liquids.
Chemical science
2016; 7 (1): 39-55
Abstract
There has been a burst in the number and variety of available ionization techniques to use mass spectrometry to monitor chemical reactions in and on liquids. Chemists have gained the capability to access chemistry at unprecedented timescales, and monitor reactions and detect intermediates under almost any set of conditions. Herein, recently developed ionization techniques that facilitate mechanistic studies of chemical processes are reviewed. This is followed by a discussion of our perspective on the judicious application of these and similar techniques in order to study reaction mechanisms.
View details for DOI 10.1039/c5sc02740c
View details for PubMedID 28757996
View details for PubMedCentralID PMC5508663
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Better Practices in Scientific Publishing.
Angewandte Chemie (International ed. in English)
2016; 55 (8): 2606–7
View details for PubMedID 26799244
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Electroresponsive nanoparticles for drug delivery on demand
NANOSCALE
2016; 8 (17): 9310-9317
Abstract
The potential of electroresponsive conducting polymer nanoparticles to be used as general drug delivery systems that allow electrically pulsed, linearly scalable, and on demand release of incorporated drugs is demonstrated. As examples, facile release from polypyrrole nanoparticles is shown for fluorescein, a highly water-soluble model compound, piroxicam, a lipophilic small molecule drug, and insulin, a large hydrophilic peptide hormone. The drug loading is about 13 wt% and release is accomplished in a few seconds by applying a weak constant current or voltage. To identify the parameters that should be finely tuned to tailor the carrier system for the release of the therapeutic molecule of interest, a systematic study of the factors that affect drug delivery is performed, using fluorescein as a model compound. The parameters studied include current, time, voltage, pH, temperature, particle concentration, and ionic strength. Results indicate that there are several degrees of freedom that can be optimized for efficient drug delivery. The ability to modulate linearly drug release from conducting polymers with the applied stimulus can be utilized to design programmable and minimally invasive drug delivery devices.
View details for DOI 10.1039/c6nr01884j
View details for Web of Science ID 000375285800029
View details for PubMedID 27088543
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Performance of chemically modified plastic blood collection tubes
CLINICAL BIOCHEMISTRY
2016; 49 (1-2): 90-99
Abstract
The objective of this study was to compare newly-modified and aged chemoPET tubes, which contain no problematic surfactants, with commercially available serum blood collection tubes (BCTs) for use in analysis of cortisol, total triiodothyronine (TT3), total thyroxine (TT4), and routine clinical chemistry analytes in serum from apparently healthy volunteers and pooled quality control (QC) specimens.Blood specimens collected from 60 apparently healthy volunteers (18 males, 42 females) and pooled QC specimens poured into seven different BCTs were analyzed by a trained phlebotomist. Cortisol, TT3, and TT4 levels were measured on an Immulite 1000 instrument and routine chemistry tests were analyzed on a Siemens RxL instrument. The significance of differences between chemoPET and other BCT types compared to glass tubes were assessed by Student's paired t-test or repeated measures ANOVA or their non-parametric equivalents. The BCT-related biases (deviation from glass tubes) in analyte concentrations were compared with the current desirable allowable bias, derived from biological variation. Serum analyte concentrations in the different BCTs that exceeded their respective significant change limits were considered clinically significant.No statistically and/or clinically significant differences were noted in the analyte concentrations from serum specimens and pooled QC material when our newly modified and aged chemoPET tubes were compared to glass and other BCTs.The chemoPET tubes described here may be a suitable alternative to serum BCTs that contain problematic surfactants known to interfere with some clinical assays on the Immulite 1000 and RxL instruments.
View details for DOI 10.1016/j.clinbiochem.2015.09.003
View details for Web of Science ID 000368752700017
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Performance of chemically modified plastic blood collection tubes.
Clinical biochemistry
2016; 49 (1): 90-99
Abstract
The objective of this study was to compare newly-modified and aged chemoPET tubes, which contain no problematic surfactants, with commercially available serum blood collection tubes (BCTs) for use in analysis of cortisol, total triiodothyronine (TT3), total thyroxine (TT4), and routine clinical chemistry analytes in serum from apparently healthy volunteers and pooled quality control (QC) specimens.Blood specimens collected from 60 apparently healthy volunteers (18 males, 42 females) and pooled QC specimens poured into seven different BCTs were analyzed by a trained phlebotomist. Cortisol, TT3, and TT4 levels were measured on an Immulite 1000 instrument and routine chemistry tests were analyzed on a Siemens RxL instrument. The significance of differences between chemoPET and other BCT types compared to glass tubes were assessed by Student's paired t-test or repeated measures ANOVA or their non-parametric equivalents. The BCT-related biases (deviation from glass tubes) in analyte concentrations were compared with the current desirable allowable bias, derived from biological variation. Serum analyte concentrations in the different BCTs that exceeded their respective significant change limits were considered clinically significant.No statistically and/or clinically significant differences were noted in the analyte concentrations from serum specimens and pooled QC material when our newly modified and aged chemoPET tubes were compared to glass and other BCTs.The chemoPET tubes described here may be a suitable alternative to serum BCTs that contain problematic surfactants known to interfere with some clinical assays on the Immulite 1000 and RxL instruments.
View details for DOI 10.1016/j.clinbiochem.2015.09.003
View details for PubMedID 26375014
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Observation of electrochemically generated nitrenium ions by desorption electrospray ionization mass spectrometry
CHEMICAL SCIENCE
2016; 7 (1): 329-332
Abstract
We report the observation of the electrochemically generated nitrenium ions of 4,4'-dimethyoxydiphenylamine and di-p-tolylamine in solution by mass spectrometry. This setup takes inspiration from desorption electrospray ionization mass spectrometry to sample directly from the surface of a rotating waterwheel working electrode for mass spectrometric analysis. Detection of the 4,4'-dimethyoxydiphenylamine nitrenium ion was expected based upon para-methoxy resonance stabilization, whereas observation of the di-p-tolylamine nitrenium ion might be unexpected because resonance stabilization from the para-substituted position is unavailable. However, the short timescale analysis of the setup allows for the isolation of the di-p-tolylamine nitrenium ion, which is electrogenerated in solution and detected mass spectrometrically.
View details for DOI 10.1039/c5sc02939b
View details for Web of Science ID 000366826900037
View details for PubMedCentralID PMC5518571
-
Going beyond electrospray: mass spectrometric studies of chemical reactions in and on liquids
CHEMICAL SCIENCE
2016; 7 (1): 39-55
Abstract
There has been a burst in the number and variety of available ionization techniques to use mass spectrometry to monitor chemical reactions in and on liquids. Chemists have gained the capability to access chemistry at unprecedented timescales, and monitor reactions and detect intermediates under almost any set of conditions. Herein, recently developed ionization techniques that facilitate mechanistic studies of chemical processes are reviewed. This is followed by a discussion of our perspective on the judicious application of these and similar techniques in order to study reaction mechanisms.
View details for DOI 10.1039/c5sc02740c
View details for Web of Science ID 000366826900002
View details for PubMedCentralID PMC5508663
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Differential Cross Sections for the H + D-2 -> HD(v '=3, j '=4-10) + D Reaction above the Conical Intersection
JOURNAL OF PHYSICAL CHEMISTRY A
2015; 119 (50): 12036-12042
Abstract
We report rovibrationally selected differential cross sections (DCSs) of the benchmark reaction H + D2 → HD(v' = 3, j' = 4-10) + D at a collision energy of 3.26 eV, which exceeds the conical intersection of the H3 potential energy surface at 2.74 eV. We use the PHOTOLOC technique in which a fluorine excimer laser at 157.64 nm photodissociates hydrogen bromide (HBr) molecules to generate fast H atoms and the HD product is detected in a state-specific manner by resonance-enhanced multiphoton ionization. Fully converged quantum wave packet calculations were performed for this reaction at this high collision energy without inclusion of the geometric phase (GP) effect, which takes into account coupling to the first excited state of the H3 potential energy surface. Multimodal structures can be observed in most of the DCSs up to j' = 10, which is predicted by theory and also well-reproduced by experiment. The theoretically calculated DCSs are in good overall agreement with the experimental measurements, which indicates that the GP effect is not large enough that its existence can be verified experimentally at this collision energy.
View details for DOI 10.1021/acs.jpca.5b04573
View details for PubMedID 26090780
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Protein Analysis by Ambient Ionization Mass Spectrometry Using Trypsin-Immobilized Organosiloxane Polymer Surfaces
ANALYTICAL CHEMISTRY
2015; 87 (24): 12324-12330
Abstract
In the growing field of proteomic research, rapid and simple protein analysis is a crucial component of protein identification. We report the use of immobilized trypsin on hybrid organic-inorganic organosiloxane (T-OSX) polymers for the on-surface, in situ digestion of four model proteins: melittin, cytochrome c, myoglobin, and bovine serum albumin. Tryptic digestion products were sampled, detected, and identified using desorption electrospray ionization mass spectrometry (DESI-MS) and nanoDESI-MS. These novel, reusable T-OSX arrays on glass slides allow for protein digestion in methanol:water solvents (1:1, v/v) and analysis directly from the same polymer surface without the need for sample preparation, high temperature, and pH conditions typically required for in-solution trypsin digestions. Digestion reactions were conducted with 2 μL protein sample droplets (0.35 mM) at incubation temperatures of 4, 25, 37, and 65 °C and digestion reaction times between 2 and 24 h. Sequence coverages were dependent on the hydrophobicity of the OSX polymer support and varied by temperature and digestion time. Under the best conditions, the sequence coverages, determined by DESI-MS, were 100% for melittin, 100% for cytochrome c, 90% for myoglobin, and 65% for bovine serum albumin.
View details for DOI 10.1021/acs.analchem.5b03669
View details for PubMedID 26567450
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Syntheses of Isoquinoline and Substituted Quinolines in Charged Microdroplets
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2015; 54 (49): 14795-14799
Abstract
A Pomeranz-Fritsch synthesis of isoquinoline and Friedländer and Combes syntheses of substituted quinolines were conducted in charged microdroplets produced by an electrospray process at ambient temperature and atmospheric pressure. In the bulk phase, all of these reactions are known to take a long time ranging from several minutes to a few days and to require very high acid concentrations. In sharp contrast, the present report provides clear evidence that all of these reactions occur on the millisecond timescale in the charged microdroplets without the addition of any external acid. Decreasing the droplet size and increasing the charge of the droplet both strongly contribute to reaction rate acceleration, suggesting that the reaction occurs in a confined environment on the charged surface of the droplet.
View details for DOI 10.1002/anie.201507805
View details for Web of Science ID 000367723400033
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Syntheses of Isoquinoline and Substituted Quinolines in Charged Microdroplets.
Angewandte Chemie (International ed. in English)
2015; 54 (49): 14795-14799
Abstract
A Pomeranz-Fritsch synthesis of isoquinoline and Friedländer and Combes syntheses of substituted quinolines were conducted in charged microdroplets produced by an electrospray process at ambient temperature and atmospheric pressure. In the bulk phase, all of these reactions are known to take a long time ranging from several minutes to a few days and to require very high acid concentrations. In sharp contrast, the present report provides clear evidence that all of these reactions occur on the millisecond timescale in the charged microdroplets without the addition of any external acid. Decreasing the droplet size and increasing the charge of the droplet both strongly contribute to reaction rate acceleration, suggesting that the reaction occurs in a confined environment on the charged surface of the droplet.
View details for DOI 10.1002/anie.201507805
View details for PubMedID 26450661
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Mechanistic Insights into Two-Phase Radical C-H Arylations.
ACS central science
2015; 1 (8): 456-462
Abstract
Kinetic, spectroscopic, and computational studies of radical C-H arylations highlight the interplay between chemical and physical rate processes in these multiphase reactions. Anomalous concentration dependences observed here may be reconciled by considering the role of phase transfer processes that mediate concentrations in each phase. In addition, understanding interactions through phase boundaries enables their use in optimization of reaction performance.
View details for PubMedID 26640819
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Mechanistic Insights into Two-Phase Radical C-H Arylations
ACS CENTRAL SCIENCE
2015; 1 (8): 456-462
Abstract
Kinetic, spectroscopic, and computational studies of radical C-H arylations highlight the interplay between chemical and physical rate processes in these multiphase reactions. Anomalous concentration dependences observed here may be reconciled by considering the role of phase transfer processes that mediate concentrations in each phase. In addition, understanding interactions through phase boundaries enables their use in optimization of reaction performance.
View details for DOI 10.1021/acscentsci.5b00332
View details for Web of Science ID 000365969600011
View details for PubMedCentralID PMC4665085
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Imaging of Proteins in Tissue Samples Using Nanospray Desorption Electrospray Ionization Mass Spectrometry
ANALYTICAL CHEMISTRY
2015; 87 (22): 11171-11175
Abstract
Chemical maps of tissue samples provide important information on biological processes therein. Recently, advances in tissue imaging have been achieved using ambient ionization techniques, such as desorption electrospray ionization mass spectrometry (DESI-MS), but such techniques have been almost exclusively confined to the mapping of lipids and metabolites. We report here the use of nanospray desorption electrospray ionization (nanoDESI) that allows us to image proteins in tissue samples in a label-free manner at atmospheric pressure with only minimum sample preparation. Multiply charged proteins with masses up to 15 kDa were successfully detected by nanoDESI using an LTQ Orbitrap mass spectrometer. In an adult mice brain section, expression of proteins including ubiquitin, β-thymosin, myelin basic protein, and hemoglobin were spatially mapped and characterized. We also determined the location of methylation on myelin basic protein. This imaging modality was further implemented to MYC-induced lymphomas. We observed an array of truncated proteins in the region where normal thymus cells were infiltrated by tumor cells, in contrast to healthy tissue.
View details for DOI 10.1021/acs.analchem.5b03389
View details for PubMedID 26509582
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Acceleration of reaction in charged microdroplets
QUARTERLY REVIEWS OF BIOPHYSICS
2015; 48 (4): 437-444
Abstract
Using high-resolution mass spectrometry, we have studied the synthesis of isoquinoline in a charged electrospray droplet and the complexation between cytochrome c and maltose in a fused droplet to investigate the feasibility of droplets to drive reactions (both covalent and noncovalent interactions) at a faster rate than that observed in conventional bulk solution. In both the cases we found marked acceleration of reaction, by a factor of a million or more in the former and a factor of a thousand or more in the latter. We believe that carrying out reactions in microdroplets (about 1-15 μm in diameter corresponding to 0·5 pl - 2 nl) is a general method for increasing reaction rates. The mechanism is not presently established but droplet evaporation and droplet confinement of reagents appear to be two important factors among others. In the case of fused water droplets, evaporation has been shown to be almost negligible during the flight time from where droplet fusion occurs and the droplets enter the heated capillary inlet of the mass spectrometer. This suggests that (1) evaporation is not responsible for the acceleration process in aqueous droplet fusion and (2) the droplet-air interface may play a significant role in accelerating the reaction. We argue that this 'microdroplet chemistry' could be a remarkable alternative to accelerate slow and difficult reactions, and in conjunction with mass spectrometry, it may provide a new arena to study chemical and biochemical reactions in a confined environment.
View details for DOI 10.1017/S0033583515000086
View details for Web of Science ID 000364764300008
View details for PubMedID 26537403
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Catalytic Role of Multinuclear Palladium-Oxygen Intermediates in Aerobic Oxidation Followed by Hydrogen Peroxide Disproportionation
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2015; 137 (42): 13632-13646
Abstract
Aerobic oxidation of alcohols are catalyzed by the Pd-acetate compound [LPd(OAc)]2(OTf)2 (L = neocuproine = 2,9-dimethyl-1,10-phenanthroline) to form ketones and the release of hydrogen peroxide, but the latter rapidly undergoes disproportionation. We employ a series of kinetic and isotope labeling studies made largely possible by electrospray ionization mass spectrometry to determine the role of intermediates in causing this complex chemical transformation. The data suggested that multiple catalytic paths for H2O2 disproportionation occur, which involve formation and consumption of multinuclear Pd species. We find that the trinuclear compound [(LPd)3(μ(3)-O)2](2+), which we have identified in a previous study, is a product of dioxygen activation that is formed during aerobic oxidations of alcohols catalyzed by [LPd(OAc)]2(OTf)2. It is also a product of hydrogen peroxide activation during disproportionation reactions catalyzed by [LPd(OAc)]2(OTf)2. The results suggest that this trinuclear Pd compound is involved in one of the simultaneous mechanisms for the reduction of oxygen and/or the disproportionation of hydrogen peroxide during oxidation catalysis. Electrospray ionization mass spectrometry of hydrogen peroxide disproportionation reactions suggested the presence of other multinuclear Pd-O2 species in solution. Theoretical calculations of these compounds yield some insight into their structure and potential chemistry.
View details for DOI 10.1021/jacs.5b08719
View details for Web of Science ID 000363916600031
View details for PubMedID 26444100
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Challenges of metagenomics and single-cell genomics approaches for exploring cyanobacterial diversity.
Photosynthesis research
2015; 126 (1): 135-146
Abstract
Cyanobacteria have played a crucial role in the history of early earth and continue to be instrumental in shaping our planet, yet applications of cutting edge technology have not yet been widely used to explore cyanobacterial diversity. To provide adequate background, we briefly review current sequencing technologies and their innovative uses in genomics and metagenomics. Next, we focus on current cell capture technologies and the challenges of using them with cyanobacteria. We illustrate the utility in coupling breakthroughs in DNA amplification with cell capture platforms, with an example of microfluidic isolation and subsequent targeted amplicon sequencing from individual terrestrial thermophilic cyanobacteria. Single cells of thermophilic, unicellular Synechococcus sp. JA-2-3-B'a(2-13) (Syn OS-B') were sorted in a microfluidic device, lysed, and subjected to whole genome amplification by multiple displacement amplification. We amplified regions from specific CRISPR spacer arrays, which are known to be highly diverse, contain semi-palindromic repeats which form secondary structure, and can be difficult to amplify. Cell capture, lysis, and genome amplification on a microfluidic device have been optimized, setting a stage for further investigations of individual cyanobacterial cells isolated directly from natural populations.
View details for DOI 10.1007/s11120-014-0066-9
View details for PubMedID 25515769
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Celecoxib Nanoparticles for Therapeutic Angiogenesis.
ACS nano
2015; 9 (9): 9416-9426
Abstract
Controllable induction of blood vessel formation (angiogenesis) presents an important therapeutic goal in ischemic diseases and is also beneficial in various normal physiological processes. In this study, we have shown that nanoparticles of celecoxib, a lipophilic nonsteroidal anti-inflammatory drug, effectively evoke therapeutic angiogenesis in animal models, in both normal and ischemic organs. Celecoxib is widely considered to inhibit angiogenesis, although a recent study suggests that it can instead promote blood vessel growth in cancer cell lines. The hydrophobic nature of this drug necessitates its administration in nanoparticulate form in order to elicit a perceivable pharmacological response. We developed a facile method for nanoparticle formation by solvent extraction from microemulsions in supercritical carbon dioxide. This method exploits a spontaneous formation of nanometric domains within the microemulsion system and their rapid conversion to nanoparticles by supercritical fluid. The resultant nanoparticles were administered subcutaneously to mice in a biocompatible hydrogel, and caused a 4-fold increase in blood vessel count in normally perfused skin compared with drug-free particles. They were at least as effective in inducing angiogenesis as nanoparticles of deferoxamine, a well-established neovascularization promoter. Next, we evaluated their effect on ischemic tissues in murine model of myocardial infarction. We found that celecoxib nanoparticles were able to induce a significant vascularization of ischemic myocardium and hamper the progression of heart failure, which points toward a new approach for treating ischemia.
View details for DOI 10.1021/acsnano.5b04137
View details for PubMedID 26244654
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Detection of the Short-Lived Radical Cation Intermediate in the Electrooxidation of N,N-Dimethylaniline by Mass Spectrometry.
Angewandte Chemie (International ed. in English)
2015; 54 (38): 11183-11185
Abstract
The N,N-dimethylaniline (DMA) radical cation DMA(.+) , a long-sought transient intermediate, was detected by mass spectrometry (MS) during the electrochemical oxidation of DMA. This was accomplished by coupling desorption electrospray ionization (DESI) MS with a waterwheel working electrode setup to sample the surface of the working electrode during electrochemical analysis. This study clearly shows that DESI-based electrochemical MS is capable of capturing electrochemically generated intermediates with half-lives on the order of microseconds, which is 4-5 orders of magnitude faster than previously reported electrochemical mass spectrometry techniques.
View details for DOI 10.1002/anie.201506316
View details for PubMedID 26352029
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Droplet Spray Ionization from a Glass Microscope Slide: Real-Time Monitoring of Ethylene Polymerization
ANALYTICAL CHEMISTRY
2015; 87 (16): 8057-8062
Abstract
Ambient ionization mass spectrometry is achieved in a simple manner by loading a sample solution onto a corner of a microscope cover glass positioned in front of the inlet to a mass spectrometer and applying a high voltage to the sample. The resulting stream of charged droplets is stable, has no contamination from the substrate platform, and can be used repeatedly. The utility of droplet spray for in situ analysis and real-time monitoring of chemical reactions was demonstrated by the bis(cyclopentadienyl)zirconium dichloride (zirconocene dichloride)/methylaluminoxane, Cp2ZrCl2/MAO, homogeneously catalyzed polymerization of ethylene in various solutions. Reaction times ranged from seconds to minutes, and catalytically active species and polymeric products of ethylene were acquired and identified by tandem mass spectrometry.
View details for DOI 10.1021/acs.analchem.5b02390
View details for Web of Science ID 000359892100005
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Droplet spray ionization from a glass microscope slide: real-time monitoring of ethylene polymerization.
Analytical chemistry
2015; 87 (16): 8057-62
Abstract
Ambient ionization mass spectrometry is achieved in a simple manner by loading a sample solution onto a corner of a microscope cover glass positioned in front of the inlet to a mass spectrometer and applying a high voltage to the sample. The resulting stream of charged droplets is stable, has no contamination from the substrate platform, and can be used repeatedly. The utility of droplet spray for in situ analysis and real-time monitoring of chemical reactions was demonstrated by the bis(cyclopentadienyl)zirconium dichloride (zirconocene dichloride)/methylaluminoxane, Cp2ZrCl2/MAO, homogeneously catalyzed polymerization of ethylene in various solutions. Reaction times ranged from seconds to minutes, and catalytically active species and polymeric products of ethylene were acquired and identified by tandem mass spectrometry.
View details for DOI 10.1021/acs.analchem.5b02390
View details for PubMedID 26204485
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Multinuclear palladium oxygen species related to aerobic oxidation catalysis
AMER CHEMICAL SOC. 2015
View details for Web of Science ID 000432475700362
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Quantum interference between H + D-2 quasiclassical reaction mechanisms
NATURE CHEMISTRY
2015; 7 (8): 661-667
Abstract
Interferences are genuine quantum phenomena that appear whenever two seemingly distinct classical trajectories lead to the same outcome. They are common in elastic scattering but are seldom observable in chemical reactions. Here we report experimental measurements of the state-to-state angular distribution for the H + D2 reaction using the 'photoloc' technique. For products in low rotational and vibrational states, a characteristic oscillation pattern governs backward scattering. The comparison between the experiments, rigorous quantum calculations and classical trajectories on an accurate potential energy surface allows us to trace the origin of that structure to the quantum interference between different quasiclassical mechanisms, a phenomenon analogous to that observed in the double-slit experiment.
View details for DOI 10.1038/NCHEM.2295
View details for Web of Science ID 000358529600012
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Quantum interference between H + D2 quasiclassical reaction mechanisms.
Nature chemistry
2015; 7 (8): 661-7
Abstract
Interferences are genuine quantum phenomena that appear whenever two seemingly distinct classical trajectories lead to the same outcome. They are common in elastic scattering but are seldom observable in chemical reactions. Here we report experimental measurements of the state-to-state angular distribution for the H + D2 reaction using the 'photoloc' technique. For products in low rotational and vibrational states, a characteristic oscillation pattern governs backward scattering. The comparison between the experiments, rigorous quantum calculations and classical trajectories on an accurate potential energy surface allows us to trace the origin of that structure to the quantum interference between different quasiclassical mechanisms, a phenomenon analogous to that observed in the double-slit experiment.
View details for DOI 10.1038/nchem.2295
View details for PubMedID 26201743
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Identification of Fleeting Electrochemical Reaction Intermediates Using Desorption Electrospray Ionization Mass Spectrometry.
Journal of the American Chemical Society
2015; 137 (23): 7274-7277
Abstract
We report a new method for the mass spectrometric detection of fleeting reaction intermediates in electrochemical reactions utilizing a "waterwheel" working electrode setup. This setup takes inspiration from desorption electrospray ionization (DESI) mass spectrometry, where the sampling time is on the order of milliseconds, to sample directly from the surface of a working electrode for mass spectrometric analysis. We present data that show the formation of a diimine intermediate of the electrochemical oxidation of uric acid that has a lifetime in solution of 23 ms as well as data that provide evidence for the formation of a similar diimine species from the electrooxidation of xanthine, which has not been previously observed.
View details for DOI 10.1021/jacs.5b03862
View details for PubMedID 26030136
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MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2015; 112 (21): 6539-6544
Abstract
The MYC oncogene is frequently mutated and overexpressed in human renal cell carcinoma (RCC). However, there have been no studies on the causative role of MYC or any other oncogene in the initiation or maintenance of kidney tumorigenesis. Here, we show through a conditional transgenic mouse model that the MYC oncogene, but not the RAS oncogene, initiates and maintains RCC. Desorption electrospray ionization-mass-spectrometric imaging was used to obtain chemical maps of metabolites and lipids in the mouse RCC samples. Gene expression analysis revealed that the mouse tumors mimicked human RCC. The data suggested that MYC-induced RCC up-regulated the glutaminolytic pathway instead of the glycolytic pathway. The pharmacologic inhibition of glutamine metabolism with bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide impeded MYC-mediated RCC tumor progression. Our studies demonstrate that MYC overexpression causes RCC and points to the inhibition of glutamine metabolism as a potential therapeutic approach for the treatment of this disease.
View details for DOI 10.1073/pnas.1507228112
View details for PubMedID 25964345
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Laser-Based Mass Spectrometric Assessment of Asphaltene Molecular Weight, Molecular Architecture, and Nanoaggregate Number
ENERGY & FUELS
2015; 29 (5): 2833-2842
View details for DOI 10.1021/ef5020764
View details for Web of Science ID 000355158200011
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Microdroplet fusion mass spectrometry for fast reaction kinetics
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2015; 112 (13): 3898-3903
Abstract
We investigated the fusion of high-speed liquid droplets as a way to record the kinetics of liquid-phase chemical reactions on the order of microseconds. Two streams of micrometer-size droplets collide with one another. The droplets that fused (13 μm in diameter) at the intersection of the two streams entered the heated capillary inlet of a mass spectrometer. The mass spectrum was recorded as a function of the distance x between the mass spectrometer inlet and the droplet fusion center. Fused droplet trajectories were imaged with a high-speed camera, revealing that the droplet fusion occurred approximately within a 500-μm radius from the droplet fusion center and both the size and the speed of the fused droplets remained relatively constant as they traveled from the droplet fusion center to the mass spectrometer inlet. Evidence is presented that the reaction effectively stops upon entering the heated inlet of the mass spectrometer. Thus, the reaction time was proportional to x and could be measured and manipulated by controlling the distance x. Kinetic studies were carried out in fused water droplets for acid-induced unfolding of cytochrome c and hydrogen-deuterium exchange in bradykinin. The kinetics of the former revealed the slowing of the unfolding rates at the early stage of the reaction within 50 μs. The hydrogen-deuterium exchange revealed the existence of two distinct populations with fast and slow exchange rates. These studies demonstrated the power of this technique to detect reaction intermediates in fused liquid droplets with microsecond temporal resolution.
View details for DOI 10.1073/pnas.1503689112
View details for Web of Science ID 000351914500040
View details for PubMedID 25775573
View details for PubMedCentralID PMC4386409
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Incorporating peer-review homework assignments into a large enrollment freshman chemistry course
AMER CHEMICAL SOC. 2015
View details for Web of Science ID 000411183303135
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Mechanistic analysis of an asymmetric palladium-catalyzed conjugate addition of arylboronic acids to β-substituted cyclic enones.
Chemical science
2015; 6 (3): 1917-1922
Abstract
An asymmetric palladium-catalyzed conjugate addition reaction of arylboronic acids to enone substrates was investigated mechanistically. Desorption electrospray ionization coupled to mass spectrometry was used to identify intermediates of the catalytic cycle and delineate differences in substrate reactivity. Our findings provide evidence for the catalytic cycle proceeding through formation of an arylpalladium(II) cation, subsequent formation of an arylpalladium-enone complex, and, ultimately, formation of the new C-C bond. Reaction monitoring in both positive and negative ion modes revealed that 4-iodophenylboronic acid formed a relatively stable trimeric species under the reaction conditions.
View details for DOI 10.1039/C4SC03337J
View details for PubMedID 25729560
View details for PubMedCentralID PMC4338963
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The role of Abcb5 alleles in susceptibility to haloperidol-induced toxicity in mice and humans.
PLoS medicine
2015; 12 (2)
Abstract
We know very little about the genetic factors affecting susceptibility to drug-induced central nervous system (CNS) toxicities, and this has limited our ability to optimally utilize existing drugs or to develop new drugs for CNS disorders. For example, haloperidol is a potent dopamine antagonist that is used to treat psychotic disorders, but 50% of treated patients develop characteristic extrapyramidal symptoms caused by haloperidol-induced toxicity (HIT), which limits its clinical utility. We do not have any information about the genetic factors affecting this drug-induced toxicity. HIT in humans is directly mirrored in a murine genetic model, where inbred mouse strains are differentially susceptible to HIT. Therefore, we genetically analyzed this murine model and performed a translational human genetic association study.A whole genome SNP database and computational genetic mapping were used to analyze the murine genetic model of HIT. Guided by the mouse genetic analysis, we demonstrate that genetic variation within an ABC-drug efflux transporter (Abcb5) affected susceptibility to HIT. In situ hybridization results reveal that Abcb5 is expressed in brain capillaries, and by cerebellar Purkinje cells. We also analyzed chromosome substitution strains, imaged haloperidol abundance in brain tissue sections and directly measured haloperidol (and its metabolite) levels in brain, and characterized Abcb5 knockout mice. Our results demonstrate that Abcb5 is part of the blood-brain barrier; it affects susceptibility to HIT by altering the brain concentration of haloperidol. Moreover, a genetic association study in a haloperidol-treated human cohort indicates that human ABCB5 alleles had a time-dependent effect on susceptibility to individual and combined measures of HIT. Abcb5 alleles are pharmacogenetic factors that affect susceptibility to HIT, but it is likely that additional pharmacogenetic susceptibility factors will be discovered.ABCB5 alleles alter susceptibility to HIT in mouse and humans. This discovery leads to a new model that (at least in part) explains inter-individual differences in susceptibility to a drug-induced CNS toxicity.
View details for DOI 10.1371/journal.pmed.1001782
View details for PubMedID 25647612
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The role of abcb5 alleles in susceptibility to haloperidol-induced toxicity in mice and humans.
PLoS medicine
2015; 12 (2): e1001782
Abstract
We know very little about the genetic factors affecting susceptibility to drug-induced central nervous system (CNS) toxicities, and this has limited our ability to optimally utilize existing drugs or to develop new drugs for CNS disorders. For example, haloperidol is a potent dopamine antagonist that is used to treat psychotic disorders, but 50% of treated patients develop characteristic extrapyramidal symptoms caused by haloperidol-induced toxicity (HIT), which limits its clinical utility. We do not have any information about the genetic factors affecting this drug-induced toxicity. HIT in humans is directly mirrored in a murine genetic model, where inbred mouse strains are differentially susceptible to HIT. Therefore, we genetically analyzed this murine model and performed a translational human genetic association study.A whole genome SNP database and computational genetic mapping were used to analyze the murine genetic model of HIT. Guided by the mouse genetic analysis, we demonstrate that genetic variation within an ABC-drug efflux transporter (Abcb5) affected susceptibility to HIT. In situ hybridization results reveal that Abcb5 is expressed in brain capillaries, and by cerebellar Purkinje cells. We also analyzed chromosome substitution strains, imaged haloperidol abundance in brain tissue sections and directly measured haloperidol (and its metabolite) levels in brain, and characterized Abcb5 knockout mice. Our results demonstrate that Abcb5 is part of the blood-brain barrier; it affects susceptibility to HIT by altering the brain concentration of haloperidol. Moreover, a genetic association study in a haloperidol-treated human cohort indicates that human ABCB5 alleles had a time-dependent effect on susceptibility to individual and combined measures of HIT. Abcb5 alleles are pharmacogenetic factors that affect susceptibility to HIT, but it is likely that additional pharmacogenetic susceptibility factors will be discovered.ABCB5 alleles alter susceptibility to HIT in mouse and humans. This discovery leads to a new model that (at least in part) explains inter-individual differences in susceptibility to a drug-induced CNS toxicity.
View details for DOI 10.1371/journal.pmed.1001782
View details for PubMedID 25647612
View details for PubMedCentralID PMC4315575
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Transforming plastic surfaces with electrophilic backbones from hydrophobic to hydrophilic.
ACS applied materials & interfaces
2015; 7 (3): 1925-1931
Abstract
We demonstrate a simple nonaqueous reaction scheme for transforming the surface of plastics from hydrophobic to hydrophilic. The chemical modification is achieved by base-catalyzed trans-esterification with polyols. It is permanent, does not release contaminants, and causes no optical or mechanical distortion of the plastic. We present contact angle measurements to show successful modification of several types of plastics including poly(ethylene terephthalate) (PET) and polycarbonate (PC). Its applicability to blood analysis is explored using chemically modified PET blood collection tubes and found to be quite satisfactory. We expect this approach will reduce the cost of manufacturing plastic devices with optimized wettability and can be generalized to other types of plastic materials having an electrophilic linkage as its backbone.
View details for DOI 10.1021/am507606r
View details for PubMedID 25565370
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Rapid and selective detection of viruses using virus-imprinted polymer films
NANOSCALE
2015; 7 (45): 18998-19003
View details for DOI 10.1039/c5nr06114h
View details for PubMedID 26513039
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Carl Djerassi (1923-2015).
Angewandte Chemie (International ed. in English)
2015; 54 (17): 5001–2
View details for PubMedID 25809781
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Miniaturized Antimicrobial Susceptibility Test by Combining Concentration Gradient Generation and Rapid Cell Culturing.
Antibiotics (Basel, Switzerland)
2015; 4 (4): 455-466
Abstract
Effective treatment of bacterial infection relies on timely diagnosis and proper prescription of antibiotic drugs. The antimicrobial susceptibility test (AST) is one of the most crucial experimental procedures, providing the baseline information for choosing effective antibiotic agents and their dosages. Conventional methods, however, require long incubation times or significant instrumentation costs to obtain test results. We propose a lab-on-a-chip approach to perform AST in a simple, economic, and rapid manner. Our assay platform miniaturizes the standard broth microdilution method on a microfluidic device (20 × 20 mm) that generates an antibiotic concentration gradient and delivers antibiotic-containing culture media to eight 30-nL chambers for cell culture. When tested with 20 μL samples of a model bacterial strain (E. coli ATCC 25922) treated with ampicillin or streptomycin, our method allows for the determination of minimum inhibitory concentrations consistent with the microdilution test in three hours, which is almost a factor of ten more rapid than the standard method.
View details for DOI 10.3390/antibiotics4040455
View details for PubMedID 27025635
View details for PubMedCentralID PMC4790307
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Polypyrrole nanoparticles for tunable, pH-sensitive and sustained drug release
NANOSCALE
2015; 7 (21): 9497-9504
Abstract
We report the development of a generalized pH-sensitive drug delivery system that can release any charged drug preferentially at the pH range of interest. Our system is based on polypyrrole nanoparticles (PPy NPs), synthesized via a simple one-step microemulsion technique. These nanoparticles are highly monodisperse, stable in solution over the period of a month, and have good drug loading capacity (∼15 wt%). We show that PPy NPs can be tuned to release drugs at both acidic and basic pH by varying the pH, the charge of the drug, as well as by adding small amounts of charged amphiphiles. Moreover, these NPs may be delivered locally by immobilizing them in a hydrogel. Our studies show encapsulation within a calcium alginate hydrogel results in sustained release of the incorporated drug for more than 21 days. Such a nanoparticle-hydrogel composite drug delivery system is promising for treatment of long-lasting conditions such as cancer and chronic pain which require controlled, localized, and sustained drug release.
View details for DOI 10.1039/c5nr02196k
View details for Web of Science ID 000354983100021
View details for PubMedID 25931037
- Acceleration of Reaction in Charged Microdroplets Quarterly Reviews of Biophysics 2015
- Laser-Based Mass Spectrometric Assessment of Asphaltene Molecular Weight, Molecular Architecture and Nanoaggregate Number Energy & Fuels 2015
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Microdroplet fusion mass spectrometry for fast reaction kinetics
Proceedings of the National Academy of Sciences of the United States of America
2015
View details for DOI 10.1073/pnas 1503689112
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Laser desorption lamp ionization source for ion trap mass spectrometry
JOURNAL OF MASS SPECTROMETRY
2015; 50 (1): 160-164
Abstract
A two-step laser desorption lamp ionization source coupled to an ion trap mass spectrometer (LDLI-ITMS) has been constructed and characterized. The pulsed infrared (IR) output of an Nd:YAG laser (1064 nm) is directed to a target inside a chamber evacuated to ~15 Pa causing desorption of molecules from the target's surface. The desorbed molecules are ionized by a vacuum ultraviolet (VUV) lamp (filled with xenon, major wavelength at 148 nm). The resulting ions are stored and detected in a three-dimensional quadrupole ion trap modified from a Finnigan Mat LCQ mass spectrometer operated at a pressure of ≥ 0.004 Pa. The limit of detection for desorbed coronene molecules is 1.5 pmol, which is about two orders of magnitude more sensitive than laser desorption laser ionization mass spectrometry using a fluorine excimer laser (157 nm) as the ionization source. The mass spectrum of four standard aromatic compounds (pyrene, coronene, rubrene and 1,4,8,11,15,18,22,25-octabutoxy-29H,31H-phthalocyanine (OPC)) shows that parent ions dominate. By increasing the infrared laser power, this instrument is capable of detecting inorganic compounds.
View details for DOI 10.1002/jms.3509
View details for Web of Science ID 000348721800022
View details for PubMedID 25601688
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Mechanistic analysis of an asymmetric palladium-catalyzed conjugate addition of arylboronic acids to beta-substituted cyclic enones
CHEMICAL SCIENCE
2015; 6 (3): 1917-1922
Abstract
An asymmetric palladium-catalyzed conjugate addition reaction of arylboronic acids to enone substrates was investigated mechanistically. Desorption electrospray ionization coupled to mass spectrometry was used to identify intermediates of the catalytic cycle and delineate differences in substrate reactivity. Our findings provide evidence for the catalytic cycle proceeding through formation of an arylpalladium(II) cation, subsequent formation of an arylpalladium-enone complex, and, ultimately, formation of the new C-C bond. Reaction monitoring in both positive and negative ion modes revealed that 4-iodophenylboronic acid formed a relatively stable trimeric species under the reaction conditions.
View details for DOI 10.1039/c4sc03337j
View details for Web of Science ID 000349832600037
View details for PubMedCentralID PMC4338963
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One-Pot Synthesis of Protein-Embedded Metal-Organic Frameworks with Enhanced Biological Activities
NANO LETTERS
2014; 14 (10): 5761-5765
Abstract
Protein molecules were directly embedded in metal-organic frameworks (MOFs) by a coprecipitation method. The protein molecules majorly embedded on the surface region of MOFs display high biological activities. As a demonstration of the power of such materials, the resulting Cyt c embedded in ZIF-8 showed a 10-fold increase in peroxidase activity compared to free Cyt c in solution and thus gave convenient, fast, and highly sensitive detection of trace amounts of explosive organic peroxides in solution.
View details for DOI 10.1021/nl5026419
View details for Web of Science ID 000343016400044
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Diamondosomes: Submicron Colloidosomes with Nanodiamond Shells
PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION
2014; 31 (10): 1067-1071
View details for DOI 10.1002/ppsc.201400022
View details for Web of Science ID 000343878000004
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LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis
PLOS PATHOGENS
2014; 10 (9)
Abstract
Mycobacterium tuberculosis employs various virulence strategies to subvert host immune responses in order to persist and cause disease. Interaction of M. tuberculosis with mannose receptor on macrophages via surface-exposed lipoarabinomannan (LAM) is believed to be critical for cell entry, inhibition of phagosome-lysosome fusion, and intracellular survival, but in vivo evidence is lacking. LprG, a cell envelope lipoprotein that is essential for virulence of M. tuberculosis, has been shown to bind to the acyl groups of lipoglycans but the role of LprG in LAM biosynthesis and localization remains unknown. Using an M. tuberculosis lprG mutant, we show that LprG is essential for normal surface expression of LAM and virulence of M. tuberculosis attributed to LAM. The lprG mutant had a normal quantity of LAM in the cell envelope, but its surface was altered and showed reduced expression of surface-exposed LAM. Functionally, the lprG mutant was defective for macrophage entry and inhibition of phagosome-lysosome fusion, was attenuated in macrophages, and was killed in the mouse lung with the onset of adaptive immunity. This study identifies the role of LprG in surface-exposed LAM expression and provides in vivo evidence for the essential role surface LAM plays in M. tuberculosis virulence. Findings have translational implications for therapy and vaccine development.
View details for DOI 10.1371/journal.ppat.1004376
View details for Web of Science ID 000343014600035
View details for PubMedCentralID PMC4169494
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LprG-mediated surface expression of lipoarabinomannan is essential for virulence of Mycobacterium tuberculosis.
PLoS pathogens
2014; 10 (9)
Abstract
Mycobacterium tuberculosis employs various virulence strategies to subvert host immune responses in order to persist and cause disease. Interaction of M. tuberculosis with mannose receptor on macrophages via surface-exposed lipoarabinomannan (LAM) is believed to be critical for cell entry, inhibition of phagosome-lysosome fusion, and intracellular survival, but in vivo evidence is lacking. LprG, a cell envelope lipoprotein that is essential for virulence of M. tuberculosis, has been shown to bind to the acyl groups of lipoglycans but the role of LprG in LAM biosynthesis and localization remains unknown. Using an M. tuberculosis lprG mutant, we show that LprG is essential for normal surface expression of LAM and virulence of M. tuberculosis attributed to LAM. The lprG mutant had a normal quantity of LAM in the cell envelope, but its surface was altered and showed reduced expression of surface-exposed LAM. Functionally, the lprG mutant was defective for macrophage entry and inhibition of phagosome-lysosome fusion, was attenuated in macrophages, and was killed in the mouse lung with the onset of adaptive immunity. This study identifies the role of LprG in surface-exposed LAM expression and provides in vivo evidence for the essential role surface LAM plays in M. tuberculosis virulence. Findings have translational implications for therapy and vaccine development.
View details for DOI 10.1371/journal.ppat.1004376
View details for PubMedID 25232742
View details for PubMedCentralID PMC4169494
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Chemical modification of plastic blood collection tubes to achieve hydrophilic interior surfaces
AMER CHEMICAL SOC. 2014
View details for Web of Science ID 000349165101632
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Reaction dynamics in liquid droplets
AMER CHEMICAL SOC. 2014
View details for Web of Science ID 000349167404100
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Ambient ionization mass spectrometric imaging with high spatiotemporal resolution
AMER CHEMICAL SOC. 2014
View details for Web of Science ID 000349165101524
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Power of a lecture demonstration
AMER CHEMICAL SOC. 2014
View details for Web of Science ID 000349165102808
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Trinuclear Pd3O2 intermediate in aerobic oxidation catalysis
AMER CHEMICAL SOC. 2014
View details for Web of Science ID 000349167401672
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Fall, recovery, and characterization of the Novato L6 chondrite breccia
METEORITICS & PLANETARY SCIENCE
2014; 49 (8): 1388-1425
View details for DOI 10.1111/maps.12323
View details for Web of Science ID 000340875900007
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Alteration of the lipid profile in lymphomas induced by MYC overexpression.
Proceedings of the National Academy of Sciences of the United States of America
2014; 111 (29): 10450-10455
Abstract
Overexpression of the v-myc avian myelocytomatosis viral oncogene homolog (MYC) oncogene is one of the most commonly implicated causes of human tumorigenesis. MYC is known to regulate many aspects of cellular biology including glucose and glutamine metabolism. Little is known about the relationship between MYC and the appearance and disappearance of specific lipid species. We use desorption electrospray ionization mass spectrometry imaging (DESI-MSI), statistical analysis, and conditional transgenic animal models and cell samples to investigate changes in lipid profiles in MYC-induced lymphoma. We have detected a lipid signature distinct from that observed in normal tissue and in rat sarcoma-induced lymphoma cells. We found 104 distinct molecular ions that have an altered abundance in MYC lymphoma compared with normal control tissue by statistical analysis with a false discovery rate of less than 5%. Of these, 86 molecular ions were specifically identified as complex phospholipids. To evaluate whether the lipid signature could also be observed in human tissue, we examined 15 human lymphoma samples with varying expression levels of MYC oncoprotein. Distinct lipid profiles in lymphomas with high and low MYC expression were observed, including many of the lipid species identified as significant for MYC-induced animal lymphoma tissue. Our results suggest a relationship between the appearance of specific lipid species and the overexpression of MYC in lymphomas.
View details for DOI 10.1073/pnas.1409778111
View details for PubMedID 24994904
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Bactericidal Activity of Partially Oxidized Nanodiamonds
ACS NANO
2014; 8 (6): 6475-6483
Abstract
Nanodiamonds are a class of carbon-based nanoparticles that are rapidly gaining attention, particularly for biomedical applications, i.e., as drug carriers, for bioimaging, or as implant coatings. Nanodiamonds have generally been considered biocompatible with a broad variety of eukaryotic cells. We show that, depending on their surface composition, nanodiamonds kill Gram-positive and -negative bacteria rapidly and efficiently. We investigated six different types of nanodiamonds exhibiting diverse oxygen-containing surface groups that were created using standard pretreatment methods for forming nanodiamond dispersions. Our experiments suggest that the antibacterial activity of nanodiamond is linked to the presence of partially oxidized and negatively charged surfaces, specifically those containing acid anhydride groups. Furthermore, proteins were found to control the bactericidal properties of nanodiamonds by covering these surface groups, which explains the previously reported biocompatibility of nanodiamonds. Our findings describe the discovery of an exciting property of partially oxidized nanodiamonds as a potent antibacterial agent.
View details for DOI 10.1021/nn502230m
View details for Web of Science ID 000338089200117
View details for PubMedID 24861876
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Trinuclear pd3 o2 intermediate in aerobic oxidation catalysis.
Angewandte Chemie (International ed. in English)
2014; 53 (22): 5648-5652
Abstract
The activation of O2 is a key step in selective catalytic aerobic oxidation reactions mediated by transition metals. The bridging trinuclear palladium species, [(LPd(II))3(μ(3)-O)2](2+) (L=2,9-dimethylphenanthroline), was identified during the [LPd(OAc)]2(OTf)2-catalyzed aerobic oxidation of 1,2-propanediol. Independent synthesis, structural characterization, and catalytic studies of the trinuclear compound show that it is a product of oxygen activation by reduced palladium species and is a competent intermediate in the catalytic aerobic oxidation of alcohols. The formation and catalytic activity of the trinuclear Pd3O2 species illuminates a multinuclear pathway for aerobic oxidation reactions catalyzed by Pd complexes.
View details for DOI 10.1002/anie.201400134
View details for PubMedID 24711099
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Scientific Authorship: Giving Credit Where Credit Is Due
CURRENT SCIENCE
2014; 106 (9): 1171-1172
View details for Web of Science ID 000336354900001
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Constant Asphaltene Molecular and Nanoaggregate Mass in a Gravitationally Segregated Reservoir
ENERGY & FUELS
2014; 28 (5): 3010-3015
View details for DOI 10.1021/ef500281s
View details for Web of Science ID 000336199300017
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Visualizing Dermal Permeation of Sodium Channel Modulators by Mass Spectrometric Imaging
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2014; 136 (17): 6401-6405
Abstract
Determining permeability of a given compound through human skin is a principal challenge owing to the highly complex nature of dermal tissue. We describe the application of an ambient mass spectrometry imaging method for visualizing skin penetration of sodium channel modulators, including novel synthetic analogs of natural neurotoxic alkaloids, topically applied ex vivo to human skin. Our simple and label-free approach enables successful mapping of the transverse and lateral diffusion of small molecules having different physicochemical properties without the need for extensive sample preparation.
View details for DOI 10.1021/ja501635u
View details for Web of Science ID 000335369200044
View details for PubMedID 24708172
View details for PubMedCentralID PMC4017602
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Coherent superposition of M-states in a single rovibrational level of H2 by Stark-induced adiabatic Raman passage.
journal of chemical physics
2014; 140 (7): 074201-?
Abstract
We prepare an ensemble of isolated rovibrationally excited (v = 1, J = 2) H2 molecules in a phase-locked superposition of magnetic sublevels M using Stark-induced adiabatic Raman passage with linearly polarized single-mode pump (at 532 nm, ∼6 ns pulse duration, 200 mJ/pulse) and Stokes (699 nm, ∼4 ns pulse duration, 20 mJ/pulse) laser excitation. A biaxial superposition state, given by [Formula: see text], is prepared with linearly but cross-polarized pump and Stokes laser pulses copropagating along the quantization z-axis. The degree of phase coherence is measured by using the O(2) line of the H2 E,F-X (0,1) band via 2 + 1 resonance enhanced multiphoton ionization (REMPI) at 210.8 nm by recording interference fringes in the REMPI signal in a time-of-flight mass spectrometer as the direction of the UV laser polarization is rotated using a half-wave plate. Nearly 60% population transfer from H2 (v = 0, J = 0) ground state to the superposition state in H2 (v = 1, J = 2) is measured from the depletion of the Q(0) line of the E,F-X (0,0) band as the Stokes frequency is tuned across the (v = 0, J = 0) → (v = 1, J = 2) Raman resonance.
View details for DOI 10.1063/1.4865131
View details for PubMedID 24559344
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Molecular assessment of surgical-resection margins of gastric cancer by mass-spectrometric imaging.
Proceedings of the National Academy of Sciences of the United States of America
2014; 111 (7): 2436-2441
Abstract
Surgical resection is the main curative option for gastrointestinal cancers. The extent of cancer resection is commonly assessed during surgery by pathologic evaluation of (frozen sections of) the tissue at the resected specimen margin(s) to verify whether cancer is present. We compare this method to an alternative procedure, desorption electrospray ionization mass spectrometric imaging (DESI-MSI), for 62 banked human cancerous and normal gastric-tissue samples. In DESI-MSI, microdroplets strike the tissue sample, the resulting splash enters a mass spectrometer, and a statistical analysis, here, the Lasso method (which stands for least absolute shrinkage and selection operator and which is a multiclass logistic regression with L1 penalty), is applied to classify tissues based on the molecular information obtained directly from DESI-MSI. The methodology developed with 28 frozen training samples of clear histopathologic diagnosis showed an overall accuracy value of 98% for the 12,480 pixels evaluated in cross-validation (CV), and 97% when a completely independent set of samples was tested. By applying an additional spatial smoothing technique, the accuracy for both CV and the independent set of samples was 99% compared with histological diagnoses. To test our method for clinical use, we applied it to a total of 21 tissue-margin samples prospectively obtained from nine gastric-cancer patients. The results obtained suggest that DESI-MSI/Lasso may be valuable for routine intraoperative assessment of the specimen margins during gastric-cancer surgery.
View details for DOI 10.1073/pnas.1400274111
View details for PubMedID 24550265
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Why Some Pool Shots are More Difficult Than Others
RESONANCE-JOURNAL OF SCIENCE EDUCATION
2014; 19 (2): 114-120
View details for Web of Science ID 000421671100003
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Sorting Bacterium Cells Using Cell-Imprinted Polymer Thin Films: From Concept to Applications
CELL PRESS. 2014: 245A
View details for DOI 10.1016/j.bpj.2013.11.1437
View details for Web of Science ID 000337000401358
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High Resolution Mass Spectrometric Imaging for Single Cell Metabolic Analysis
58th Annual Meeting of the Biophysical-Society
CELL PRESS. 2014: 798A–798A
View details for Web of Science ID 000337000404482
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Photo-Activated Crosslinking Mass Spectrometry for Studying Biomolecular Interactions
58th Annual Meeting of the Biophysical-Society
CELL PRESS. 2014: 459A–459A
View details for Web of Science ID 000337000402555
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Is the simplest chemical reaction really so simple?
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2014; 111 (1): 15-20
Abstract
Modern computational methods have become so powerful for predicting the outcome for the H + H2 → H2 + H bimolecular exchange reaction that it might seem further experiments are not needed. Nevertheless, experiments have led the way to cause theorists to look more deeply into this simplest of all chemical reactions. The findings are less simple.
View details for DOI 10.1073/pnas.1315725111
View details for Web of Science ID 000329350700031
View details for PubMedID 24367084
View details for PubMedCentralID PMC3890794
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Modes of Activation of Organometallic Iridium Complexes for Catalytic Water and C-H Oxidation
INORGANIC CHEMISTRY
2014; 53 (1): 423-433
Abstract
Sodium periodate (NaIO4) is added to Cp*Ir(III) (Cp* = C5Me5(-)) or (cod)Ir(I) (cod = cyclooctadiene) complexes, which are water and C-H oxidation catalyst precursors, and the resulting aqueous reaction is investigated from milliseconds to seconds using desorption electrospray ionization, electrosonic spray ionization, and cryogenic ion vibrational predissociation spectroscopy. Extensive oxidation of the Cp* ligand is observed, likely beginning with electrophilic C-H hydroxylation of a Cp* methyl group followed by nonselective pathways of further oxidative degradation. Evidence is presented that the supporting chelate ligand in Cp*Ir(chelate) precursors influences the course of oxidation and is neither eliminated from the coordination sphere nor oxidatively transformed. Isomeric products of initial Cp* oxidation are identified and structurally characterized by vibrational spectroscopy in conjunction with density functional theory (DFT) modeling. Less extensive but more rapid oxidation of the cod ligand is also observed in the (cod)Ir(I) complexes. The observations are consistent with the proposed role of Cp* and cod as sacrificial placeholder ligands that are oxidatively removed from the precursor complexes under catalytic conditions.
View details for DOI 10.1021/ic402390t
View details for Web of Science ID 000329529800051
View details for PubMedID 24228617
- Coherent Superposition of M-States in a Single Rovibrational Level of H2 by Start-Induced Adiabatic Raman Passage J. Chem. Phys. 2014; 140: 074201
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A Compact Tandem Two-Step Laser Time-of-Flight Mass Spectrometer for In Situ Analysis of Non-Volatile Organics on Planetary Surfaces
IEEE. 2014
View details for Web of Science ID 000356039102023
- "In questo modo io scrivo" Aracne editrice. 2014
- Direct Synthesis of Protein-Incorporated Metal-Organic Framework Hybrid Materials NANO LETTERS 2014; 14: 5761-5765
- Do Identical Polar Diatomic Molecules Form Stacked or Linear Dimers? Do Identical Polar Diatomic Molecules Form Stacked or Linear Dimers? 2014: 704-712
- LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis 2014
- Molecular Assessment of Gastric Cancer Surgical Resection Margins by Mass Spectrometric Imaging Proc. Nat. Acad. Science 2014: 2436–2441
- Why Some Pool Shots Are More Difficult Than Others Resonance 2014; 19: 116-122
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Speciation and decomposition pathways of ruthenium catalysts used for selective C-H hydroxylation
CHEMICAL SCIENCE
2014; 5 (8): 3309-3314
View details for DOI 10.1039/c4sc01050g
View details for Web of Science ID 000338652900046
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Challenges of Metagenomics and Single-Cell Genomics Approaches for Exploring Cyanobacterial Diversity
Challenges of Metagenomics and Single-Cell Genomics Approaches for Exploring Cyanobacterial Diversity
2014
View details for DOI 10.1007/s11120-014-0066-9
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Laser-Based Mass Spectrometric Determination of Aggregation Numbers for Petroleum- and Coal-Derived Asphaltenes
ENERGY & FUELS
2014; 28 (1): 475-482
View details for DOI 10.1021/ef401958n
View details for Web of Science ID 000330018200052
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Diamondosomes: Submicron Colloidosomes with Nanodiamond Shells
Part. Part. System. Charact.
2014
View details for DOI 10.1002/ppsc.201400022
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Speciation and Decomposition Pathways of Ruthenium Catalysts Used for Selective C-H Hydroxylation
Chem. Sci.
2014; 5 (8): 3309-3314
View details for DOI 10.1039/C4SC01050G
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Measuring science
ISSUES IN SCIENCE AND TECHNOLOGY
2013; 29 (2): 13-14
View details for Web of Science ID 000329882500008
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Simultaneous Measurement of Reactive and Inelastic Scattering: Differential Cross Section of the H + HD -> HD(v ', j ') + H Reaction
ZEITSCHRIFT FUR PHYSIKALISCHE CHEMIE-INTERNATIONAL JOURNAL OF RESEARCH IN PHYSICAL CHEMISTRY & CHEMICAL PHYSICS
2013; 227 (9-11): 1281-1299
View details for DOI 10.1524/zpch.2013.0407
View details for Web of Science ID 000327861100008
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Hunt for geometric phase effects in H plus HD -> HD(v ', j ') plus H
JOURNAL OF CHEMICAL PHYSICS
2013; 139 (14)
Abstract
An attempt has been made to measure the theoretically predicted manifestation of a geometric phase in the differential cross section for the H + HD → HD(v' = 2, j' = 5) + H reaction at a center-of-mass collision energy of 1.44 eV (33.2 kcal∕mol). Minute oscillatory differences between calculated differential cross sections that take into account and ignore the effect of geometric phase have proven to be beyond our experimental resolution in spite of the collection of more than 44,000 ions.
View details for DOI 10.1063/1.4821601
View details for Web of Science ID 000325780800035
View details for PubMedID 24116628
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Rapid Detection of Phenol Using a Membrane Containing Laccase Nanoflowers
CHEMISTRY-AN ASIAN JOURNAL
2013; 8 (10): 2358-2360
View details for DOI 10.1002/asia.201300020
View details for Web of Science ID 000324748600011
View details for PubMedID 23423764
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Electrooxidation of alcohols catalyzed by amino alcohol ligated ruthenium complexes.
Journal of the American Chemical Society
2013; 135 (38): 14299-14305
Abstract
Ruthenium transfer hydrogenation catalysts physisorbed onto edge-plane graphite electrodes are active electrocatalysts for the oxidation of alcohols. Electrooxidation of CH3OH (1.23 M) in a buffered aqueous solution at pH 11.5 with [(η(6)-p-cymene)(η(2)-N,O-(1R,2S)-cis-1-amino-2-indanol)]Ru(II)Cl (2) on edge-plane graphite exhibits an onset current at 560 mV vs NHE. Koutecky-Levich analysis at 750 mV reveals a four-electron oxidation of methanol with a rate of 1.35 M(-1) s(-1). Mechanistic investigations by (1)H NMR, cyclic voltammetry, and desorption electrospray ionization mass spectrometry indicate that the electroxidation of methanol to generate formate is mediated by surface-supported Ru-oxo complexes.
View details for DOI 10.1021/ja4055564
View details for PubMedID 24044700
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Lysis of a Single Cyanobacterium for Whole Genome Amplification
MICROMACHINES
2013; 4 (3): 321-332
View details for DOI 10.3390/mi4030321
View details for Web of Science ID 000325021600003
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Optical preparation of H-2 rovibrational levels with almost complete population transfer
JOURNAL OF CHEMICAL PHYSICS
2013; 139 (7)
Abstract
Using stimulated Raman adiabatic passage (SARP), it is possible, in principle, to transfer all the population in a rovibrational level of an isolated diatomic molecule to an excited rovibrational level. We use an overlapping sequence of pump (532 nm) and dump (683 nm) single-mode laser pulses of unequal fluence to prepare isolated H2 molecules in a molecular beam. In a first series of experiments we were able to transfer more than half the population to an excited rovibrational level [N. Mukherjee, W. R. Dong, J. A. Harrison, and R. N. Zare, J. Chem. Phys. 138(5), 051101-1-051101-4 (2013)]. Since then, we have achieved almost complete transfer (97% ± 7%) of population from the H2 (v = 0, J = 0) ground rovibrational level to the H2 (v = 1, J = 0) excited rovibrational level. An explanation is presented of the SARP process and how these results are obtained.
View details for DOI 10.1063/1.4818526
View details for Web of Science ID 000323509900023
View details for PubMedID 23968084
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Minimization of fragmentation and aggregation by laser desorption laser ionization mass spectrometry.
Journal of the American Society for Mass Spectrometry
2013; 24 (7): 1116-1122
Abstract
Measuring average quantities in complex mixtures can be challenging for mass spectrometry, as it requires ionization and detection with nearly equivalent cross-section for all components, minimal matrix effect, and suppressed signal from fragments and aggregates. Fragments and aggregates are particularly troublesome for complex mixtures, where they can be incorrectly assigned as parent ions. Here we study fragmentation and aggregation in six aromatic model compounds as well as petroleum asphaltenes (a naturally occurring complex mixture) using two laser-based ionization techniques: surface assisted laser desorption ionization (SALDI), in which a single laser desorbs and ionizes solid analytes; and laser ionization laser desorption mass spectrometry (L(2)MS), in which desorption and ionization are separated spatially and temporally with independent lasers. Model compounds studied include molecules commonly used as matrices in single laser ionization techniques such as matrix assisted laser desorption ionization (MALDI). We find significant fragmentation and aggregation in SALDI, such that individual fragment and aggregate peaks are typically more intense than the parent peak. These fragment and aggregate peaks are expected in MALDI experiments employing these compounds as matrices. On the other hand, we observe no aggregation and only minimal fragmentation in L(2)MS. These results highlight some advantages of L(2)MS for analysis of complex mixtures such as asphaltenes.
View details for DOI 10.1007/s13361-013-0636-7
View details for PubMedID 23633019
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Sorting Inactivated Cells Using Cell-Imprinted Polymer Thin Films
ACS NANO
2013; 7 (7): 6031-6036
Abstract
Previous work showed that cell imprinting in a polydimethylsiloxane (PDMS) film produced artificial receptors to cells by template-assisted rearrangement of functional groups on the surface of the polymer thin film which facilitated cell capture in the polymer surface indentations by size, shape, and most importantly chemical recognition. We report here that inactivation of cells by treatment with formaldehyde (4%), or glutaraldehyde (2%), or a combination of the two leads to markedly improved capture selectivity (a factor of 3) when cells to be analyzed are inactivated in the same manner. The enhanced capture efficiency compared to living cells results from two factors: (1) rigidification of the cell surface through crosslinking of amine groups by the aldehyde; and (2) elimination of chemicals excreted from living cells which interfere with the fidelity of the cell imprinting process. Moreover, cell inactivation has the advantage of removing biohazard risks associated with working with virulent bacteria. These results are demonstrated using different strains of mycobacterium tuberculosis.
View details for DOI 10.1021/nn401768s
View details for Web of Science ID 000322417400045
View details for PubMedID 23725546
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Functional protein-organic/inorganic hybrid nanomaterials
WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
2013; 5 (4): 320-328
Abstract
Nanotechnology offers immense opportunities for regulating and improving biological functions of proteins in vitro. Recent years have witnessed growing efforts to develop protein-incorporated hybrid nanostructured materials with potential applications in functional materials, enzymatic catalysis, drug delivery, and analytical sciences. In this review, recent advances in functional protein-organic/inorganic hybrid nanomaterials are discussed with an emphasis on the novel preparation methods, resulting nanostructures, and their potential applications in drug delivery and enzymatic catalysis. Future directions toward the rational design of these bionanomaterials are suggested.
View details for DOI 10.1002/wnan.1210
View details for Web of Science ID 000320403500003
View details for PubMedID 23362008
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Chemoselective pd-catalyzed oxidation of polyols: synthetic scope and mechanistic studies.
Journal of the American Chemical Society
2013; 135 (20): 7593-7602
Abstract
The regio- and chemoselective oxidation of unprotected vicinal polyols with [(neocuproine)Pd(OAc)]2(OTf)2 (1) (neocuproine = 2,9-dimethyl-1,10-phenanthroline) occurs readily under mild reaction conditions to generate α-hydroxy ketones. The oxidation of vicinal diols is both faster and more selective than the oxidation of primary and secondary alcohols; vicinal 1,2-diols are oxidized selectively to hydroxy ketones, whereas primary alcohols are oxidized in preference to secondary alcohols. Oxidative lactonization of 1,5-diols yields cyclic lactones. Catalyst loadings as low as 0.12 mol % in oxidation reactions on a 10 g scale can be used. The exquisite selectivity of this catalyst system is evident in the chemoselective and stereospecific oxidation of the polyol (S,S)-1,2,3,4-tetrahydroxybutane [(S,S)-threitol] to (S)-erythrulose. Mechanistic, kinetic, and theoretical studies revealed that the rate laws for the oxidation of primary and secondary alcohols differ from those of diols. Density functional theory calculations support the conclusion that β-hydride elimination to give hydroxy ketones is product-determining for the oxidation of vicinal diols, whereas for primary and secondary alcohols, pre-equilibria favoring primary alkoxides are product-determining. In situ desorption electrospray ionization mass spectrometry (DESI-MS) revealed several key intermediates in the proposed catalytic cycle.
View details for DOI 10.1021/ja4008694
View details for PubMedID 23659308
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Characterization of MYC-Induced Tumorigenesis by in Situ Lipid Profiling
ANALYTICAL CHEMISTRY
2013; 85 (9): 4259-4262
Abstract
We apply desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to provide an in situ lipidomic profile of genetically modified tissues from a conditional transgenic mouse model of MYC-induced hepatocellular carcinoma (HCC). This unique, label-free approach of combining DESI-MSI with the ability to turn specific genes on and off has led to the discovery of highly specific lipid molecules associated with MYC-induced tumor onset. We are able to distinguish normal from MYC-induced malignant cells. Our approach provides a strategy to define a precise molecular picture at a resolution of about 200 μm that may be useful in identifying lipid molecules that define how the MYC oncogene initiates and maintains tumorigenesis.
View details for DOI 10.1021/ac400479j
View details for Web of Science ID 000318756100008
View details for PubMedID 23560736
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Desorption electrospray ionization mass spectrometry studies of the chemoselective Pd-catalyzed aerobic oxidation of polyols
AMER CHEMICAL SOC. 2013
View details for Web of Science ID 000324303601085
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Disagreement between theory and experiment grows with increasing rotational excitation of HD(v ', j ') product for the H + D-2 reaction
JOURNAL OF CHEMICAL PHYSICS
2013; 138 (9)
Abstract
The Photoloc technique has been employed to measure the state-resolved differential cross sections of the HD(v', j(')) product in the reaction H + D2 over a wide range of collision energies and internal states. The experimental results were compared with fully dimensional, time-dependent quantum mechanical calculations on the refined Boothroyd-Keogh-Martin-Peterson potential energy surface. We find nearly perfect agreement between theory and experiment for HD(v', j(')) product states with low to medium rotational excitation, e.g., HD(v' = 1, j(') = 3) at a collision energy, Ecoll, of 1.72 eV, HD(v' = 1, j(') = 3, 5) at Ecoll = 1.97 eV, and HD(v' = 3, j(') = 3) at Ecoll = 1.97 eV. As the rotational angular momentum, j('), of HD(v', j(')) increases, the agreement between theoretical predictions and experimental measurements worsens but not in a simple fashion. A moderate disagreement between theory and experiment has been found for HD(v' = 0, j(') = 12) at Ecoll = 1.76 eV and increased monotonically for HD(v' = 0, j(') = 13) at Ecoll = 1.74 eV, HD(v' = 0, j(') = 14) at Ecoll = 1.72 eV, and HD(v' = 0, j(') = 15) at Ecoll = 1.70 eV. Disagreement was not limited to vibrationless HD(v', j(')) product states: HD(v' = 1, j(') = 12) at Ecoll = 1.60 eV and HD(v' = 3, j(') = 8, 10) at Ecoll = 1.97 eV followed a similar trend. Theoretical calculations suggest more sideways∕forward scattering than has been observed experimentally for high j(') HD(v', j(')) states. The source of this discrepancy is presently unknown but might be the result of inaccuracy in the potential energy surface.
View details for DOI 10.1063/1.4793557
View details for Web of Science ID 000315874200028
View details for PubMedID 23485297
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Preparing amorphous hydrophobic drug nanoparticles by nanoporous membrane extrusion
NANOMEDICINE
2013; 8 (3): 333-341
Abstract
The aim of the present study was to develop a simple and straightforward method for formulating hydrophobic drugs into nanoparticulate form in a scalable and inexpensive manner.The nanoporous membrane extrusion (NME) method was used to prepare hydrophobic drug nanoparticles. NME is based on the induced precipitation of drug-loaded nanoparticles at the exits of nanopores. Three common hydrophobic drug models (silymarin, β-carotene and butylated hydroxytoluene) were tested. The authors carefully investigated the morphology, crystallinity and dissolution profile of the resulting nanoparticles.Using NME, the authors successfully prepared rather uniform drug nanoparticles (∼100 nm in diameter). These nanoparticles were amorphous and show an improved dissolution profile compared with untreated drug powders.These studies suggest that NME could be used as a general method to produce nanoparticles of hydrophobic drugs.
View details for DOI 10.2217/NNM.12.119
View details for Web of Science ID 000315973900012
View details for PubMedID 22943127
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Communication: Transfer of more than half the population to a selected rovibrational state of H-2 by Stark-induced adiabatic Raman passage
JOURNAL OF CHEMICAL PHYSICS
2013; 138 (5)
Abstract
By using Stark-induced adiabatic Raman passage (SARP) with partially overlapping nanosecond pump (532 nm) and Stokes (683 nm) laser pulses, 73% ± 6% of the initial ground vibrational state population of H(2) (v = 0, J = 0) is transferred to the single vibrationally excited eigenstate (v = 1, J = 0). In contrast to other Stark chirped Raman adiabatic passage techniques, SARP transfers population from the initial ground state to a vibrationally excited target state of the ground electronic surface without using an intermediate vibronic resonance within an upper electronic state. Parallel linearly polarized, co-propagating pump and Stokes laser pulses of respective durations 6 ns and 4.5 ns, are combined with a relative delay of ~4 ns before orthogonally intersecting the molecular beam of H(2). The pump and Stokes laser pulses have fluences of ~10 J/mm(2) and ~1 J/mm(2), respectively. The intense pump pulse generates the necessary sweeping of the Raman resonance frequency by ac (second-order) Stark shifting the rovibrational levels. As the frequency of the v = 0 → v = 1 Raman transition is swept through resonance in the presence of the strong pump and the weaker delayed Stokes pulses, the population of (v = 0, J = 0) is coherently transferred via an adiabatic passage to (v = 1, J = 0). A quantitative measure of the population transferred to the target state is obtained from the depletion of the ground-state population using 2 + 1 resonance enhanced multiphoton ionization (REMPI) in a time-of-flight mass spectrometer. The depletion is measured by comparing the REMPI signal of (v = 0, J = 0) at Raman resonance with that obtained when the Stokes pulse is detuned from the Stark-shifted Raman resonance. No depletion is observed with either the pump or the Stokes pulses alone, confirming that the measured depletion is indeed caused by the SARP-induced population transfer from the ground to the target state and not by the loss of molecules from photoionization or photodissociation. The two-photon resonant UV pulse used for REMPI detection is delayed by 20 ns with respect to the pump pulse to avoid the ac Stark shift originating from the pump and Stokes laser pulses. This experiment demonstrates the feasibility of preparing a large ensemble of isolated molecules in a preselected single quantum state without requiring an intermediate vibronic resonance.
View details for DOI 10.1063/1.4790402
View details for Web of Science ID 000314746400001
View details for PubMedID 23406090
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The Hydrogen Games and Other Adventures in Chemistry
ANNUAL REVIEW OF PHYSICAL CHEMISTRY, VOL 64
2013; 64: 1-19
Abstract
I seem to have started off on the wrong foot in life, but I am extremely fortunate that I soon found my footing in the company of physical chemists. I consider myself to be very lucky to be doing something that constantly brings me in contact with bright minds, stimulating conversations, and exciting experiments. My work has allowed me to learn astounding facts about the molecules and atoms that make up our surroundings and ourselves. For this article, I focus on one aspect of my research, understanding the fundamental principles of the simple reaction between a hydrogen atom and a hydrogen molecule. Although my group and others have been studying this seemingly simple reaction for well over 30 years, it continues to provoke questions about the properties of matter.
View details for DOI 10.1146/annurev-physchem-040412-110115
View details for Web of Science ID 000321771600001
View details for PubMedID 22974411
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American universities at risk.
Angewandte Chemie (International ed. in English)
2013; 52 (1): 112–13
View details for PubMedID 23208762
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Temperature-responsive enzyme-polymer nanoconjugates with enhanced catalytic activities in organic media
CHEMICAL COMMUNICATIONS
2013; 49 (54): 6090-6092
Abstract
A general approach for preparing enzyme-polymer nanoconjugates that respond to temperature in organic media is presented. These nanoconjugates readily dissolve in organic solvents for homogenous catalysis at 40 °C and showed greatly enhanced apparent catalytic activities. The recovery of the soluble enzyme-polymer nanoconjugates is accomplished by temperature-induced precipitation.
View details for DOI 10.1039/c3cc42493f
View details for Web of Science ID 000320199000027
View details for PubMedID 23727906
- Temperature-Responsive Enzyme-Polymer Nanoconjugates with Enhanced Catalytic Activities in Organic Solvents ChemComm 2013; 49: 6090-6092
- Optical Preparation of H2 Rovibrational Levels with Almost Complete Population Transfer J. Chem. Phys. 2013; 139
- Sorting Inactivated Celss Using Cell-Imprinted Polymer Thin Films ACS Nano 2013; 7: 6031-6036
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Protein-Polymer Hybrid Nanoparticles for Drug Delivery
SMALL
2012; 8 (23): 3573-3578
Abstract
Amphiphilic bovine serum albumin-poly(methyl methacrylate) conjugate forms nanoparticles with the uniform size of ~100 nm by self-assembling. Loaded with the hydrophobic anti-tumor drug camptothecin, the nanoparticle efficiently delivers drugs into cancer cells, and thus inhibits ~79% of tumor growth in animals compared with free drug.
View details for DOI 10.1002/smll.201200889
View details for Web of Science ID 000312214400004
View details for PubMedID 22888073
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Capturing fleeting intermediates in a catalytic C-H amination reaction cycle
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2012; 109 (45): 18295-18299
Abstract
We have applied an ambient ionization technique, desorption electrospray ionization MS, to identify transient reactive species of an archetypal C-H amination reaction catalyzed by a dirhodium tetracarboxylate complex. Using this analytical method, we have detected previously proposed short-lived reaction intermediates, including two nitrenoid complexes that differ in oxidation state. Our findings suggest that an Rh-nitrene oxidant can react with hydrocarbon substrates through a hydrogen atom abstraction pathway and raise the intriguing possibility that two catalytic C-H amination pathways may be operative in a typical bulk solution reaction. As highlighted by these results, desorption electrospray ionization MS should have broad applicability for the mechanistic study of catalytic processes.
View details for DOI 10.1073/pnas.1207600109
View details for Web of Science ID 000311156700025
View details for PubMedID 23091019
View details for PubMedCentralID PMC3494934
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H + D-2 Reaction Dynamics in the Limit of Low Product Recoil Energy
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
2012; 3 (20): 2959-2963
View details for DOI 10.1021/jz301192f
View details for Web of Science ID 000310177200007
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Isomeric differentiation of polycyclic aromatic hydrocarbons using silver nitrate reactive desorption electrospray ionization mass spectrometry
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
2012; 26 (17): 1985-1992
Abstract
Polycyclic aromatic hydrocarbons (PAHs) are nonpolar and difficult to detect by desorption electrospray ionization. We present a new detection method based on cationization with silver ions, which has the added advantage of being able to differentiate PAHs with the same mass but different structure.9,10-Diphenylanthracene and triptycene, in addition to four different groups of PAH isomers: (1) anthracene and phenanthrene, (2) pyrene and fluoranthene, (3) benz[a]anthracene, benz[b]anthracene (tetracene), and chrysene (4) benzo[a]pyrene and benzo[k]fluoranthene, were deposited on a paper surface and bombarded with methanol droplets containing silver nitrate. The resulting microdroplets entered a quadruple mass spectrometer for mass analysis.The mass spectrum shows [PAH](+), [Ag + OH + PAH](+), and [Ag(PAH)(n)](+) (n = 1, 2) (and [PAH + O(2)](+) in the case of benz[b]anthracene) ions. PAHs having a bay structure, such as phenanthrene, showed a different tendency to interact with silver ions from those PAHs having a linear arrangement of the fused benzene rings, such as anthracene. The ratios of the [PAH](+) peak intensity to that of [Ag-PAH](+), [Ag + OH + PAH](+), [Ag(PAH)(2)](+), and [PAH + O(2)](+) were used to differentiate the PAH isomers sharing the same molecular formula with different structures. For isomeric mixtures the [PAH](+) to [Ag + OH + PAH](+) ratio was found to be the most useful parameter. The uncertainty in the mole fraction of an isomeric mixture was ±0.09, ±0.13, ±0.25, and ±0.1 for phenanthrene-anthracene, fluoranthene-pyrene, benz[a]anthracene-chrysene, and benzo[a]pyrene-benzo[k]fluoranthene, respectively.A simple method has been developed for the detection of PAHs in desorption electrospray ionization mass spectrometry based on Ag(I) cationization. The method showed a capability to differentiate PAHs isomers (having the same molecular mass) in isomeric mixture with an uncertainty in the mole fraction of about ±0.1. At high inlet temperature and voltage, this method showed better sensitivity but less ability to differentiate between isomeric species.
View details for DOI 10.1002/rcm.6309
View details for Web of Science ID 000306964600011
View details for PubMedID 22847697
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A Reduced Organic Carbon Component in Martian Basalts
SCIENCE
2012; 337 (6091): 212-215
Abstract
The source and nature of carbon on Mars have been a subject of intense speculation. We report the results of confocal Raman imaging spectroscopy on 11 martian meteorites, spanning about 4.2 billion years of martian history. Ten of the meteorites contain abiotic macromolecular carbon (MMC) phases detected in association with small oxide grains included within high-temperature minerals. Polycyclic aromatic hydrocarbons were detected along with MMC phases in Dar al Gani 476. The association of organic carbon within magmatic minerals indicates that martian magmas favored precipitation of reduced carbon species during crystallization. The ubiquitous distribution of abiotic organic carbon in martian igneous rocks is important for understanding the martian carbon cycle and has implications for future missions to detect possible past martian life.
View details for DOI 10.1126/science.1220715
View details for Web of Science ID 000306323500053
View details for PubMedID 22628557
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Protein-inorganic hybrid nanoflowers
NATURE NANOTECHNOLOGY
2012; 7 (7): 428-432
Abstract
Flower-shaped inorganic nanocrystals have been used for applications in catalysis and analytical science, but so far there have been no reports of 'nanoflowers' made of organic components. Here, we report a method for creating hybrid organic-inorganic nanoflowers using copper (II) ions as the inorganic component and various proteins as the organic component. The protein molecules form complexes with the copper ions, and these complexes become nucleation sites for primary crystals of copper phosphate. Interaction between the protein and copper ions then leads to the growth of micrometre-sized particles that have nanoscale features and that are shaped like flower petals. When an enzyme is used as the protein component of the hybrid nanoflower, it exhibits enhanced enzymatic activity and stability compared with the free enzyme. This is attributed to the high surface area and confinement of the enzymes in the nanoflowers.
View details for DOI 10.1038/NNANO.2012.80
View details for Web of Science ID 000306112000008
View details for PubMedID 22659609
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Advances in Asphaltene Science and the Yen-Mullins Model
ENERGY & FUELS
2012; 26 (7): 3986-4003
View details for DOI 10.1021/ef300185p
View details for Web of Science ID 000306503100004
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Seemingly Anomalous Angular Distributions in H+D-2 Reactive Scattering
SCIENCE
2012; 336 (6089): 1687-1690
Abstract
When a hydrogen (H) atom approaches a deuterium (D(2)) molecule, the minimum-energy path is for the three nuclei to line up. Consequently, nearly collinear collisions cause HD reaction products to be backscattered with low rotational excitation, whereas more glancing collisions yield sideways-scattered HD products with higher rotational excitation. Here we report that measured cross sections for the H + D(2) → HD(v' = 4, j') + D reaction at a collision energy of 1.97 electron volts contradict this behavior. The anomalous angular distributions match closely fully quantum mechanical calculations, and for the most part quasiclassical trajectory calculations. As the energy available in product recoil is reduced, a rotational barrier to reaction cuts off contributions from glancing collisions, causing high-j' HD products to become backward scattered.
View details for DOI 10.1126/science.1221329
View details for Web of Science ID 000305794500045
View details for PubMedID 22745425
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Laser Desorption Single-Photon Ionization of Asphaltenes: Mass Range, Compound Sensitivity, and Matrix Effects
ENERGY & FUELS
2012; 26 (6): 3521-3526
View details for DOI 10.1021/ef3002313
View details for Web of Science ID 000305444400044
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Chemical Recognition in Cell-Imprinted Polymers
ACS NANO
2012; 6 (5): 4314-4318
Abstract
A glass slide covered with bacteria is pressed into another glass slide coated with partially cured polydimethylsiloxane (PDMS). The PDMS is hardened and the cells are removed to create a textured surface whose indentations preferentially capture the same type of bacteria when a mixture of bacteria is flowed over it. Overcoating the cell-imprinted PDMS with methylsilane groups causes the resulting surface to lose much of its ability to preferentially capture the imprinted bacteria, although the shapes of the imprints, measured by atomic force field microscopy, are shown to be hardly affected. We interpret this behavior as strong evidence that chemical recognition plays a dominant role in cell sorting with cell-imprinted PDMS polymer films.
View details for DOI 10.1021/nn300901z
View details for Web of Science ID 000304231700073
View details for PubMedID 22468923
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Surface-imprinted polymers in microfluidic devices
SCIENCE CHINA-CHEMISTRY
2012; 55 (4): 469-483
View details for DOI 10.1007/s11426-012-4544-7
View details for Web of Science ID 000303184300003
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What is the origin for homochirality in earth's biomolecules?
AMER CHEMICAL SOC. 2012
View details for Web of Science ID 000324503203309
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ANALYTICAL CHEMISTRY Ultrasensitive radiocarbon detection
NATURE
2012; 482 (7385): 312-313
View details for Web of Science ID 000300287100027
View details for PubMedID 22337044
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Transient Ru-methyl formate intermediates generated with bifunctional transfer hydrogenation catalysts
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2012; 109 (7): 2246-2250
Abstract
Desorption electrospray ionization (DESI) coupled to high-resolution Orbitrap mass spectrometry (MS) was used to study the reactivity of a (β-amino alcohol)(arene)RuCl transfer hydrogenation catalytic precursor in methanol (CH(3)OH). By placing [(p-cymene)RuCl(2)](2) on a surface and spraying a solution of β-amino alcohol in methanol, two unique transient intermediates having lifetimes in the submillisecond to millisecond range were detected. These intermediates were identified as Ru (II) and Ru (IV) complexes incorporating methyl formate (HCOOCH(3)). The Ru (IV) intermediate is not observed when the DESI spray solution is sparged with Ar gas, indicating that O(2) dissolved in the solvent is necessary for oxidizing Ru (II) to Ru (IV). These proposed intermediates are supported by high-resolution and high mass accuracy measurements and by comparing experimental to calculated isotope profiles. Additionally, analyzing the bulk reaction mixture using gas chromatography-MS and nuclear magnetic resonance spectroscopy confirms the formation of HCOOCH(3). These results represent an example that species generated from the (β-amino alcohol)(arene)RuCl (II) catalytic precursor can selectively oxidize CH(3)OH to HCOOCH(3). This observation leads us to propose a pathway that can compete with the hydrogen transfer catalytic cycle. Although bifunctional hydrogen transfer with Ru catalysts has been well-studied, the ability of DESI to intercept intermediates formed in the first few milliseconds of a chemical reaction allowed identification of previously unrecognized intermediates and reaction pathways in this catalytic system.
View details for DOI 10.1073/pnas.1118934109
View details for Web of Science ID 000300489200024
View details for PubMedID 22315417
View details for PubMedCentralID PMC3289342
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Electrical, Optical, and Docking Properties of Conical Nanopores
ACS NANO
2012; 6 (2): 993-997
Abstract
The diffusion-influenced translocation behavior of individual nanoparticles upon passage through a conical nanopore has been elucidated by using a pressure-reversal, resistive-pulse technique, as reported by Lan and White in this issue of ACS Nano. We outline here some recent progress in conical nanopore analysis, and we present some prospects for future developments. Compared to cylindrical nanopores, the geometric change brought about by tapered nanopores causes a dramatic difference in electrical and optical properties. Such conical nanopores may also be integrated into microfluidic chips to capture cells or nanoparticles, one per nanopore, and then to release them. These advances hold the promise of making conical nanopores useful as highly efficient actuators and sensors.
View details for DOI 10.1021/nn300356d
View details for Web of Science ID 000300757900001
View details for PubMedID 22304827
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Microfluidic capture and release of bacteria in a conical nanopore array
LAB ON A CHIP
2012; 12 (3): 558-561
Abstract
We present a simple and inexpensive method for the capture and release of bacteria contained in an array of conical nanopores on a membrane inside a microfluidic device. As an example, we demonstrate that cyanobacteria can be captured, one bacterium per pore, in a defined orientation with over 500 bacteria per membrane with viabilities as high as 100%. The device can also specifically capture cyanobacteria from a mixed suspension of cyanobacteria and chlamydomonas with a selectivity as high as 90%.
View details for DOI 10.1039/c2lc21092d
View details for Web of Science ID 000298964300015
View details for PubMedID 22170441
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Editorial: Assessing Academic Researchers
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2012; 51 (30): 7338-7339
View details for DOI 10.1002/anie.201201011
View details for Web of Science ID 000306511600001
View details for PubMedID 22513978
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D+C(CH3)(4) -> HD (v ', j ')+C(CH3)(3)CH2: possible concerted flow of vibration energy into translation
MOLECULAR PHYSICS
2012; 110 (15-16): 1713-1720
View details for DOI 10.1080/00268976.2012.673641
View details for Web of Science ID 000307645400017
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Reaction dynamics: concluding remarks
FARADAY DISCUSSIONS
2012; 157: 501-504
Abstract
The 157th Faraday Discussion represented a historic turning point in the development of the field of reaction dynamics because it concerned itself with how reactions occur in gases, in liquid, and at interfaces. Never before has the attempt been made to unify the various approaches to reaction dynamics in one Faraday Discussion meeting and to discover what language was common and what was special to these previously distinct subdisciplines. This Discussion also marked a maturation of the field of reaction dynamics in that so much emphasis was placed on what the combination of theory and experiment could tell us about the detailed course of chemical transformations.
View details for DOI 10.1039/c2fd20120h
View details for Web of Science ID 000309137600028
View details for PubMedID 23230784
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Drug Release from Electric-Field-Responsive Nanoparticles
ACS NANO
2012; 6 (1): 227-233
Abstract
We describe a new temperature and electric field dual-stimulus responsive nanoparticle system for programmed drug delivery. Nanoparticles of a conducting polymer (polypyrrole) are loaded with therapeutic pharmaceuticals and are subcutaneously localized in vivo with the assistance of a temperature-sensitive hydrogel (PLGA-PEG-PLGA). We have shown that drug release from the conductive nanoparticles is controlled by the application of a weak, external DC electric field. This approach represents a novel interactive drug delivery system that can show an externally tailored release profile with an excellent spatial, temporal, and dosage control.
View details for DOI 10.1021/nn203430m
View details for Web of Science ID 000299368300029
View details for PubMedID 22111891
View details for PubMedCentralID PMC3489921
- H + D2 Reaction Dynamics in the Limit of the Low Product Recoil Energy J. Phys. Chem. Lett. 2012; 3: 2959-2963
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My Life with LIF: A Personal Account of Developing Laser-Induced Fluorescence
ANNUAL REVIEW OF ANALYTICAL CHEMISTRY, VOL 5
2012; 5: 1-14
Abstract
Laser-induced fluorescence (LIF) is a spectroscopic technique that involves the excitation of a molecular target by a beam of laser radiation followed by the detection of the subsequent emission of radiation from the target. LIF detection has several advantages over absorption spectroscopy. First, LIF has excellent detection sensitivity because a signal is observed against a dark background. Second, the emitted radiation can be collected at various angles with respect to the incoming laser beam, making it possible to obtain two- and three-dimensional images because the fluorescence is emitted in all directions. Third, by dispersing the fluorescence, it is also possible to learn about the transitions from the state excited to the various lower levels of the target species. Finally, because of the delay between the excitation and detection events, it is also possible to learn about what processes the excited target undergoes in the intervening time.
View details for DOI 10.1146/annurev-anchem-062011-143148
View details for Web of Science ID 000307956200002
View details for PubMedID 22149473
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Separation of bacteria with imprinted polymeric films
ANALYST
2012; 137 (6): 1495-1499
Abstract
Separation of compounds out of complex mixtures is a key issue that has been solved for small molecules by chromatography. However, general methods for the separation of large bio-particles, such as cells, are still challenging. We demonstrate integration of imprinted polymeric films (IPF) into a microfluidic chip, which preferentially capture cells matching an imprint template, and separate strains of cyanobacteria with 80-90% efficiency, despite a minimal difference in morphology and fluorescence, demonstrating its general nature. It is currently thought that the imprinting process, conducted while the polymer cures, transfers chemical information of the cell's external structure to the substrate. Capture specificity and separation can be further enhanced by orienting the imprints parallel to the flow vector and tuning the pH to a lower range.
View details for DOI 10.1039/c2an15927a
View details for Web of Science ID 000300510900030
View details for PubMedID 22324051
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In Vivo Sustained Release of siRNA from Solid Lipid Nanoparticles
ACS NANO
2011; 5 (12): 9977-9983
Abstract
Small interfering RNA (siRNA) is a highly potent drug in gene-based therapy with a challenge of being delivered in a sustained manner. Nanoparticle drug delivery systems allow for incorporating and controlled release of therapeutic payloads. We demonstrate that solid lipid nanoparticles can incorporate and provide sustained release of siRNA. Tristearin solid lipid nanoparticles, made by nanoprecipitation, were loaded with siRNA (4.4-5.5 wt % loading ratio) using a hydrophobic ion pairing approach that employs the cationic lipid DOTAP. Intradermal injection of these nanocarriers in mouse footpads resulted in prolonged siRNA release over a period of 10-13 days. In vitro cell studies showed that the released siRNA retained its activity. Nanoparticles developed in this study offer an alternative approach to polymeric nanoparticles for encapsulation and sustained delivery of siRNA with the advantage of being prepared from physiologically well-tolerated materials.
View details for DOI 10.1021/nn203745n
View details for Web of Science ID 000298316700073
View details for PubMedID 22077198
View details for PubMedCentralID PMC3246574
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Can stimulated Raman pumping cause large population transfers in isolated molecules?
JOURNAL OF CHEMICAL PHYSICS
2011; 135 (18)
Abstract
When stimulated Raman pumping (SRP) is applied to a stream of isolated molecules, such as found in a supersonic molecular beam expansion, we show that SRP can neither saturate nor power broaden a molecular transition connecting two metastable levels that is resonant with the energy difference between the pump and Stokes laser pulses. Using the optical Bloch-Feynman equations, we discuss the pumping of the hydrogen molecule from H(2) (v = 0, J = 0, M = 0) to H(2) (v = 1, J = 2, M = 0) as an illustration of how coherent population return severely reduces the SRP pumping efficiency unless the pump and Stokes laser pulses are applied with an appropriate relative delay and ratio of intensities.
View details for DOI 10.1063/1.3657832
View details for Web of Science ID 000297472800016
View details for PubMedID 22088058
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Competencies: A Cure for Pre-Med Curriculum
SCIENCE
2011; 334 (6057): 760-761
View details for Web of Science ID 000296849600022
View details for PubMedID 22076362
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China's Science Funding
SCIENCE
2011; 334 (6055): 433
View details for DOI 10.1126/science.1214042
View details for Web of Science ID 000296230500001
View details for PubMedID 22034401
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Glucose-Driven Fuel Cell Constructed from Enzymes and Filter Paper
JOURNAL OF CHEMICAL EDUCATION
2011; 88 (9): 1283-1286
View details for DOI 10.1021/ed100967j
View details for Web of Science ID 000293813100021
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Stark-induced adiabatic Raman passage for preparing polarized molecules
JOURNAL OF CHEMICAL PHYSICS
2011; 135 (2)
Abstract
We propose a method based on Stark-induced adiabatic Raman passage (SARP) for preparing vibrationally excited molecules with known orientation and alignment for future dynamical stereochemistry studies. This method utilizes the (J, M)-state dependent dynamic Stark shifts of rovibrational levels induced by delayed but overlapping pump and Stokes pulses of unequal intensities. Under collision-free conditions, our calculations show that we can achieve complete population transfer to an excited vibrational level (v > 0) of the H(2) molecule in its ground electronic state. Specifically, the H(2) (v = 1, J = 2, M = 0) level can be prepared with complete population transfer from the (v = 0, J = 0, M = 0) level using the S(0) branch of the Raman transition with visible pump and Stoke laser pulses, each polarized parallel to the z axis (uniaxial π-π Raman pumping). Similarly, H(2) (v = 1, J = 2, M = ±2) can be prepared using SARP with a left circularly polarized pump and a right circularly (or vice versa) polarized Stokes wave propagating along the z axis (σ(±)-σ(∓) Raman pumping). This technique requires phase coherent nanosecond pulses with unequal intensity between the pump and the Stokes pulses, one being four or more times greater than the other. A peak intensity of ~16 GW/cm(2) for the stronger pulse is required to generate the desirable sweep of the Raman resonance frequency. These conditions may be fulfilled using red and green laser pulses with the duration of a few nanoseconds and optical energies of ~12 and 60 mJ within a focused beam of diameter ~0.25 mm. Additionally, complete population transfer to the v = 4 vibrational level is predicted to be possible using SARP with a 355-nm pump and a near infrared Stokes laser with accessible pulse energies.
View details for DOI 10.1063/1.3599711
View details for Web of Science ID 000292776000017
View details for PubMedID 21766932
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False estimates of stimulated Raman pumping efficiency caused by the optical Stark effect
JOURNAL OF CHEMICAL PHYSICS
2011; 134 (23)
Abstract
One technique for measuring the fraction of molecules pumped to the excited state in stimulated Raman pumping (SRP) is to record the depletion of molecules in the lower state by resonance enhanced multiphoton ionization (REMPI). The presence of electric fields on the order of 10(7) V/cm arising from the pulsed SRP laser beams is sufficient to shift the line position of the REMPI transition to such an extent that the estimate of the pumping efficiency is overestimated unless this shift is accounted for.
View details for DOI 10.1063/1.3601923
View details for Web of Science ID 000291992500019
View details for PubMedID 21702559
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Bovine Serum Albumin-Poly(methyl methacrylate) Nanoparticles: An Example of Frustrated Phase Separation
NANO LETTERS
2011; 11 (6): 2551-2554
Abstract
A new protein-polymer conjugate made of denatured bovine serum albumin (BSA) covalently bonded to poly(methyl methacrylate) (PMMA) is synthesized by attaching PMMA to acryloylated BSA followed by nanoparticle precipitation. Depending on the BSA to PMMA ratio, these conjugates self-assemble into uniform spherical nanoparticles which show "island" growth on the surface of the nanoparticles. This growth is promoted or retarded by exposing the nanoparticles to different solvents, causing the two components to undergo incipient phase separation. Incipient phase separation of the BSA-PMMA conjugate two-component system was observed in single nanoparticles, resulting in "island" growth on the surface of the nanoparticles. Incipient phase separation of the BSA-PMMA conjugate two-component system was observed in single nanoparticles, resulting in "island" growth on the surface of the nanoparticles.
View details for DOI 10.1021/nl201303q
View details for Web of Science ID 000291322600062
View details for PubMedID 21553851
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Nanoparticle PEGylation for imaging and therapy
NANOMEDICINE
2011; 6 (4): 715-728
Abstract
Nanoparticles are an essential component in the emerging field of nanomedical imaging and therapy. When deployed in vivo, these materials are typically protected from the immune system by polyethylene glycol (PEG). A wide variety of strategies to coat and characterize nanoparticles with PEG has established important trends on PEG size, shape, density, loading level, molecular weight, charge and purification. Strategies to incorporate targeting ligands are also prevalent. This article presents a background to investigators new to stealth nanoparticles, and suggests some key considerations needed prior to designing a nanoparticle PEGylation protocol and characterizing the performance features of the product.
View details for DOI 10.2217/NNM.11.19
View details for Web of Science ID 000292994300019
View details for PubMedID 21718180
View details for PubMedCentralID PMC3217316
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Evidence for Island Structures as the Dominant Architecture of Asphaltenes
ENERGY & FUELS
2011; 25 (4): 1597-1604
View details for DOI 10.1021/ef101522w
View details for Web of Science ID 000289697700030
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Whole gene amplification and protein separation from a few cells
ANALYTICAL BIOCHEMISTRY
2011; 411 (1): 64-70
Abstract
Despite the growing interest to explore untapped microbial gene and protein diversity, no single platform has been able to acquire both gene and protein information from just a few cells. We present a microfluidic system that simultaneously performs on-chip capillary electrophoresis for protein analysis and whole genome amplification (WGA), and we demonstrate this by doing both for the same cohort of cyanobacterial cells. This technology opens avenues for studying protein profiles of precious environmental microbial samples and simultaneously accessing genomic information based on WGA.
View details for DOI 10.1016/j.ab.2010.12.028
View details for Web of Science ID 000287618900009
View details for PubMedID 21185803
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Interfacing Capillary-Based Separations to Mass Spectrometry Using Desorption Electrospray Ionization
ANALYTICAL CHEMISTRY
2011; 83 (6): 1955-1959
Abstract
The powerful hybrid analysis method of capillary-based separations followed by mass spectrometric analysis gives substantial chemical identity and structural information. It is usually carried out using electrospray ionization. However, the salts and detergents used in the mobile phase for electrokinetic separations suppress ionization efficiencies and contaminate the inlet of the mass spectrometer. This report describes a new method that uses desorption electrospray ionization (DESI) to overcome these limitations. Effluent from capillary columns is deposited on a rotating Teflon disk that is covered with paper. As the surface rotates, the temporal separation of the eluting analytes (i.e., the electropherogram) is spatially encoded on the surface. Then, using DESI, surface-deposited analytes are preferentially ionized, reducing the effects of ion suppression and inlet contamination on signal. With the use of this novel approach, two capillary-based separations were performed: a mixture of the rhodamine dyes at milligram/milliliter levels in a 10 mM sodium borate solution was separated by capillary electrophoresis, and a mixture of three cardiac drugs at milligram/milliliter levels in a 12.5 mM sodium borate and 12.5 mM sodium dodecyl sulfate solution was separated by micellar electrokinetic chromatography. In both experiments, the negative effects of detergents and salts on the MS analyses were minimized.
View details for DOI 10.1021/ac102648k
View details for Web of Science ID 000288182900014
View details for PubMedID 21319740
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Preparation of Mineralized Nanofibers: Collagen Fibrils Containing Calcium Phosphate
NANO LETTERS
2011; 11 (3): 1383-1388
Abstract
We report a straightforward, bottom-up, scalable process for preparing mineralized nanofibers. Our procedure is based on flowing feed solution, containing both inorganic cations and polymeric molecules, through a nanoporous membrane into a receiver solution with anions, which leads to the formation of mineralized nanofibers at the exit of the pores. With this strategy, we were able to achieve size control of the nanofiber diameters. We illustrate this approach by producing collagen fibrils with calcium phosphate incorporated inside the fibrils. This structure, which resembles the basic constituent of bones, assembles itself without the addition of noncollagenous proteins or their polymeric substitutes. Rheological experiments demonstrated that the stiffness of gels derived from these fibrils is enhanced by mineralization. Growth experiments of human adipose derived stem cells on these gels showed the compatibility of the fibrils in a tissue-regeneration context.
View details for DOI 10.1021/nl200116d
View details for Web of Science ID 000288061500082
View details for PubMedID 21280646
View details for PubMedCentralID PMC3053435
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Particle sorting using a porous membrane in a microfluidic device
LAB ON A CHIP
2011; 11 (2): 238-245
Abstract
Porous membranes have been fabricated based on the development of the perforated membrane mold [Y. Luo and R. N. Zare, Lab Chip, 2008, 8, 1688-1694] to create a single filter that contains multiple pore sizes ranging from 6.4 to 16.6 µm inside a monolithic three-dimensional poly(dimethylsiloxane) microfluidic structure. By overlapping two filters we are able to achieve smaller pore size openings (2.5 to 3.3 µm). This filter operates without any detectable irreversible clogging, which is achieved using a cross-flow placed in front of each filtration section. The utility of a particle-sorting device that contains this filter is demonstrated by separating polystyrene beads of different diameters with an efficiency greater than 99.9%. Additionally, we demonstrate the effectiveness of this particle-sorting device by separating whole blood samples into white blood cells and red blood cells with platelets.
View details for DOI 10.1039/c0lc00121j
View details for Web of Science ID 000285514700007
View details for PubMedID 21057685
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Why Help a Growing Scientific Giant?
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2011; 50 (36): 8202-8203
View details for DOI 10.1002/anie.201105242
View details for Web of Science ID 000295259700001
View details for PubMedID 23210135
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Microfluidic purification and analysis of hematopoietic stem cells from bone marrow
LAB ON A CHIP
2011; 11 (18): 3130-3135
Abstract
Hematopoietic stem cells are larger in size than other cells present in bone marrow, with the exception of monocytes. This distinguishing characteristic can be used to separate them from a whole-marrow sample. A microfluidic device was fabricated using an integrated membrane that is porous at defined areas. This allows for simultaneous valving and filtering functionality, which is crucial for preventing irreversible clogging. This device, as well as a separation procedure, was optimized in this work to enrich hematopoietic progenitor cells from diluted bone marrow of leukemia patients without any additional sample preparation. An enrichment of up to 98% was achieved with this method and the process was scaled up to 17.2 μL min(-1) of processed sample. Additionally, stem cells were stained with specific antibodies for further analysis. Using a custom-made computer program, the filter was scanned to characterize and quantify cells based on fluorescence. The results were evaluated by comparing them against the results obtained from flow cytometry, confocal microscopy, and Coulter counting.
View details for DOI 10.1039/c1lc20353c
View details for Web of Science ID 000294263400013
View details for PubMedID 21799976
- Detecting Reaction Intermediates in Liquids on the Millisecond Time Scale Using Desorption Electrospray Ionization Angew. Chemie Int. Ed. 2011; 50: 250-254
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Control and imaging of O(D-1(2)) precession
NATURE CHEMISTRY
2011; 3 (1): 28-33
Abstract
Larmor precession of a quantum mechanical angular momentum vector about an applied magnetic field forms the basis for a range of magnetic resonance techniques, including nuclear magnetic resonance spectroscopy and magnetic resonance imaging. We have used a polarized laser pump-probe scheme with velocity-map imaging detection to visualize, for the first time, the precessional motion of a quantum mechanical angular momentum vector. Photodissociation of O(2) at 157 nm provides a clean source of fast-moving O((1)D(2)) atoms, with their electronic angular momentum vector strongly aligned perpendicular to the recoil direction. In the presence of an external magnetic field, the distribution of atomic angular momenta precesses about the field direction, and polarization-sensitive images of the atomic scattering distribution recorded as a function of field strength yield 'time-lapse-photography' style movies of the precessional motion. We present movies recorded in various experimental geometries, and discuss potential consequences and applications in atmospheric chemistry and reaction dynamics.
View details for DOI 10.1038/NCHEM.929
View details for Web of Science ID 000285336900012
View details for PubMedID 21160513
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Generation of Melamine Polymer Condensates upon Hypergolic Ignition of Dicyanamide Ionic Liquids
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2011; 50 (37): 8634-8637
View details for DOI 10.1002/anie.201101247
View details for Web of Science ID 000295261200034
View details for PubMedID 21786369
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Differential cross sections for H + D-2 -> HD(v '=2, j '=0,3,6,9) + D at center-of-mass collision energies of 1.25, 1.61, and 1.97 eV
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
2011; 13 (18): 8175-8179
Abstract
We have measured differential cross sections (DCSs) for the reaction H + D(2) → HD(v' = 2,j' = 0,3,6,9) + D at center-of-mass collision energies E(coll) of 1.25, 1.61, and 1.97 eV using the photoloc technique. The DCSs show a strong dependence on the product rotational quantum number. For the HD(v' = 2,j' = 0) product, the DCS is bimodal but becomes oscillatory as the collision energy is increased. For the other product states, they are dominated by a single peak, which shifts from back to sideward scattering as j' increases, and they are in general less sensitive to changes in the collision energy. The experimental results are compared to quantum mechanical calculations and show good, but not fully quantitative agreement.
View details for DOI 10.1039/c0cp02460k
View details for Web of Science ID 000289954300012
View details for PubMedID 21170442
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Detecting Reaction Intermediates in Liquids on the Millisecond Time Scale Using Desorption Electrospray Ionization
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2011; 50 (1): 250-254
View details for DOI 10.1002/anie.201004861
View details for Web of Science ID 000285891900019
View details for PubMedID 21110361
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Stopped-Flow Kinetic Analysis Using Hadamard Transform Time-of-Flight Mass Spectrometry
ANALYTICAL CHEMISTRY
2010; 82 (20): 8650-8657
Abstract
A home-built stopped-flow apparatus is interfaced to a Hadamard transform time-of-flight mass spectrometer, which permits study of reaction kinetics with a time between reaction initiation and observation as short as about 100 ms and a sampling rate of chemical change that can approach 1 ms. This technique is applied to the trypsin-catalyzed hydrolysis of several peptides and is validated by comparing the results with literature values as well as to optical data obtained with the present stopped-flow apparatus. In addition, we report a kinetic study of the action of trypsin on a peptide having more than one cleavage site.
View details for DOI 10.1021/ac101899n
View details for Web of Science ID 000282859100040
View details for PubMedID 20843011
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Biodegradable Nanoparticles With Sustained Release of Functional siRNA in Skin
JOURNAL OF PHARMACEUTICAL SCIENCES
2010; 99 (10): 4261-4266
Abstract
A key challenge in developing RNAi-based therapeutics is efficient delivery of functional short interfering RNA (siRNA) to target cells. To address this need, we have used a supercritical CO(2) process to incorporate siRNA in biodegradable polymer nanoparticles (NPs) for in vivo sustained release. By this means we have obtained complete encapsulation of the siRNA with minimal initial burst effect from the surface of the NPs. The slow release of a fluorescently labeled siRNA mimic (siGLO Red) was observed for up to 80 days in vivo after intradermal injection into mouse footpads. In vivo gene silencing experiments were also performed, showing reduction of GFP signal in the epidermis of a reporter transgenic mouse model, which demonstrates that the siRNA retained activity following release from the polymer NPs.
View details for DOI 10.1002/jps.22147
View details for Web of Science ID 000282473400012
View details for PubMedID 20737633
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Polycyclic aromatic hydrocarbons in asteroid 2008 TC3: Dispersion of organic compounds inside asteroids
METEORITICS & PLANETARY SCIENCE
2010; 45 (10-11): 1710-1717
View details for DOI 10.1111/j.1945-5100.2010.01103.x
View details for Web of Science ID 000285759700009
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Polarization of molecular targets using infrared stimulated Raman adiabatic passage
JOURNAL OF CHEMICAL PHYSICS
2010; 133 (9)
Abstract
We suggest that infrared stimulated Raman adiabatic passage, a coherent multiple excitation process, can be used to create a superposition of (2J+1) highly correlated M-state sublevels of a rigid rotor molecule with vibrational level v and rotational level J. This method employs the (v=0,J-2) to (v=2,J) S-branch transition, which is carried out in a counterintuitive manner in which the v=1 to v=2 transition is pumped prior to the v=0 to v=1 transition, causing nearly complete population transfer to the v=2 final level. We use perpendicular and parallel linearly polarized infrared excitation (biaxial excitation). Specifically, the perpendicular polarization connects the v=1 intermediate level to the final vibrational level v=2, and the parallel polarization connects the initial level v=0 to the intermediate level v=1. By this means we break the cylindrical symmetry for an ensemble of vibrationally excited molecules in a rovibrational eigenstate (v=2,J). The angular momentum polarization is determined by the relative phases rather than by the populations of the magnetic M-sublevels. For the phase correlated ensemble, the angular momentum polarization can be considered as a purely quantum mechanical effect. Using a fully general density matrix treatment, we illustrate this approach by considering a beam of carbon monoxide (CO) molecules. We find that significant polarization for J=2, 5, and 10 can be achieved with a cw infrared laser source having modest power (∼100 mW/mm(2)). We believe that this technique is a general one and may offer an experimentally accessible new platform for different applications, from scattering studies with M-state entangled ensembles of molecules to logic gate operations of a quantum computer.
View details for DOI 10.1063/1.3475523
View details for Web of Science ID 000281742900007
View details for PubMedID 20831312
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Characterization of asphaltenes and petroleum by mass spectrometry
AMER CHEMICAL SOC. 2010
View details for Web of Science ID 000208164703047
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Comparing Laser Desorption/Laser Ionization Mass Spectra of Asphaltenes and Model Compounds
ENERGY & FUELS
2010; 24: 3589-3594
View details for DOI 10.1021/ef100402g
View details for Web of Science ID 000278851200041
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General Method for Producing Organic Nanoparticles Using Nanoporous Membranes
NANO LETTERS
2010; 10 (6): 2202-2206
Abstract
Two liquids are separated by a nanoporous membrane and one liquid is made to flow into the other, causing nanoparticles to be formed at the exits of the nanopores. In particular, we report the generation of nanoparticles of the biodegradable polysaccharide polymer chitosan by placing the chitosan in a low pH aqueous solution that is flowed into a high pH aqueous solution. The size of the nanoparticles (5-20 nm) can be roughly controlled by choosing the size of the nanopores and the pumping rate. In addition, it is possible to load the chitosan nanoparticles with drug molecules, which is demonstrated by incorporation of up to 3.3% rhodamine 6G molecules in the chitosan nanoparticles.
View details for DOI 10.1021/nl101057d
View details for Web of Science ID 000278449200039
View details for PubMedID 20441186
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Nanoparticle Formation of Organic Compounds With Retained Biological Activity
JOURNAL OF PHARMACEUTICAL SCIENCES
2010; 99 (6): 2750-2755
Abstract
Many pharmaceuticals are formulated as powders to aid drug delivery. A major problem is how to produce powders having high purity, controlled morphology, and retained bioactivity. We demonstrate the use of supercritical carbon dioxide as an antisolvent for meeting this need for two model drug systems, quercetin, a sparingly soluble antioxidant, and short interfering RNA (siRNA), which can silence genes. In both cases we achieve retention of bioactivity as well as a narrow particle size distribution in which the particles are free of impurities.
View details for DOI 10.1002/jps.22035
View details for Web of Science ID 000278241800022
View details for PubMedID 20039390
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Preparation of polarized molecules using coherent infrared multicolor ladder excitation
JOURNAL OF CHEMICAL PHYSICS
2010; 132 (15)
Abstract
A density matrix treatment is presented for a general process of preparing polarized molecules through their coherent interaction with two or more infrared photons of different frequencies, each tuned to cause a transition between real levels. This process, which might be called infrared stimulated Raman adiabatic passage, allows complete population transfer to selected rotational-vibrational levels and controls the direction of the rotational angular momentum vector J of the molecule with the possibility of preparing higher moments of the J spatial distribution. HCl molecules in a supersonic molecular beam are considered as a candidate system. Theory predicts that under collision-free conditions two infrared laser pulses of microsecond duration and milliwatt power are able to achieve complete population transfer and alignment of HCl (v=2, J=2, and M=0) for mutually parallel excitation and HCl (v=2, J=2, and M=+/-1) for mutually perpendicular excitation. Orientation of the HCl (v=2, J=2, and M=+/-2) can also be achieved using two circularly polarized pulses of the same helicity. For simplicity, our treatment ignores nuclear spin depolarization, which would be the case for molecules such as (12)C(16)O and (12)C(16)OO(2). Polarized molecules in higher vibrational levels can be prepared using additional infrared pulses.
View details for DOI 10.1063/1.3352553
View details for Web of Science ID 000276971500016
View details for PubMedID 20423176
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Assessment and control of organic and other contaminants associated with the Stardust sample return from comet 81P/Wild 2
METEORITICS & PLANETARY SCIENCE
2010; 45 (3): 406-433
View details for DOI 10.1111/j.1945-5100.2010.01031.x
View details for Web of Science ID 000279904700006
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Search for Br* production in the D plus DBr reaction
JOURNAL OF CHEMICAL PHYSICS
2010; 132 (8)
Abstract
Deuterium bromide (DBr) is expanded from a pulsed jet into a vacuum and a synchronized pulsed laser causes photodissociation of some of the DBr molecules to produce primarily (approximately 85%) ground-state bromine atoms ((2)P(3/2)) and fast D atoms. The latter collide with the cold DBr molecules and react to produce molecular deuterium (D(2)) via two possible channels, the adiabatic channel D(2)+Br((2)P(3/2)) and the nonadiabatic channel D(2)+Br*((2)P(1/2)), which are asymptotically separated in energy by the spin-orbit splitting (0.457 eV) of the bromine atom. Ion images are recorded for D(2)(v'=1, J'=16, 18-21), D(2)(v'=2, J'=6,7, 10-12, 14-16), and D(2)(v'=3, J'=2-5) for various collision energies. For the nonadiabatic production of spin-orbit-excited Br* in the D+DBr reaction for the conditions studied we estimate that this channel contributes 1% or less.
View details for DOI 10.1063/1.3319717
View details for Web of Science ID 000275029200016
View details for PubMedID 20192296
- Search for Br* Production in the D + DBr Reaction J. Chem. Phys. 2010; 132: 084301-1-7
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Capture & Release of Single Cells on a Microfluidic Chip Via Conical Nanopores
CELL PRESS. 2010: 194A
View details for DOI 10.1016/j.bpj.2009.12.1032
View details for Web of Science ID 000208762001478
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Amplification & Analysis of the Synechococcus Os-B' Crispr Region from Single Cells
CELL PRESS. 2010: 406A
View details for DOI 10.1016/j.bpj.2009.12.2188
View details for Web of Science ID 000208762004022
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SINGLE-MOLECULE SPECTROSCOPY USING MICROFLUIDIC PLATFORMS
METHODS IN ENZYMOLOGY, VOL 472: SINGLE MOLECULE TOOLS, PT A: FLUORESCENCE BASED APPROACHES
2010; 472: 119-132
Abstract
Microfluidics serves as a convenient platform for single-molecule experiments by providing manipulation of small amounts of liquids and micron-sized particles. An adapted version of capillary electrophoresis (CE) on a microchip can be utilized to separate chemical species with high resolution based on their ionic mobilities (i.e., charges and sizes), but identification of separated species is not trivial, especially for complex mixtures of sticky biomolecules. We describe here how to use a surfactant mixture system for CE on a poly(dimethylsiloxane) (PDMS) microchip, capture separated peaks within a 50-pl chamber using microvalves, analyze the fluorescence signals with correlation spectroscopy to extract molecular diffusion characteristics, and to identify the biomolecular clusters in a model immunocomplex system.
View details for DOI 10.1016/S0076-6879(10)72013-9
View details for Web of Science ID 000279058600007
View details for PubMedID 20580962
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Sustained release of nucleic acids from polymeric nanoparticles using microemulsion precipitation in supercritical carbon dioxide
CHEMICAL COMMUNICATIONS
2010; 46 (47): 9034-9036
Abstract
A general approach for producing biodegradable nanoparticles for sustained nucleic acid release is presented. The nanoparticles are produced by precipitating a water-in-oil microemulsion in supercritical CO(2). The microemulsion consists of a transfer RNA aqueous solution (water phase), dichloromethane containing poly(l-lactic acid)-poly(ethylene glycol) (oil phase), the surfactant n-octyl β-D-glucopyranoside, and the cosurfactant n-butanol.
View details for DOI 10.1039/c0cc04258g
View details for Web of Science ID 000284482100040
View details for PubMedID 21052588
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Microfluidic Platforms for Single-Cell Analysis
ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 12
2010; 12: 187-201
Abstract
Microfluidics, the study and control of the fluidic behavior in microstructures, has emerged as an important enabling tool for single-cell chemical analysis. The complex procedures for chemical cytometry experiments can be integrated into a single microfabricated device. The capability of handling a volume of liquid as small as picoliters can be utilized to manipulate cells, perform controlled cell lysis and chemical reactions, and efficiently minimize sample dilution after lysis. The separation modalities such as chromatography and electrophoresis within microchannels are incorporated to analyze various types of intracellular components quantitatively. The microfluidic approach offers a rapid, accurate, and cost-effective tool for single-cell biology. We present an overview of the recent developments in microfluidic technology for chemical-content analysis of individual cells.
View details for DOI 10.1146/annurev-bioeng-070909-105238
View details for Web of Science ID 000281447400008
View details for PubMedID 20433347
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Time-dependent depolarization of aligned D-2 caused by hyperfine coupling
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
2010; 12 (48): 15689-15694
Abstract
Molecular deuterium is prepared in the J = 2, M = 0 sublevel of ν = 1 by stimulated Raman pumping of the ν = 0 S(0) line. Following optical excitation, the degree of alignment of the rotational angular momentum J oscillates in time caused by the coupling of J to the total nuclear spin angular momentum I(T). This coupling is of two kinds, the interaction of J with the magnetic moments and the quadrupole fields of the two I = 1 deuterium nuclei. The alignment is monitored via the O(2) line of the E,F(1)Σ(g)(+)-X(1)Σ(g)(+) (0,1) band using [2+1] resonance enhanced multiphoton ionization for pump-probe delays from 0 to 20 μs. Using the hyperfine coupling constants found previously for the ν = 0 state (R. F. Code and N. F. Ramsey, Phys. Rev. A, 1971, 4, 1945), we are able to fit the time dependence essentially within our experimental error, but this requires that the presence of both I(T) = 0 and I(T) = 2 nuclear spin states for this o-deuterium level is properly weighted and taken into account.
View details for DOI 10.1039/c0cp00518e
View details for Web of Science ID 000284776700015
View details for PubMedID 20668756
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Desorption Electrospray Ionization: Achieving Rapid Sampling Rates
ANALYTICAL CHEMISTRY
2009; 81 (21): 9035-9040
Abstract
The sampling rate and imaging capabilities of desorption electrospray ionization (DESI) are examined using a rotating sample platform combined with Hadamard transform time-of-flight mass spectrometry (HTTOFMS), a multiplexed time-of-flight technique that allows for millisecond acquisition of full mass-to-charge ratio scans. DESI-compatible dyes are used to produce spatially defined sample patterns on poly(methyl methacrylate) discs. Control of disk rotation rate sets the residence time of the sample spots in the DESI plume, and thus the sampling rate. Surface patterns of alternating analytes are spectrally resolved up to 80 samples/s and single-analyte spots up to 50 samples/s. The rapid movement of the surface under the DESI plume allows for high DESI solution flow rates without blurring the chemical information on the surface. Data from multiple rotations can be additively combined, generating a chemical image of the surface with improved signal-to-noise characteristics. This multipass data enables analysis of the rising and falling edges of the analyte signal, placing a lower limit on both the temporal resolution of DESI and the maximum achievable sampling rate. Multipass analysis is proposed as a method for DESI surface imaging.
View details for DOI 10.1021/ac901668a
View details for Web of Science ID 000276191900054
View details for PubMedID 19778033
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The Power of the Question
RESONANCE-JOURNAL OF SCIENCE EDUCATION
2009; 14 (8): 818-819
View details for DOI 10.1007/s12045-009-0077-6
View details for Web of Science ID 000421484200009
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High-precision optical measurements of C-13/C-12 isotope ratios in organic compounds at natural abundance
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2009; 106 (27): 10928-10932
Abstract
A continuous-flow cavity ring-down spectroscopy (CRDS) system integrating a chromatographic separation technique, a catalytic combustor, and an isotopic (13)C/(12)C optical analyzer is described for the isotopic analysis of a mixture of organic compounds. A demonstration of its potential is made for the geochemically important class of short-chain hydrocarbons. The system proved to be linear over a 3-fold injection volume dynamic range with an average precision of 0.95 per thousand and 0.67 per thousand for ethane and propane, respectively. The calibrated accuracy for methane, ethane, and propane is within 3 per thousand of the values determined using isotope ratio mass spectrometry (IRMS), which is the current method of choice for compound-specific isotope analysis. With anticipated improvements, the low-cost, portable, and easy-to-use CRDS-based instrumental setup is poised to evolve into a credible challenge to the high-cost and complex IRMS-based technique.
View details for DOI 10.1073/pnas.0904230106
View details for Web of Science ID 000267796100013
View details for PubMedID 19564619
View details for PubMedCentralID PMC2708708
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Ultraviolet thermal lensing detection of amino acids
32nd International Symposium on High Performance Liquid Phase Separations and Related Techniques
ELSEVIER SCIENCE BV. 2009: 3423–30
Abstract
Thermal lensing (TL) permits ultra-sensitive measurements of optical absorption of analytes in very small liquid volumes. We report the construction and use of a TL detector based on pulsed ultraviolet (UV) laser excitation (266 nm). We applied this detector to quantitate amino acids using capillary electrophoresis (CE) as a means of separation. Sixteen individual amino acids are readily detected, but the signal has a complex dependence on intensity caused by the combination of (1) one-photon absorption; (2) two-photon absorption (TPA); and (3) photodestruction of amino acid molecules in the focus of the laser beam. An aqueous solution containing tyrosine, tryptophan, and cysteine is electrophoretically separated and the individual amino acids are detected by UV TL. The estimated limit of detection is 7 microM for tyrosine, 2.5 microM for tryptophan and 33 microM for cysterine, which translates into 0.35 fmol for tyrosine, 0.125 fmol for tryptophan, and 1.65 fmol for cysteine in the 140pL detection volume. It is found that two-photon absorption of water and the formation of color centers in the fused silica walls of the flowcell can contribute a significant, drifting background signal, but this interference can be minimized by selecting an appropriate focus condition and excitation-detection geometry. We suggest that as UV laser sources become available, UV TL may become a method of choice for measuring the concentrations of many analytes in different separation formats in which the volume is highly limited.
View details for DOI 10.1016/j.chroma.2008.05.096
View details for Web of Science ID 000265262300002
View details for PubMedID 18589430
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Asphaltene Molecular-Mass Distribution Determined by Two-Step Laser Mass Spectrometry
9th International Conference on Petroleum Phase Behavior and Fouling
AMER CHEMICAL SOC. 2009: 1162–1168
View details for DOI 10.1021/ef8006239
View details for Web of Science ID 000265439000005
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Phenotypic and Genotypic Heterogeneity of Cyanobacterial Populations in Hot Spring Microbial Mats Revealed by Microfluidic Single-Cell Analysis
CELL PRESS. 2009: 50A
View details for Web of Science ID 000426275900253
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No More Pencils, No More Books 2008 George C. Pimentel Award, Sponsored by Rohm and Haas Co.
JOURNAL OF CHEMICAL EDUCATION
2009; 86 (2): 142-144
View details for DOI 10.1021/ed086p142
View details for Web of Science ID 000262718400002
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Charting a Course for Chemistry Education
JOURNAL OF CHEMICAL EDUCATION
2009; 86 (2): 145
View details for Web of Science ID 000262718400003
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A Microfluidic Platform for the Culture & Analysis of Single Cells
CELL PRESS. 2009: 49A
View details for Web of Science ID 000426275900247
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Organic compound alteration during hypervelocity collection of carbonaceous materials in aerogel
METEORITICS & PLANETARY SCIENCE
2009; 44 (1): 15-24
View details for Web of Science ID 000264476300002
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Time-dependent depolarization of aligned HD molecules
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
2009; 11 (1): 142-147
Abstract
An aligned sample of HD(v = 1, J = 2, M(J) = 0) molecules is prepared under collision-free conditions using the S(0) stimulated Raman pumping transition. Subsequent coupling to the spins of the deuteron I(D) and the proton I(H) causes the initial degree of alignment to oscillate and decrease as monitored over the time range from 0-13 mus via the O2 line of the [2 + 1] REMPI E,F(1)Sigma-X(1)Sigma (0,1) band. The time dependence of the rotational alignment is also calculated using both a hierarchical coupling scheme in which the rotational angular momentum J is regarded first to couple to I(D), and then the resultant F(i) to couple to I(H), to form the total angular momentum F and a non-hierarchical coupling scheme in which the HD energy level structure is not assumed to be diagonal in the |I(H)(JI(D))F(i)FM(F)> basis set. The experimental data is in good agreement with the non-hierarchical calculation but not with the hierarchical calculation, as expected for this system. Additionally, we calculate the time dependence of the H and D nuclear spin polarizations.
View details for DOI 10.1039/b814133a
View details for PubMedID 19081917
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Laser mass spectrometric detection of extraterrestrial aromatic molecules: Mini-review and examination of pulsed heating effects
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2008; 105 (47): 18096-18101
Abstract
Laser mass spectrometry is a powerful tool for the sensitive, selective, and spatially resolved analysis of organic compounds in extraterrestrial materials. Using microprobe two-step laser mass spectrometry (muL(2)MS), we have explored the organic composition of many different exogenous materials, including meteorites, interplanetary dust particles, and interstellar ice analogs, gaining significant insight into the nature of extraterrestrial materials. Recently, we applied muL(2)MS to analyze the effect of heating caused by hypervelocity particle capture in aerogel, which was used on the NASA Stardust Mission to capture comet particles. We show that this material exhibits complex organic molecules upon sudden heating. Similar pulsed heating of carbonaceous materials is shown to produce an artifactual fullerene signal. We review the use of muL(2)MS to investigate extraterrestrial materials, and we discuss its recent application to characterize the effect of pulsed heating on samples of interest.
View details for DOI 10.1073/pnas.0801860105
View details for Web of Science ID 000261489300014
View details for PubMedID 18687897
View details for PubMedCentralID PMC2587552
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Vibrationally inelastic H + D-2 collisions are forward-scattered
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2008; 105 (47): 18194-18199
Abstract
We have measured differential cross sections (DCSs) for the vibrationally inelastic scattering process H + o-D(2)(v = 0, j = 0,2) --> H + o-D(2)(v' = 1-4, j' even). Several different collision energies and nearly the entire range of populated product quantum states are studied. The products are dominantly forward-scattered in all cases. This behavior is the opposite of what is predicted by the conventional textbook mechanism, in which collisions at small impact parameters compress the bond and cause the products to recoil in the backward direction. Recent quasiclassical trajectory (QCT) calculations examining only the o-D(2)(v' = 3, j') products suggest that vibrationally inelastic scattering is the result of a frustrated reaction in which the D-D bond is stretched, but not broken, during the collision. These QCT calculations provide a qualitative explanation for the observed forward-scattering, but they do not agree with experiments at the lowest values of j'. The present work shows that quantum mechanical calculations agree closely with experiments and expands upon previous results to show that forward-scattering is universally observed in vibrationally inelastic H + D(2) collisions over a broad range of conditions.
View details for DOI 10.1073/pnas.0807942105
View details for Web of Science ID 000261489300030
View details for PubMedID 19015513
View details for PubMedCentralID PMC2587579
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Identifying the source of a strong fullerene envelope arising from laser desorption mass spectrometric analysis of meteoritic insoluble organic matter
GEOCHIMICA ET COSMOCHIMICA ACTA
2008; 72 (22): 5521-5529
View details for DOI 10.1016/j.gca.2008.08.008
View details for Web of Science ID 000260562900012
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Continuous Time-of-Flight Ion Imaging: Application to Fragmentation
ANALYTICAL CHEMISTRY
2008; 80 (21): 8299-8307
Abstract
We have designed and constructed a continuous imaging reflectron time-of-flight mass spectrometer (TOFMS) that provides a mass spectrum at every pixel of a two-dimensional image with a 100% duty cycle. The technique is based on pseudorandom ion beam modulation and three-dimensional ( x, y, t) ion imaging. We use a multichannel plate detector with a delay-line anode that provides x, y positions and flight times t of every ion arrival event. The precision of the peak heights in the 100% duty cycle mass spectra is shown to be enhanced even at short (10 ms) acquisition times, which should prove useful for the study of solution kinetics or fast chromatographic separations. As a demonstration of the system's capability, we have imaged the fragmented ions that underwent surface-induced dissociation inside the reflectron and the ions that fragmented spontaneously through postsource decay.
View details for DOI 10.1021/ac801512n
View details for Web of Science ID 000260567000055
View details for PubMedID 18837560
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On the quantum and quasiclassical angular distributions of photofragments
JOURNAL OF CHEMICAL PHYSICS
2008; 129 (16)
Abstract
Quantum and quasiclassical expressions for the angular distribution of photofragments from an initially polarized precursor molecule are compared under the conditions of a one-photon electric dipole transition to a repulsive state followed by prompt axial recoil into two separating fragments. The treatment is most readily applicable to diatomic molecules, but it is more general than that. It is shown that when the rotational and electronic angular momentum J(i) and its projection along the body-fixed z axis Omega(i) are well defined in the initial state, the quantum and quasiclassical expressions are identical for any initial polarization of the molecule prior to photolysis and for all values of J(i) and Omega(i). For the particular case of an mid R:J(i)Omega(i)M(i) selected state this is in agreement with a previous result [T. Seideman, Chem. Phys. Lett. 253, 279 (1996)]. Moreover, the quasiclassical expression is still a good approximation even when the initial state is a coherent superposition of mid R:J(i),Omega(i),M(i) levels for the same Omega(i). This near identity still pertains even when Omega(i) is not well defined for a parallel transition (DeltaOmega=0) but fails for a perpendicular transition (DeltaOmega=+/-1) if the initial state is in a coherent superposition of Omega(i) states differing by +/-2. These conclusions apply to preparation schemes employing optical excitation, static inhomogeneous and/or homogeneous electric and/or magnetic fields, as well as to molecules physisorbed on solids or clusters. We discuss the importance of these results in the interpretation of photofragment distributions when some other angular momenta are involved, such as electronic angular momentum, with and without nuclear spin, coupled to molecular rotation, asymmetric top rotational angular momentum, or internal vibrational angular momentum in polyatomics.
View details for DOI 10.1063/1.3000581
View details for Web of Science ID 000260572300037
View details for PubMedID 19045274
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Corroboration of theory for H+D-2 -> D+HD (v '=3, j '=0) reactive scattering dynamics
JOURNAL OF PHYSICAL CHEMISTRY A
2008; 112 (39): 9266-9268
Abstract
The differential cross section (DCS) for the reaction H + D2 --> D + HD (v' = 3, j' = 0) exhibits particularly rich dynamics; in addition to the expected direct recoil backscattering feature, a surprising time-delayed forward scattering feature appears that has been attributed to glory scattering arising from nearside and farside interference. This fact leads to a complex DCS that depends strongly on the collision energy. Its accurate calculation requires a fully quantum mechanical (QM) treatment. We report improved measurements of this DCS over the collision energy range 1.55 < or = E(coll) < or = 1.82 eV. Previous measurements using the core extraction method, while generally in agreement with theory, lacked sufficient resolution to capture all of the noteworthy behavior of the system; in the present work, we use ion imaging to observe many previously unresolved features of the DCS, particularly in the forward-scattered region. Agreement with QM calculations is found at all collision energies, reconciling an earlier discrepancy between experiment and theory near E(coll) = 1.54 eV.
View details for DOI 10.1021/jp801187p
View details for PubMedID 18435532
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Perforated membrane method for fabricating three-dimensional polydimethylsiloxane microfluidic devices
LAB ON A CHIP
2008; 8 (10): 1688-1694
Abstract
A procedure is described for making layer-to-layer interconnections in polydimethylsiloxane (PDMS) microfluidic devices. Thin (approximately 50 microm) perforated PDMS membranes are bonded to thicker (0.1 cm or more) PDMS slabs by means of thermally cured PDMS prepolymer to form a three-dimensional (3D) channel structure, which may contain channel or valve arrays that can pass over and under one another. Devices containing as many as two slabs and three perforated membranes are demonstrated. We also present 3D PDMS microfluidic devices for display and for liquid dispensing.
View details for DOI 10.1039/b807751g
View details for Web of Science ID 000260466300013
View details for PubMedID 18813392
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Preparation of oriented and aligned H-2 and HD by stimulated Raman pumping
JOURNAL OF CHEMICAL PHYSICS
2008; 129 (8)
Abstract
Stimulated Raman pumping has been used to prepare oriented and aligned samples of H(2)(nu=1,J=1,2,3) and HD(nu=1,J=2) under collision-free conditions using the (1,0) S(0), S(1), Q(1), Q(2), and O(3) lines. The M-sublevel anisotropies were interrogated by polarized [2+1] resonance-enhanced multiphoton ionization via the (0,1) O(2), O(3), and S(1) lines of the E,F (1)Sigma(g) (+)-X (1)Sigma(g) (+) system. The optical excitation schemes employed in this study generate highly oriented and aligned molecular ensembles. We show that the H(2)(nu=1,J=2,M=0) and H(2)(nu=1,J=2,M=2) samples retain their initial polarization for greater than 100 ns and are therefore suitable candidates for targets or projectiles in future scattering experiments.
View details for DOI 10.1063/1.2973628
View details for PubMedID 19044828
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Folding control and unfolding free energy of yeast iso-1-cytochrome c bound to layered zirconium phosphate materials monitored by surface plasmon resonance
JOURNAL OF PHYSICAL CHEMISTRY B
2008; 112 (30): 9201-9208
Abstract
The free energy change (Delta G degrees ) for the unfolding of immobilized yeast iso-1-cytochrome c (Cyt c) at nanoassemblies was measured by surface plasmon resonance (SPR) spectroscopy. Data show that SPR is sensitive to protein conformational changes, and protein solid interface exerts a major influence on bound protein stability. First, Cyt c was self-assembled on the Au film via the single thiol of Cys-102. Then, crystalline sheets of layered alpha-Zr(O(3)POH)(2).H(2)O (alpha-ZrP) or Zr(O(3)PCH(2)CH(2)COOH)(2).xH(2)O (alpha-ZrCEP) were adsorbed to construct alpha-ZrP/Cyt c/Au or alpha-ZrCEP/Cyt c/Au nanoassemblies. The construction of each layer was monitored by SPR, in real time, and the assemblies were further characterized by atomic force microscopy and electrochemical studies. Thermodynamic stability of the protein nanoassembly was assessed by urea-induced unfolding. Surprisingly, unfolding is reversible in all cases studied here. Stability of Cyt c in alpha-ZrP/Cyt c/Au increased by approximately 4.3 kJ/mol when compared to the unfolding free energy of Cyt c/Au assembly. In contrast, the protein stability decreased by approximately 1.5 kJ/mol for alpha-ZrCEP/Cyt c/Au layer. Thus, OH-decorated surfaces stabilized the protein whereas COOH-decorated surfaces destabilized it. These data quantitate the role of specific functional groups of the inorganic layers in controlling bound protein stability.
View details for DOI 10.1021/jp7121642
View details for Web of Science ID 000257926800048
View details for PubMedID 18598069
View details for PubMedCentralID PMC3490220
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Capture of phosphopeptides using alpha-zirconium phosphate nanoplatelets
ANALYTICAL CHEMISTRY
2008; 80 (14): 5542-5549
Abstract
Alpha-zirconium phosphate nanoplatelets (alpha-ZrPN) were studied as a binding agent for phosphopeptides. Nanoplatelets of alpha-zirconium phosphate were incubated overnight with zirconium oxychloride, followed by centrifugation, and washed twice with water followed by an aqueous solution of 80% acetonitrile to form the binding agent. Alpha-ZrPN were able specifically to capture phosphoserine-containing peptides from a tryptic digest of a complex peptide mixture in which its abundance was only 0.05%. Alpha-ZrPN also bound peptides containing phosphothreonine and phosphotyrosine. The limit of detection for phosphopeptides is approximately 2 fmol, based on using matrix-assisted laser desorption/ionization mass spectrometry. Alpha-ZrPN were applied for the analysis of tryptic digests of mouse liver and leukemia cell phosphoproteomes and succeeded in identifying 158 phosphopeptides (209 phosphorylation sites) from 101 phosphoproteins in mouse liver lysate and 78 phosphopeptides (104 phosphorylation sites) from 59 phosphoproteins in leukemia cell extract. For these two tryptic digests, the alpha-ZrPN approach is able to capture more phosphopeptides than that obtained from TiO2 particles or from Fe(3+)-IMAC beads, but each method is able to bind some phosphopeptides that the others do not.
View details for DOI 10.1021/ac800577z
View details for Web of Science ID 000257598100036
View details for PubMedID 18522436
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The power of the question
CHEMICAL & ENGINEERING NEWS
2008; 86 (28): 3
View details for DOI 10.1021/cen-v086n028.p003
View details for Web of Science ID 000257735900001
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Vibrational excitation through tug-of-war inelastic collisions
NATURE
2008; 454 (7200): 88-91
Abstract
Vibrationally inelastic scattering is a fundamental collision process that converts some of the kinetic energy of the colliding partners into vibrational excitation(,). The conventional wisdom is that collisions with high impact parameters (where the partners only 'graze' each other) are forward scattered and essentially elastic, whereas collisions with low impact parameters transfer a large amount of energy into vibrations and are mainly back scattered. Here we report experimental observations of exactly the opposite behaviour for the simplest and most studied of all neutral-neutral collisions: we find that the inelastic scattering process H + D(2)(v = 0, j = 0, 2) --> H + D(2)(v' = 3, j' = 0, 2, 4, 6, 8) leads dominantly to forward scattering (v and j respectively refer to the vibrational and rotational quantum numbers of the D(2) molecule). Quasi-classical trajectory calculations show that the vibrational excitation is caused by extension, not compression, of the D-D bond through interaction with the passing H atom. However, the H-D interaction never becomes strong enough for capture of the H atom before it departs with diminished kinetic energy; that is, the inelastic scattering process is essentially a frustrated reaction in which the collision typically excites the outward-going half of the H-D-D symmetric stretch before the H-D(2) complex dissociates. We suggest that this 'tug of war' between H and D(2) is a new mechanism for vibrational excitation that should play a role in all neutral-neutral collisions where strong attraction can develop between the collision partners.
View details for DOI 10.1038/nature07079
View details for Web of Science ID 000257308300042
View details for PubMedID 18596807
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Two-step laser mass spectrometry of asphaltenes
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2008; 130 (23): 7216-?
Abstract
Defined by their solubility in toluene and insolubility in n-heptane, asphaltenes are a highly aromatic, polydisperse mixture consisting of the heaviest and most polar fraction of crude oil. Although asphaltenes are critically important to the exploitation of conventional oil and are poised to rise in significance along with the exploitation of heavy oil, even as fundamental a quantity as their molecular weight distribution is unknown to within an order of magnitude. Laser desorption/ionization (LDI) mass spectra vary greatly with experimental parameters so are difficult to interpret: some groups favor high laser pulse energy measurements (yielding heavy molecular weights), arguing that high pulse energy is required to detect the heaviest components of this mixture; other groups favor low pulse energy measurements (yielding light molecular weights), arguing that low pulse energy is required to avoid aggregation in the plasma plume. Here we report asphaltene mass spectra recorded with two-step laser mass spectrometry (L2MS), in which desorption and ionization are decoupled and no plasma is produced. L2MS mass spectra of asphaltenes are insensitive to laser pulse energy and other parameters, demonstrating that the asphaltene molecular weight distribution can be measured without limitation from insufficient laser pulse energy or plasma-phase aggregation. These data resolve the controversy from LDI, showing that the asphaltene molecular weight distribution peaks near 600 Da and previous measurements reporting much heavier species suffered from aggregation effects.
View details for DOI 10.1021/ja801927v
View details for Web of Science ID 000256550600025
View details for PubMedID 18484722
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Computer-controlled, variable-frequency power supply for driving multipole ion guides
REVIEW OF SCIENTIFIC INSTRUMENTS
2008; 79 (3)
Abstract
A high voltage, variable-frequency driver circuit for powering resonant multipole ion guides is presented. Two key features of this design are (1) the use of integrated circuits in the driver stage and (2) the use a stepper motor for tuning a large variable capacitor in the resonant stage. In the present configuration the available frequency range spans a factor of 2. The actual values of the minimum and maximum frequencies depend on the chosen inductor and the capacitance of the ion guide. Feedback allows for stabilized, computer-adjustable rf amplitudes over the range of 5-500 V. The rf power supply was characterized over the range of 350-750 kHz and evaluated by driving a quadrupole ion guide in an electrospray time-of-flight mass spectrometer.
View details for DOI 10.1063/1.2884148
View details for Web of Science ID 000254538100047
View details for PubMedID 18377035
- Vibrationally Inelastic H+D2 Collisions Are Forward Scattered Proc. Natl. Acad. Sci. USA 2008: 18194–18199
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Questions to Chemical Educators from the Chemistry Community
NUTS AND BOLTS OF CHEMICAL EDUCATION RESEARCH
2008; 976: 11-18
View details for Web of Science ID 000277624800002
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CaSSS award
JOURNAL OF SEPARATION SCIENCE
2008; 31 (1): 207-208
View details for Web of Science ID 000252861700028
- Questions to Chemical Educations from the Chemistry Community Nuts and Bolts of Chemical Education Research edited by Bunce, D. M., Cole, R. S. Oxford, UK: Oxford University Press. 2008: 11–18
- Afterword Chemical Evolution Across Space and Time: From the Big Bang to Prebiotic Chemistry edited by Zaikowski, L., Friedrich, J. M. 2008: 389–90
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Microfluidic device for immunoassays based on surface plasmon resonance imaging
LAB ON A CHIP
2008; 8 (5): 694-700
Abstract
We have designed and fabricated a polydimethylsiloxane (PDMS) microfluidic device containing an array of gold spots onto which antigens or antibodies of interest can be attached. We use surface plasmon resonance (SPR) imaging to monitor the antibody-antigen recognition and binding events. This combination offers two significant advantages: (1) the microfluidic device dramatically reduces reaction time and sample consumption; and (2) the SPR imaging yields real-time detection of the immunocomplex formation. Thus, an immunoreaction may be detected and quantitatively characterized in about 10 min. The sensitivity of this method is at the subnanomolar level. When gold nanoparticles are selectively coupled to the immunocomplex to cause signal amplification, the sensitivity reaches the ten to one hundred picomolar level but the time required increases to about 60 min.
View details for DOI 10.1039/b800606g
View details for Web of Science ID 000255276700009
View details for PubMedID 18432338
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Surface plasmon resonance study of vesicle rupture by virus-mimetic attack
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
2008; 10 (22): 3203-3208
Abstract
Frank and coworkers [N. J. Cho, S. J. Cho, K. H. Cheong, J. S. Glenn and C. W. Frank, J. Am. Chem. Soc., 2007, 129, 10050] investigated what happens when lipid vesicles made of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), which serves as a mimic for cell membranes, are exposed to the amphipathic helix peptide, PEP1, which is of the same type found in hepatitis C virus. Using atomic force field microscopy and quartz crystal microbalance measurements they presented evidence that the vesicle is transformed into a lipid bilayer. We use surface plasmon resonance (SPR) microscopy to follow this process in real time. We find an induction period (intermediate state) of approximately 10-min duration between the time of membrane binding and membrane rupture. The SPR data support the interpretation that a lipid bilayer is formed and allow us to put forward a mechanism for the vesicle-rupture event. As a side benefit, we demonstrate how to build two-dimensional lipid patterns on a gold surface using this vesicle-rupture process.
View details for DOI 10.1039/b802632g
View details for Web of Science ID 000256114700003
View details for PubMedID 18500396
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Sustained release of drugs dispersed in polymer nanoparticles
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2008; 47 (41): 7880-7882
View details for DOI 10.1002/anie.200802260
View details for Web of Science ID 000260062500019
View details for PubMedID 18773393
View details for PubMedCentralID PMC2586612
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Micromachined Bradbury-Nielsen gates
ANALYTICAL CHEMISTRY
2007; 79 (23): 9160-9165
Abstract
Bradbury-Nielsen gates (BNGs) are a standard way for gating or steering beams of charged particles in ion mobility spectrometry and time-of-flight mass spectrometry. They consist of a pair of interleaved electrodes that when at the same potential allow ions to pass through the electrodes undeflected and, when a voltage is applied, cause the ions to be deflected from their propagation axis. Previous efforts to construct such devices have relied on mechanical assembly by winding wires across an aperture. We describe a micromachining method for making monolithic BNGs using deep reactive ion etching of silicon-on-insulator wafers. This method enables the creation of electrodes with spacings ranging from 25 to 100 microm with a thickness of 20 microm, covering a 5 mm by 5 mm active area. We characterize the performance of these micromachined BNGs by ion imaging in a pseudorandom time-of-flight mass spectrometer.
View details for DOI 10.1021/ac071581e
View details for Web of Science ID 000251311900049
View details for PubMedID 17966990
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Use of a mixture of n-dodecyl-beta-D-maltoside and sodium dodecyl sulfate in poly(dimethylsiloxane) microchips to suppress adhesion and promote separation of proteins
ANALYTICAL CHEMISTRY
2007; 79 (23): 9145-9149
Abstract
Dynamic modification of poly(dimethylsiloxane) channels using a mixture of n-dodecyl-beta-D-maltoside (DDM) and sodium dodecyl sulfate (SDS) is able to suppress analyte adsorption and control electroosmotic flow (EOF). In this mixed surfactant system, the nonionic surfactant DDM functions as a surface blocking reagent, whereas the anionic surfactant SDS introduces negative charges to the channel walls. Changing the DDM/SDS mixing ratio tunes the surface charge density and the strength of EOF. Using 0.1% (w/v) DDM and 0.03% (w/v) SDS, Alexa Fluor 647 labeled streptavidin can be analyzed according to the charges added by the fluorophores. Protein molecules with different numbers of fluorophores are well resolved. DDM and SDS also form negatively charged mixed micelles, which act as a separation medium. The low critical micellar concentration of DDM/SDS mixed micelles also allows the use of SDS at a nondenaturing concentration, which enables the analysis of proteins in their native state. The immunocomplex between a membrane protein, beta2 adrenergic receptor, and anti-FLAG antibody has been fully separated using 0.1% (w/v) DDM and 0.03% (w/v) SDS. We have also analyzed the composition of light-harvesting protein-chromophore complexes in cyanobacteria.
View details for DOI 10.1021/ac071544n
View details for Web of Science ID 000251311900047
View details for PubMedID 17948969
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Visible light-induced photopolymerization of an in situ macroporous sol-gel monolith
JOURNAL OF SEPARATION SCIENCE
2007; 30 (17): 2979-2985
Abstract
A one-step, in situ, photopolymerization of a mixture of methacryloxypropyltrimethoxysilane in the presence of an acid catalyst, water, and toluene is accomplished in a 75 microm id polyimide-coated capillary using visible light (460 nm) for a 15 min irradiation time. The mixture is a two-component photosystem comprising Irgacure 784 photosensitizer and diphenyliodonium chloride photoinitiator. The visible photopolymerized sol-gel (vis-PSG) column shows RP chromatographic behavior. The analytical potential of these columns is demonstrated with the isocratic separation of small, neutral alkyl phenyl ketones. Operational parameters, such as mobile phase composition, field strength, and column temperature were varied to assess how they affect the separation performance of the monolith.
View details for DOI 10.1002/jssc.200700328
View details for Web of Science ID 000251461500024
View details for PubMedID 17960846
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Simple template-based method to produce Bradbury-Nielsen gates
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
2007; 18 (11): 1901-1908
Abstract
A Bradbury-Nielsen gate (BNG) consists of two interleaved and electrically isolated sets of wires and can transmit or deflect charged particles by applying a varying voltage difference across the two wire sets. We present a simple template-based method to fabricate BNGs with wire spacings as small as 50 microm with minimal use of a microscope. The small wire spacing allows modulation rates at tens of megahertz. Using this method, we have fabricated four BNGs with wire spacings of 500, 200, 100, and 50 microm using 10 microm gold-coated tungsten wires. The performance of the four BNGs is characterized using an imaging detector and compared with theoretical predictions.
View details for DOI 10.1016/j.jasms.2007.07.030
View details for Web of Science ID 000250844900001
View details for PubMedID 17827033
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Optical control of ground-state atomic orbital alignment: Cl(2P3/2) atoms from HCl(v=2,J=1) photodissociation.
journal of chemical physics
2007; 127 (14): 144307-?
Abstract
H(35)Cl(v=0,J=0) molecules in a supersonic expansion were excited to the H(35)Cl(v=2,J=1,M=0) state with linearly polarized laser pulses at about 1.7 microm. These rotationally aligned J=1 molecules were then selectively photodissociated with a linearly polarized laser pulse at 220 nm after a time delay, and the velocity-dependent alignment of the (35)Cl((2)P(32)) photofragments was measured using 2+1 REMPI and time-of-flight mass spectrometry. The (35)Cl((2)P(32)) atoms are aligned by two mechanisms: (1) the time-dependent transfer of rotational polarization of the H(35)Cl(v=2,J=1,M=0) molecule to the (35)Cl((2)P(32)) nuclear spin [which is conserved during the photodissociation and thus contributes to the total (35)Cl((2)P(32)) photofragment atomic polarization] and (2) the alignment of the (35)Cl((2)P(32)) electronic polarization resulting from the photoexcitation and dissociation process. The total alignment of the (35)Cl((2)P(32)) photofragments from these two mechanisms was found to vary as a function of time delay between the excitation and the photolysis laser pulses, in agreement with theoretical predictions. We show that the alignment of the ground-state (35)Cl((2)P(32)) atoms, with respect to the photodissociation recoil direction, can be controlled optically. Potential applications include the study of alignment-dependent collision effects.
View details for PubMedID 17935395
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Optical control of ground-state atomic orbital alignment: Cl(P-2(3/2)) atoms from HCl(v=2,J=1) photodissociation
JOURNAL OF CHEMICAL PHYSICS
2007; 127 (14)
Abstract
H(35)Cl(v=0,J=0) molecules in a supersonic expansion were excited to the H(35)Cl(v=2,J=1,M=0) state with linearly polarized laser pulses at about 1.7 microm. These rotationally aligned J=1 molecules were then selectively photodissociated with a linearly polarized laser pulse at 220 nm after a time delay, and the velocity-dependent alignment of the (35)Cl((2)P(32)) photofragments was measured using 2+1 REMPI and time-of-flight mass spectrometry. The (35)Cl((2)P(32)) atoms are aligned by two mechanisms: (1) the time-dependent transfer of rotational polarization of the H(35)Cl(v=2,J=1,M=0) molecule to the (35)Cl((2)P(32)) nuclear spin [which is conserved during the photodissociation and thus contributes to the total (35)Cl((2)P(32)) photofragment atomic polarization] and (2) the alignment of the (35)Cl((2)P(32)) electronic polarization resulting from the photoexcitation and dissociation process. The total alignment of the (35)Cl((2)P(32)) photofragments from these two mechanisms was found to vary as a function of time delay between the excitation and the photolysis laser pulses, in agreement with theoretical predictions. We show that the alignment of the ground-state (35)Cl((2)P(32)) atoms, with respect to the photodissociation recoil direction, can be controlled optically. Potential applications include the study of alignment-dependent collision effects.
View details for DOI 10.1063/1.2772272
View details for Web of Science ID 000250140800021
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Differential cross section for the H+D-2 -> HD(v '=1,j '=2,6,10)+D reaction as a function of collision energy
JOURNAL OF CHEMICAL PHYSICS
2007; 127 (12)
Abstract
We have measured differential cross sections (DCSs) for the HD (v(')=1,j(')=2,6,10) products of the H+D(2) exchange reaction at five different collision energies in the range 1.48< or =E(coll)< or =1.94 eV. The contribution from the less energetic H atoms formed upon spin-orbit excitation of Br in the photolysis of the HBr precursor is taken into account for two collision energies, E(coll)=1.84 and 1.94 eV, allowing us to disentangle the two different channels. The measured DCSs agree well with new time-dependent quantum-mechanical calculations. As the product rotational excitation increases, the DCSs shift from backward to sideward scattering, as expected. We also find that the shapes of the DCSs show only a small overall dependence on the collision energy, with a notable exception occurring for HD (v(')=1,j(')=2), which appears bimodal at high collision energies. We suggest that this feature results from both direct recoil and indirect scattering from the conical intersection.
View details for DOI 10.1063/1.2771157
View details for Web of Science ID 000249787300027
View details for PubMedID 17902911
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Comment on "Organics captured from Comet 81P/Wild 2 by the Stardust spacecraft"
SCIENCE
2007; 317 (5845)
Abstract
Sandford et al. (Reports, 15 December 2006, p. 1720) reported on organic compounds captured from Comet 81P/Wild 2 by the Stardust spacecraft. We emphasize the difficulty in assigning the origin of compounds detected diffusely along particle impact tracks and show that rapid heating of aerogel that has never been exposed to cometary particle capture can generate complex aromatic molecules from low-mass carbon impurities present in the aerogel.
View details for DOI 10.1126/science.1142407
View details for PubMedID 17885115
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Comment on "Organics captured from Comet 81P/Wild 2 by the Stardust spacecraft"
SCIENCE
2007; 317 (5845)
View details for DOI 10.1126/science.1142407
View details for Web of Science ID 000249585900021
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Detection of separated analytes in subnanoliter volumes using coaxial thermal lensing
ANALYTICAL CHEMISTRY
2007; 79 (14): 5264-5271
Abstract
A collinear-beam thermal lens detector has been constructed and its properties were characterized. Its application to the high-performance liquid chromatography (HPLC) separation of a mixture of five anthraquinone dyes dissolved in water shows a linear response over 3.5 orders of magnitude and a detection limit that is subnanomolar in the dye concentrations. These results are compared with those obtained previously using cavity ring-down spectroscopy (CRDS) in a Brewster's angle flow cell (Bechtel, K. L.; Zare, R. N.; Kachanov, A. A.; Sanders, S. S.; Paldus, B. A. Anal. Chem. 2005, 77, 1177-1182). The peak-to-peak baseline noise of the thermal lensing detection is 3.5 x 10(-8) absorbance units (AU) with a path length of 200 microm, whereas the peak-to-peak baseline noise of CRDS detection is approximately 2 x 10(-7) AU with a path length of 300 microm. Both of these figures of merit should be compared to the peak-to-peak baseline noise of one of the best commercial UV-vis HPLC detection systems, which is approximately 5 x 10(-6) AU with a path length of 10 mm (1-s integration time). Therefore, the thermal lensing technique has a demonstrated sensitivity of subnanomolar detection that is approximately 140 times better than that of the best commercial UV-vis detector and approximately 5 times better than that of CRDS.
View details for DOI 10.1021/ac0705925
View details for Web of Science ID 000247992600021
View details for PubMedID 17569503
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Preparation of highly polarized nuclei: Observation and control of time-dependent polarization transfer from (HCl)-Cl-35 molecular rotation to Cl-35 nuclear spin
PHYSICAL REVIEW A
2007; 76 (1)
View details for DOI 10.1103/PhysRevA.76.012503
View details for Web of Science ID 000248486600078
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Characterization of two types of silanol groups on fused-silica surfaces using evanescent-wave cavity ring-down spectroscopy
ANALYTICAL CHEMISTRY
2007; 79 (10): 3654-3661
Abstract
Evanescent-wave cavity ring-down spectroscopy has been applied to a planar fused-silica surface covered with crystal violet (CV+) cations to characterize the silanol groups indirectly. A radiation-polarization dependence of the adsorption isotherm of CV+ at the CH3CN/silica interface is measured and fit to a two-site Langmuir equation to determine the relative populations of two different types of isolated silanol groups. CV+ binding at type I sites yields a free energy of adsorption of -29.9 +/- 0.2 kJ/mol and a saturation surface density of (7.4 +/- 0.5) x 10(12) cm(-2), whereas the values of -17.9 +/- 0.4 kJ/mol and (3.1 +/- 0.4) x 10(13) cm(-2) are obtained for the type II sites. The CV+ cations, each with a planar area of approximately 120 A2, seem to be aligned randomly while lying over the SiO- type I sites, thereby suggesting that this type of site may be surrounded by a large empty surface area (>480 A2). In contrast, the CV+ cations on a type II sites are restricted with an average angle of approximately 40 degrees tilted off the surface normal, suggesting that the CV+ cations on these sites are grouped closely together. The average tilt angle increases with increasing concentration of crystal violet so that CV+ cations may be separated from each other to minimize the repulsion of nearby CV+ and SiOH sites.
View details for DOI 10.1021/ac062386n
View details for Web of Science ID 000246414400017
View details for PubMedID 17429945
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Structure and conformational changes in the C-terminal domain of the beta(2)-adrenoceptor - Insights from fluorescence resonance energy transfer studies
JOURNAL OF BIOLOGICAL CHEMISTRY
2007; 282 (18): 13895-13905
Abstract
The C terminus of the beta(2)-adrenoceptor (AR) interacts with G protein-coupled receptor kinases and arrestins in an agonist-dependent manner, suggesting that conformational changes induced by ligands in the transmembrane domains are transmitted to the C terminus. We used fluorescence resonance energy transfer (FRET) to examine ligand-induced structural changes in the distance between two positions on the beta(2)-AR C terminus and cysteine 265 (Cys-265) at the cytoplasmic end of transmembrane domain 6. The donor fluorophore FlAsH (Fluorescein Arsenical Helix binder) was attached to a CCPGCC motif introduced at position 351-356 in the proximal C terminus or at the distal C terminus. An acceptor fluorophore, Alexa Fluor 568, was attached to Cys-265. FRET analyses revealed that the average distances between Cys-265 and the proximal and distal FlAsH sites were 57 and 62A(,) respectively. These relatively large distances suggest that the C terminus is in an extended, relatively unstructured conformation. Nevertheless, we observed ligand-specific changes in FRET. All ligands induced an increase in FRET between the proximal C-terminal FlAsH site and Cys-265. Ligands that have been shown to induce arrestin-dependent ERK activation, including the catecholamine agonists and the inverse agonist ICI118551, led to a decrease in FRET between the distal FlAsH site and Cys-265, whereas other ligands had no effect or induced a small increase in FRET. Taken together the results provide new insight into the structure of the C terminus of the beta(2)-AR as well as ligand-induced conformational changes that may be relevant to arrestin-dependent regulation and signaling.
View details for DOI 10.1074/jbc.M611904200
View details for Web of Science ID 000246060300079
View details for PubMedID 17347144
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A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2007; 104 (18): 7682-7687
Abstract
G protein-coupled receptors (GPCRs) respond to a diverse array of ligands, mediating cellular responses to hormones and neurotransmitters, as well as the senses of smell and taste. The structures of the GPCR rhodopsin and several G proteins have been determined by x-ray crystallography, yet the organization of the signaling complex between GPCRs and G proteins is poorly understood. The observations that some GPCRs are obligate heterodimers, and that many GPCRs form both homo- and heterodimers, has led to speculation that GPCR dimers may be required for efficient activation of G proteins. However, technical limitations have precluded a definitive analysis of G protein coupling to monomeric GPCRs in a biochemically defined and membrane-bound system. Here we demonstrate that a prototypical GPCR, the beta2-adrenergic receptor (beta2AR), can be incorporated into a reconstituted high-density lipoprotein (rHDL) phospholipid bilayer particle together with the stimulatory heterotrimeric G protein, Gs. Single-molecule fluorescence imaging and FRET analysis demonstrate that a single beta2AR is incorporated per rHDL particle. The monomeric beta2AR efficiently activates Gs and displays GTP-sensitive allosteric ligand-binding properties. These data suggest that a monomeric receptor in a lipid bilayer is the minimal functional unit necessary for signaling, and that the cooperativity of agonist binding is due to G protein association with a receptor monomer and not receptor oligomerization.
View details for DOI 10.1073/pnas.0611448104
View details for Web of Science ID 000246239400068
View details for PubMedID 17452637
View details for PubMedCentralID PMC1863461
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Surface plasmon resonance imaging using a high numerical aperture microscope objective
ANALYTICAL CHEMISTRY
2007; 79 (7): 2979-2983
Abstract
We designed, constructed, and tested a surface plasmon resonance (SPR) microscope using a high numerical aperture objective from a commercially available inverted optical microscope. Such a configuration, combined with various methods to shorten the surface plasmon propagation length, achieves diffraction-limited spatial resolution in the transverse direction and near-diffraction-limited resolution in the longitudinal direction. A virtue of the objective-type SPR imaging is that we achieve distortion-free angle-resolved SPR imaging, allowing the angle-dependent reflectivity of the sample to be examined on a pixel-by-pixel basis, thus offering high-resolution information about surface properties.
View details for DOI 10.1021/ac062284x
View details for Web of Science ID 000245304300046
View details for PubMedID 17309232
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Reaction of Cl with CD4 excited to the second C-D stretching overtone
JOURNAL OF CHEMICAL PHYSICS
2007; 126 (4)
Abstract
The effects of vibrational excitation on the Cl+CD(4) reaction are investigated by preparing three nearly isoenergetic vibrational states: mid R:3000 at 6279.66 cm(-1), |2100> at 6534.20 cm(-1), and |1110> at 6764.24 cm(-1), where |D(1)D(2)D(3)D(4)> identifies the number of vibrational quanta in each C-D oscillator. Vibrational excitation of the perdeuteromethane is via direct infrared pumping. The reaction is initiated by photolysis of molecular chlorine at 355 nm. The nascent methyl radical product distribution is measured by 2+1 resonance-enhanced multiphoton ionization at 330 nm. The resulting CD(3) state distributions reveal a preference to remove all energy available in the most excited C-D oscillator. Although the energetics are nearly identical, the authors observe strong mode specificity in which the CD(3) state distributions markedly differ between the three Cl-atom reactions. Reaction with CD(4) prepared in the |3000> mode leads to CD(3) products populated primarily in the ground state, reaction with CD(4) prepared in the |2100> mode leads primarily to CD(3) with one quantum of stretch excitation, and reaction with CD(4) prepared in the |1110> mode leads primarily to CD(3) with one quantum of C-D stretch excitation in two oscillators. There are some minor deviations from this behavior, most notably that the Cl atom is able to abstract more energy than is available in a single C-D oscillator, as in the case of |2100>, wherein a small population of ground-state CD(3) is observed. These exceptions likely result from the mixings between different second overtone stretch combination bands. They also measure isotropic and anisotropic time-of-flight profiles of CD(3) (nu(1)=1,2) products from the Cl+CD(4) |2100> reaction, providing speed distributions, spatial anisotropies, and differential cross sections that indicate that energy introduced as vibrational energy into the system essentially remains as such throughout the course of the reaction.
View details for DOI 10.1063/1.2431368
View details for PubMedID 17286478
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Doppler-free ion imaging of hydrogen molecules produced in bimolecular reactions
CHEMICAL PHYSICS LETTERS
2007; 433 (4-6): 439-443
View details for DOI 10.1016/j.cplett.2006.11.073
View details for Web of Science ID 000243900700035
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Counting low-copy number proteins in a single cell
SCIENCE
2007; 315 (5808): 81-84
Abstract
We have designed a microfluidic device in which we can manipulate, lyse, label, separate, and quantify the protein contents of a single cell using single-molecule fluorescence counting. Generic labeling of proteins is achieved through fluorescent-antibody binding. The use of cylindrical optics enables high-efficiency (approximately 60%) counting of molecules in micrometer-sized channels. We used this microfluidic device to quantify beta2 adrenergic receptors expressed in insect cells (SF9). We also analyzed phycobiliprotein contents in individual cyanobacterial cells (Synechococcus sp. PCC 7942) and observed marked differences in the levels of specific complexes in cell populations that were grown under nitrogen-depleted conditions.
View details for DOI 10.1126/science.1133992
View details for Web of Science ID 000243259100039
View details for PubMedID 17204646
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Microfluidic separation and capture of analytes for single-molecule spectroscopy
LAB ON A CHIP
2007; 7 (12): 1663-1665
Abstract
A complex mixture of fluorescently labeled biological molecules is separated electrophoretically on a chip and the constituent molecules are confined in a sub-nanolitre microchamber, which allows analysis by various single-molecule techniques.
View details for DOI 10.1039/b713103h
View details for Web of Science ID 000251121000013
View details for PubMedID 18030384
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Foreword by the guest editors
ISRAEL JOURNAL OF CHEMISTRY
2007; 47 (1): I-VI
View details for Web of Science ID 000254385000001
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Collaborative Research: The Good, the Bad, and the Beautiful
230th National Meeting of the American-Chemical-Society
AMER CHEMICAL SOC. 2007: 259–270
View details for Web of Science ID 000270493500019
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Organics captured from comet 81P/Wild 2 by the Stardust spacecraft
SCIENCE
2006; 314 (5806): 1720-1724
Abstract
Organics found in comet 81P/Wild 2 samples show a heterogeneous and unequilibrated distribution in abundance and composition. Some organics are similar, but not identical, to those in interplanetary dust particles and carbonaceous meteorites. A class of aromatic-poor organic material is also present. The organics are rich in oxygen and nitrogen compared with meteoritic organics. Aromatic compounds are present, but the samples tend to be relatively poorer in aromatics than are meteorites and interplanetary dust particles. The presence of deuterium and nitrogen-15 excesses suggest that some organics have an interstellar/protostellar heritage. Although the variable extent of modification of these materials by impact capture is not yet fully constrained, a diverse suite of organic compounds is present and identifiable within the returned samples.
View details for DOI 10.1126/science.1135841
View details for Web of Science ID 000242833600043
View details for PubMedID 17170291
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Research article - Comet 81P/Wild 2 under a microscope
SCIENCE
2006; 314 (5806): 1711-1716
Abstract
The Stardust spacecraft collected thousands of particles from comet 81P/Wild 2 and returned them to Earth for laboratory study. The preliminary examination of these samples shows that the nonvolatile portion of the comet is an unequilibrated assortment of materials that have both presolar and solar system origin. The comet contains an abundance of silicate grains that are much larger than predictions of interstellar grain models, and many of these are high-temperature minerals that appear to have formed in the inner regions of the solar nebula. Their presence in a comet proves that the formation of the solar system included mixing on the grandest scales.
View details for DOI 10.1126/science.1135840
View details for Web of Science ID 000242833600041
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Comet 81P/Wild 2 under a microscope.
Science
2006; 314 (5806): 1711-1716
Abstract
The Stardust spacecraft collected thousands of particles from comet 81P/Wild 2 and returned them to Earth for laboratory study. The preliminary examination of these samples shows that the nonvolatile portion of the comet is an unequilibrated assortment of materials that have both presolar and solar system origin. The comet contains an abundance of silicate grains that are much larger than predictions of interstellar grain models, and many of these are high-temperature minerals that appear to have formed in the inner regions of the solar nebula. Their presence in a comet proves that the formation of the solar system included mixing on the grandest scales.
View details for PubMedID 17170289
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Construction and calibration of an instrument for three-dimensional ion imaging
JOURNAL OF CHEMICAL PHYSICS
2006; 125 (13)
Abstract
We describe a new instrument based on a delay-line detector for imaging the complete three-dimensional velocity distribution of photoionized products from photoinitiated reactions. Doppler-free [2+1] resonantly enhanced multiphoton ionization (REMPI) of H and D atoms formed upon photolysis of HBr and DBr in the range 203 nm < or = lambda photolysis < or = 243 nm yields radial speeds measured to be accurate within 1% of those calculated. The relative speed resolution is about 5% and limited by photoionization recoil broadening. A relative speed resolution of 3.4% is obtained for [3+1] REMPI, which minimizes the ionization recoil. We also determine the branching ratio between ground-state and spin-orbit-excited product channels and their associated anisotropies. We find that DBr photolysis dynamics differs slightly from its HBr counterpart.
View details for DOI 10.1063/1.2217742
View details for Web of Science ID 000241056600069
View details for PubMedID 17029486
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On-line biological sample cleanup for electrospray mass spectrometry using sol-gel columns
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
2006; 842 (1): 70-74
Abstract
Using a slight overpressure, a urine sample is loaded onto a monolithic photopolymerized sol-gel column that has been derivatized with hydrophobic carbon chains and then the complex urine matrix is washed with aqueous solution. A buffer containing organic solvent is used to elute the adsorbed peptides by an applied voltage and the sample is then introduced into a mass spectrometer by sheath flow electrospray. The importance of desalting this type of sample is demonstrated by an experiment that shows that the signal intensity of a test solution with neurotensin, sprayed directly into the mass spectrometer, decreased from 4.5x10(4) cps to no detectible signal when just 10% urine is added to the sample solution. We suggest that this procedure may find general application for desalting biological samples prior to mass spectrometric analysis.
View details for DOI 10.1016/j.jchromb.2006.05.012
View details for Web of Science ID 000240712700011
View details for PubMedID 16814621
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Controlling electroosmotic flow in poly(dimethylsiloxane) separation channels by means of prepolymer additives
ANALYTICAL CHEMISTRY
2006; 78 (13): 4588-4592
Abstract
The electroosmotic flow (EOF) in a poly(dimethylsiloxane) (PDMS) separation channel can be altered and controlled by adding a carboxylic acid to the prepolymer prior to curing. When the prepolymer is doped with 0.5 wt % undecylenic acid (UDA), the electroosmotic mobility in a modified PDMS channel rises to (7.6 +/- 0.2) x 10(-4) cm(2) V(-1) s(-1) (in HEPES buffer at pH 8.5), which is nearly twice that in the native PDMS channel. Because this modification does not significantly change the hydrophobicity of the PDMS surface, it is possible to combine the modified PDMS with a dynamic coating of n-dodecyl beta-d-maltoside (DDM), which prevents protein sticking (see Huang, B.; Wu, H. K.; Kim, S.; Zare, R. N. Lab Chip 2005, 5, 1005-1007). The modified PDMS channel with a dynamic coating of DDM generates an electroosmotic mobility of (5.01 +/- 0.09) x 10(-4) cm(2) V(-1) s(-1), which shows excellent reproducibility both in successive runs and during storage in water. Combining this surface modification and the dynamic coating of DDM is an effective means for both providing stable EOF in the PDMS channels and preventing protein adsorption on the channel walls. To demonstrate these effects, we show that the electrophoretic separation of immunocomplexes in free solution can be readily accomplished in a microfluidic chip made of UDA-doped (0.5 wt %) PDMS with a dynamic coating of DDM.
View details for DOI 10.1021/ac052274g
View details for Web of Science ID 000238665200047
View details for PubMedID 16808469
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Perspective - Sex, lies, and Title IX
CHEMICAL & ENGINEERING NEWS
2006; 84 (20): 46-?
View details for Web of Science ID 000237585400048
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UV photolysis of quinoline in interstellar ice analogs
METEORITICS & PLANETARY SCIENCE
2006; 41 (5): 785-796
View details for Web of Science ID 000237674000011
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Generation of complex, static solution gradients in microfluidic channels
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2006; 128 (13): 4194-4195
Abstract
A microfluidic device is used to generate a complex gradient of diffusible molecules in a static solution. The gradient is precise and steady both in space and in time. This device, made from poly(dimethylsiloxane), consists of three layers. The molecules in reservoirs on the top layer diffuse through the flat middle layer of hydrogel and reach an equilibrium distribution. Microfluidic channels on the bottom layer that are in close contact with the hydrogel contain free solution that has concentration gradients based on the gradient in the gel. The gradient profile in the channel can be designed to have an arbitrary form (within the range of the existing gradient in the hydrogel) by controlling the local direction of the channel at each point.
View details for DOI 10.1021/ja058530o
View details for Web of Science ID 000236518300015
View details for PubMedID 16568971
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The power of a failed demonstration: Water electrolysis
AMER CHEMICAL SOC. 2006
View details for Web of Science ID 000238125901280
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Chemistry - Resonances in reaction dynamics
SCIENCE
2006; 311 (5766): 1383-1385
View details for DOI 10.1126/science.1124421
View details for Web of Science ID 000236029400024
View details for PubMedID 16527958
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H+CD4 abstraction reaction dynamics: Product energy partitioning
JOURNAL OF PHYSICAL CHEMISTRY A
2006; 110 (9): 3017-3027
Abstract
This paper presents experimental and theoretical studies of the product energy partitioning associated with the H + CD4 (nu = 0) --> HD + CD3 reaction for the collision energy range 0.5-3.0 eV. The theoretical results are based on quasiclassical trajectories from (1) first principles direct dynamics calculations (B3LYP/6-31G), (2) an empirical surface developed by Espinosa-García [J. Chem. Phys. 2002, 116, 10664] (EG), and (3) two semiempirical surfaces (MSINDO and reparametrized MSINDO). We find that most of the energy appears in product translation at energies just above the reactive threshold; however, HD vibration and rotation become quite important at energies above 1 eV, each accounting for over 20% of the available energy above 1.5 eV, according to the B3LYP calculations. The barrier on the B3LYP surface, though being later than that on EG, predicts significantly higher HD vibrational excitation than EG. This deviation is contradictory to what would be expected on the basis of the Polanyi rules and derives from modest differences in the potential energy surfaces. The CD3 internal energy is generally quite low, and we present detailed rotational state distributions which show that the CD3 rotational distribution is largely independent of collision energy in the 0.75-1.95 eV range. The most populated rotational levels are N = 5 and 6 on B3LYP, with most of that excitation being associated with motion about the C2 axes, rather than C3 axis, of the CD3 product, in good agreement with the experimental results. Through our extensive studies in this and previous work concerning the scattering dynamics, we conclude that B3LYP/6-31G provides the best available description of the overall dynamics for the title reaction at relatively high collision energies.
View details for DOI 10.1021/jp055017o
View details for Web of Science ID 000235944000021
View details for PubMedID 16509623
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Phospholipid biotinylation of polydimethylsiloxane (PDMS) for protein immobilization
LAB ON A CHIP
2006; 6 (3): 369-373
Abstract
Polydimethylsiloxane (PDMS) surfaces can be functionalized with biotin groups by adding biotinylated phospholipids to the PDMS prepolymer before curing. The addition of beta-D-dodecyl-N-maltoside (DDM) in the solution blocks non-specific protein binding on these functionalized PDMS surfaces. We characterize the surface by measuring fluorescently labeled streptavidin binding. Single molecule tracking shows that the phospholipids are not covalently linked to PDMS polymer chains, but the surface functionalization is not removed by washing. We demonstrate the immobilization of biotinylated antibodies and lectins through biotin-avidin interactions.
View details for DOI 10.1039/b515840k
View details for Web of Science ID 000235993800005
View details for PubMedID 16511619
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Tribute to Professor S. Terabe
JOURNAL OF CHROMATOGRAPHY A
2006; 1106 (1-2): 4-4
View details for DOI 10.1016/j.chroma.2005.10.079
View details for Web of Science ID 000235256800003
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Comparing reactions of H and Cl with C-H stretch-excited CHD3
JOURNAL OF CHEMICAL PHYSICS
2006; 124 (3)
Abstract
We report the methyl radical product state distributions for the reactions of H and Cl with CHD3(nu1 = 1,2) at collision energies of 1.53 and 0.18 eV, respectively. Both reactions demonstrate mode selectivity. The resulting state distributions from the H+CHD3(nu1 = 1,2) reactions are well described by a spectator model. The reactions Cl + CHD3(nu1 = 1,2) exhibit similar behavior, but in some aspects the spectator model breaks down. We attribute this breakdown to enhanced intramolecular vibrational redistribution in the Cl + CHD3(nu1 = 1,2) reactions compared to the H + CHD3(nu1 = 1,2) reactions, caused by the interaction of the slower Cl atom with the vibrationally excited CHD3, which is promoted either by its longer collision duration, its stronger coupling, or both.
View details for DOI 10.1063/1.2155434
View details for Web of Science ID 000234757400028
View details for PubMedID 16438587
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H+CD4 abstraction reaction dynamics: Excitation function and angular distributions
JOURNAL OF PHYSICAL CHEMISTRY A
2006; 110 (2): 677-686
Abstract
We compare experimental photoloc measurements and quasi-classical trajectory calculations of the integral cross sections, lab-frame speed distributions, and angular distributions associated with the CD3 products of the H + CD4(nu = 0) --> CD3 + HD reaction at collision energies ranging from 0.5 to 3.0 eV. Of the potential energy surfaces (PES) we explored, the direct dynamics calculations using the B3LYP/6-31G** density functional theory PES provide the best agreement with the experimental measurements. This agreement is likely due to the better overall description that B3LYP provides for geometries well removed from the minimum energy path, even though its barrier height is low by approximately 0.2 eV. In contrast to previous theoretical calculations, the angular distributions on this surface show behavior associated with a stripping mechanism, even at collision energies only approximately 0.1 eV above the reaction barrier. Other potential energy surfaces, which include an analytical potential energy surface from Espinosa-García and a direct dynamics calculation based on the MSINDO semiempirical Hamiltonian, are less accurate and predict more rebound dynamics at these energies than is observed. Reparametrization of the MSINDO surface, though yielding better agreement with the experiment, is not sufficient to capture the observed dynamics. The differences between these surfaces are interpreted using an analysis of the opacity functions, where we find that the wider cone of acceptance on the B3LYP surface plays a crucial role in determining the integral cross sections and angular distributions.
View details for DOI 10.1021/jp053827u
View details for Web of Science ID 000234699000036
View details for PubMedID 16405340
- Cl + CH4 Reaction Dynamics Vector Correlation and Alignment in Chemistry edited by Balint-Kurti, G. G., de Miranda, M. P. Daresbury Laboratory, Daresbury, UK. 2006
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Cytochrome c conformations resolved by the photon counting histogram: Watching the alkaline transition with single-molecule sensitivity
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2005; 102 (49): 17570-17575
Abstract
We apply the photon counting histogram (PCH) model, a fluorescence technique with single-molecule sensitivity, to study pH-induced conformational changes of cytochrome c. PCH is able to distinguish different protein conformations based on the brightness of a fluorophore sensitive to its local environment. We label cytochrome c through its single free cysteine with tetramethylrhodamine-5-maleimide (TMR), a fluorophore with specific brightnesses that we associate with specific protein conformations. Ensemble measurements demonstrate two different fluorescence responses with increasing pH: (i) a decrease in fluorescence intensity caused by the alkaline transition of cytochrome c (pH 7.0-9.5), and (ii) an increase in intensity when the protein unfolds (pH 9.5-10.8). The magnitudes of these two responses depend strongly on the molar ratio of TMR used to label cytochrome c. Using PCH we determine that this effect arises from the proportion of a nonfunctional conformation in the sample, which can be differentiated from the functional conformation. We further determine the causes of each ensemble fluorescence response: (i) during the alkaline transition, the fluorophore enters a dark state and discrete conformations are observed, and (ii) as cytochrome c unfolds, the fluorophore incrementally brightens, but discrete conformations are no longer resolved. Moreover, we also show that functional TMR-cytochrome c undergoes a response of identical magnitude regardless of the proportion of nonfunctional protein in the sample. As expected for a technique with single-molecule sensitivity, we demonstrate that PCH can directly observe the most relevant conformation, unlike ensemble fluorometry.
View details for Web of Science ID 000233849000008
View details for PubMedID 16314563
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Reaction products with internal energy beyond the kinematic limit result from trajectories far from the minimum energy path: An example from H+HBr -> H-2+Br
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2005; 127 (47): 16368-16369
Abstract
The importance of reactive trajectories straying far from the minimum energy path is demonstrated for the bimolecular reaction H + HBr --> H2(v', j') + Br at 53 kcal/mol collision energy. Product quantum state distributions are measured and calculated using the quasi-classical trajectory technique, and the calculations indicate that highly internally excited H2 products result from indirect reactive trajectories with bent transition states. A general argument is made suggesting that reaction products with internal energy exceeding a kinematic constraint can, in general, be attributed to reactive collisions straying far from the minimum energy path.
View details for DOI 10.1021/ja055440a
View details for PubMedID 16305203
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Duty cycle and modulation efficiency of two-channel Hadamard transform time-of-flight mass spectrometry
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
2005; 16 (11): 1888-1901
Abstract
Hadamard transform time-of-flight mass spectrometry (HT-TOFMS) is based on the pseudorandom gating of ion packets into a time-of-flight mass-to-charge analyzer. In its typical implementation, the technique is able to monitor continuous ion sources with a 50% duty cycle, independent of all other figures of merit. Recently, we have demonstrated that the duty cycle can be extended to 100% using patterned, two-channel detection. Two-channel HT-TOFMS involves the simultaneous optimization of paired one-channel experiments and imposes more stringent conditions to achieve high-quality spectra. An ion modulation device, known as Bradbury-Nielson Gate (BNG), is central to HT-TOFMS. It is an ideal deflection plate, capable of transmitting or deflecting an ion beam according to a known binary sequence without changing the times-of-flight of the ions. Analytical equations are derived that accurately describe the ion modulation process of the BNG as confirmed by good agreement with SimIon simulations and ion beam imaging experiments. From these expressions, the duty cycle and ion modulation efficiency were calculated for various BNG parameters, ion beam characteristics, and detector dimensions, which permit the optimum conditions to be chosen for the two-channel experiment. We conclude that the outer detector should be three times the maximum deflection angle to detect all deflected ions (100% duty cycle) and that the difference between the modulated ion counts in the sequence elements 0 and 1 should be maximized to achieve high modulation efficiency. This condition is best achieved by tight focusing of the ion beam in the center of the inner detector. When both channels are optimized, the two-channel advantage can be exploited to achieve a further improvement over a single-channel experiment.
View details for DOI 10.1016/j.jasms.2005.07.025
View details for Web of Science ID 000233095600020
View details for PubMedID 16198595
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Undulatory delamination of thin polymer films on gold surfaces
JOURNAL OF PHYSICAL CHEMISTRY B
2005; 109 (41): 19416-19421
Abstract
Using two-dimensional surface plasmon resonance measurements, we have observed the formation of traveling waves in the delamination of thin films of polydimethylsilane (PDMS) exposed to methanol. Films were spin-coated on a gold surface and the methanol was added to the top surface. The stress-induced instability caused by the swelling of the PDMS thin film when its edge is pinned to the gold surface leads to wrinkle formation and propagation at the interface. The periodic pattern is thought to be the result of an Asaro-Tiller-Grinfeld (ATG) instability.
View details for DOI 10.1021/jp0535644
View details for Web of Science ID 000232612100056
View details for PubMedID 16853508
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Effects of C-H stretch excitation on the H+CH4 reaction
JOURNAL OF CHEMICAL PHYSICS
2005; 123 (13)
Abstract
We have investigated the effects of C-H stretching excitation on the H+CH4-->CH3+H2 reaction dynamics using the photo-LOC technique. The CH3 product vibrational state and angular distribution are measured for the reaction of fast H atoms with methane excited in either the antisymmetric stretching fundamental (nu3=1) or first overtone (nu3=2) with a center-of-mass collision energy of Ecoll ranging from 1.52 to 2.20 eV. We find that vibrational excitation of the nu3=1 mode enhances the overall reaction cross section by a factor of 3.0+/-1.5 for Ecoll=1.52 eV, and this enhancement factor is approximately constant over the 1.52-2.20-eV collision energy range. A local-mode description of the CH4 stretching vibration, in which the C-H oscillators are uncoupled, is used to describe the observed state distributions. In this model, the interaction of the incident H atom with either a stretched or an unstretched C-H oscillator determines the vibrational state of the CH3 product. We also compare these results to the similar quantities obtained previously for the Cl+CH4-->CH3+HCl reaction at Ecoll=0.16 eV [Z. H. Kim, H. A. Bechtel, and R. N. Zare, J. Chem. Phys. 117, 3232 (2002); H. A. Bechtel, J. P. Camden, D. J. A. Brown, and R. N. Zare, ibid. 120, 5096 (2004)] in an attempt to elucidate the differences in reactivity for the same initially prepared vibration.
View details for DOI 10.1063/1.2034507
View details for Web of Science ID 000232442500016
View details for PubMedID 16223282
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Phenanthrene and pyrene sorption and intraparticle diffusion in polyoxymethylene, coke, and activated carbon
ENVIRONMENTAL SCIENCE & TECHNOLOGY
2005; 39 (17): 6516-6526
Abstract
We report sorption isotherms and uptake kinetics for phenanthrene and pyrene with three organic model sorbents: polyoxymethylene (POM), coke, and activated carbon. We combine batch equilibration and kinetic experiments with the direct observation of the long-term diffusion of phenanthrene and pyrene as measured within cross-sectioned particles using microprobe laser-desorption laser-ionization mass spectroscopy (muL2MS). For POM pellets, the intraparticle concentration profiles predicted from kinetic batch experiments and a polymer diffusion model with spherical geometry are in agreement with the independent muL2MS measurements. For coke particles, the apparent diffusivities decreased with smaller particle size. These trends in diffusivities were described by a sorption-retarded pore diffusion model with a particle-size-dependent solid-water partitioning coefficient obtained from apparent equilibrium observed in the kinetic batch studies. For activated carbon, the muL2MS measurements showed faster radial diffusion of phenanthrene and pyrene into the particle interior than predicted from diffusion models based on a single sorption domain and diffusivity. A branched pore kinetic model, comprising polycyclic aromatic hydrocarbon (PAH) macropore diffusion with kinetic exchange of PAH between macroporous and microporous domains, fits the experimental observations better. Because of parallel macro- and microdiffusion processes, nonlinear sorption isotherms, and a concentration-dependent diffusivity, it is not possible to make independent parameter estimations for intraparticle diffusion in activated carbon using our present procedures.
View details for DOI 10.1021/es050113o
View details for Web of Science ID 000231723800035
View details for PubMedID 16190207
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A reinterpretation of the mechanism of the simplest reaction at an sp3-hybridized carbon atom: H + CD4 --> CD3 + HD.
Journal of the American Chemical Society
2005; 127 (34): 11898-11899
Abstract
A comparison between theory and experiment for the benchmark H + CD4 --> HD + CD3 abstraction reaction yields a reinterpretation of the reaction mechanism and highlights the unexpected contribution of a stripping mechanism. Whereas the best analytic surface fails to reproduce experiment, a first-principles direct-dynamics (on the fly) treatment is in good agreement, showing that the H + CD4 reaction exhibits extreme sensitivity to modest differences in the potential energy surface. We find that bent H-D-C transition state geometries play an important role in the dynamics. A simple model that relates the scattering angle impact parameter and cone of acceptance accounts well for the overall reaction dynamics.
View details for PubMedID 16117502
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A reinterpretation of the mechanism of the simplest reaction at an spa-hybridized carbon atom: H+CD4 -> CD3+HD
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2005; 127 (34): 11898-11899
Abstract
A comparison between theory and experiment for the benchmark H + CD4 --> HD + CD3 abstraction reaction yields a reinterpretation of the reaction mechanism and highlights the unexpected contribution of a stripping mechanism. Whereas the best analytic surface fails to reproduce experiment, a first-principles direct-dynamics (on the fly) treatment is in good agreement, showing that the H + CD4 reaction exhibits extreme sensitivity to modest differences in the potential energy surface. We find that bent H-D-C transition state geometries play an important role in the dynamics. A simple model that relates the scattering angle impact parameter and cone of acceptance accounts well for the overall reaction dynamics.
View details for DOI 10.1021/ja052684m
View details for Web of Science ID 000231605900010
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Collision-energy dependence of HD(nu(')=1,j ') product rotational distributions for the H+D-2 reaction
JOURNAL OF CHEMICAL PHYSICS
2005; 123 (5)
Abstract
Product rotational distributions for the reaction H + D2 --> HD(nu'=1,j') + D have been measured for 16 collision energies in the range of 1.43 < or = E(coll) < or = 2.55 eV. Time-dependent quantum-mechanical calculations agree well in general with the experimental results, but they consistently yield slightly colder distributions. In terms of the average energy channeled into rotation, the differences between experiment and theory amount to approximately 10% for all collision energies sampled. No peculiarity is found for E(coll)=2.55 eV at which the system has sufficient energy to access the first HD2 electronically excited state.
View details for DOI 10.1063/1.1978871
View details for Web of Science ID 000231168700022
View details for PubMedID 16108638
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Enhanced proteolytic activity of covalently bound enzymes in photopolymerized sol gel.
Analytical chemistry
2005; 77 (14): 4604-4610
Abstract
Trypsin is covalently linked to a photopolymerized sol-gel monolith modified by incorporating poly(ethylene glycol) (PSG-PEG) for on-column digestion of N(alpha)-benzoyl-l-arginine ethyl ester (BAEE) and two peptides, neurotensin and insulin chain B. The coupling of the enzyme to the monolith is via room-temperature Schiff chemistry in which an alkoxysilane reagent (linker) with an aldehyde functional group links to an inactive amine on trypsin to form an imine bond. The proteolytic activity of the immobilized trypsin was measured by monitoring the formation of N alpha-benzoyl-L-arginine (BA), the digestion product of BAEE. The BA is separated from BAEE by capillary electrophoresis and detected downstream (18.5 cm from the microreactor) by absorption (254 nm). Using the Bradford assay, we determined that 97 ng of trypsin is bound to the 1-cm microreactor located at the entrance of capillary column. The bioactivity of the trypsin-PSG-PEG microreactor at 20 degrees C for the digestion of BAEE was found to be 2270 units/mg of immobilized trypsin. The bioactivity of trypsin bound to the capillary wall in the open segment upstream from the monolith was 332 units/mg of immobilized trypsin under the same conditions. In contrast, the activity of free trypsin could not be observed for the digestion of BAEE at 20 degrees C after 16 h of incubation time.
View details for PubMedID 16013879
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Enhanced proteolytic activity enzymes in photopolymerized of covalently bound sol gel
ANALYTICAL CHEMISTRY
2005; 77 (14): 4604-4610
Abstract
Trypsin is covalently linked to a photopolymerized sol-gel monolith modified by incorporating poly(ethylene glycol) (PSG-PEG) for on-column digestion of N(alpha)-benzoyl-l-arginine ethyl ester (BAEE) and two peptides, neurotensin and insulin chain B. The coupling of the enzyme to the monolith is via room-temperature Schiff chemistry in which an alkoxysilane reagent (linker) with an aldehyde functional group links to an inactive amine on trypsin to form an imine bond. The proteolytic activity of the immobilized trypsin was measured by monitoring the formation of N alpha-benzoyl-L-arginine (BA), the digestion product of BAEE. The BA is separated from BAEE by capillary electrophoresis and detected downstream (18.5 cm from the microreactor) by absorption (254 nm). Using the Bradford assay, we determined that 97 ng of trypsin is bound to the 1-cm microreactor located at the entrance of capillary column. The bioactivity of the trypsin-PSG-PEG microreactor at 20 degrees C for the digestion of BAEE was found to be 2270 units/mg of immobilized trypsin. The bioactivity of trypsin bound to the capillary wall in the open segment upstream from the monolith was 332 units/mg of immobilized trypsin under the same conditions. In contrast, the activity of free trypsin could not be observed for the digestion of BAEE at 20 degrees C after 16 h of incubation time.
View details for DOI 10.1021/ac0504767
View details for Web of Science ID 000230530300042
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Correlated energy disposal and scattering dynamics of the Cl+CD4( v(3)=2) reaction
MOLECULAR PHYSICS
2005; 103 (13): 1837-1846
View details for DOI 10.1080/00268970500044814
View details for Web of Science ID 000229940900016
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Peak height precision in Hadamard transform time-of-flight mass spectra
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
2005; 16 (7): 1117-1130
View details for DOI 10.1016/j.jasms.2005.02.022
View details for Web of Science ID 000230045500016
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Extracts of impact breccia samples from Sudbury, Gardnos, and Ries impact craters and the effects of aggregation on C-60 detection
GEOCHIMICA ET COSMOCHIMICA ACTA
2005; 69 (11): 2891-2899
View details for DOI 10.1016/j.gca.2004.11.023
View details for Web of Science ID 000229759400014
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Strange Fizzical Attraction - 2004 James Flack Norris Award, sponsored by the Northeastern Section of the ACS
JOURNAL OF CHEMICAL EDUCATION
2005; 82 (5): 673-675
View details for Web of Science ID 000228300200002
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Effect of bin time on the photon counting histogram for one-photon excitation
CHEMPHYSCHEM
2005; 6 (5): 905-912
Abstract
We have demonstrated that our photon counting histogram (PCH) model with the correction for one-photon excitation is valid at multiple bin times. The fitted apparent brightness and concentration follow the three-dimensional diffusion model. More importantly, the semi-empirical parameter, F, introduced in the PCH model for one-photon excitation to correct for the non-Gaussian shape of the observation volume, shows small variations with different bin times. These variations are consistent with the physical interpretation of F, and they do not affect the resolving power of the PCH model for one-photon excitation. Based on these findings, we extend the time-independent PCH analysis to time-dependent photon counting multiple histograms (PCMH). This model considers the effect of bin time on the PCH parameters in a way that is similar to fluorescence intensity multiple distribution analysis (FIMDA). From the same set of data, PCMH extracts time-dependent parameters (diffusion time and triplet-state relaxation time) as well as time-independent parameters (true specific brightness and true average number of molecules). Given a three- to fourfold experimental difference in molecular brightness, we find that PCMH can resolve each species in a two-species sample and extract their respective diffusion times even when fluorescence correlation spectroscopy cannot.
View details for DOI 10.1002/cphc.200400547
View details for Web of Science ID 000229133300017
View details for PubMedID 15884075
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Evanescent-wave cavity ring-down investigation of polymer/solvent interactions
JOURNAL OF PHYSICAL CHEMISTRY B
2005; 109 (15): 7435-7442
Abstract
Evanescent-wave cavity ring-down spectroscopy (EW-CRDS) is used to measure interfacial phenomena when methanol or water is placed in contact with a film of poly(dimethylsiloxane) (PDMS), which is attached to the face of a fused-silica prism that constitutes part of a ring cavity. In the first few minutes after contact, the uptake of methanol is slower than that of water, but after this initial period the methanol diffuses more rapidly in the film than water does. Bulk weight-gain measurements confirm this result and yield diffusion coefficients of (25.1 +/- 0.7) x 10(-7) cm(2)/s for methanol in PDMS and (7 +/- 2) x 10(-7) cm(2)/s for water in PDMS. The interfacial optical losses found in the EW-CRDS measurements result primarily from scatter. In particular, we find that delamination of the film from the fused-silica substrate dominates the optical losses in the case of methanol. This conclusion is confirmed by separate surface plasmon resonance experiments.
View details for DOI 10.1021/jp050045s
View details for Web of Science ID 000228419100074
View details for PubMedID 16851852
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A soft on-column metal coating procedure for robust sheathless electrospray emitters used in capillary electrophoresis-mass spectrometry
ELECTROPHORESIS
2005; 26 (7-8): 1358-1365
Abstract
An on-column metal coating procedure was developed for sheathless electrospray emitters, based on Justus von Liebig's electroless silver mirror reaction followed by electrochemical deposition of gold onto the silver layer. The coating procedure is straightforward, mild, inexpensive, and can be performed with standard laboratory equipment. A long-term (600 h) stability investigation of the conductive coating was carried out by continuous electrospray in the positive electrospray mode, and no degradation in performance was found. The simplicity of the coating procedure and the robustness of the spray tips makes the spray tips highly suitable to couple delicate wall-coated or monolithic capillary columns to mass spectrometry. Peptide mixtures were separated by capillary electrophoresis and injected into either a Hadamard-transform time-of-flight mass analyzer or a commercial quadrupole mass analyzer using the described sheathless electrospray emitters. The performance was judged to be excellent.
View details for DOI 10.1002/elps.200410152
View details for Web of Science ID 000228784000009
View details for PubMedID 15759300
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Molecular orientation study of methylene blue at an air/fused-silica interface using evanescent-wave cavity ring-down spectroscopy
JOURNAL OF PHYSICAL CHEMISTRY B
2005; 109 (8): 3330-3333
Abstract
Using evanescent-wave cavity ring-down spectroscopy (EW-CRDS), we monitored the change in the absorbance of a thin film of methylene blue (MB) at an air/fused-silica interface while varying the polarization of the incident light (600 nm). We derived the average orientation angle of the planar MB molecules with respect to the surface normal and observed that the average orientation angle decreases as the surface concentration increases. At low surface concentrations, the MB molecules lie almost flat on the surface, whereas at higher surface concentrations the molecules become vertically oriented.
View details for DOI 10.1021/jp045290a
View details for Web of Science ID 000227247100037
View details for PubMedID 16851361
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Alkylation of polycyclic aromatic hydrocarbons in carbonaceous chondrites
GEOCHIMICA ET COSMOCHIMICA ACTA
2005; 69 (5): 1349-1357
View details for DOI 10.1016/j.gca.2004.09.009
View details for Web of Science ID 000227638900021
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Gold nanoparticles as a colorimetric sensor for protein conformational changes
CHEMISTRY & BIOLOGY
2005; 12 (3): 323-328
Abstract
Spherical gold nanoparticles and flat gold films are prepared in which yeast iso-1-cytochrome c (Cyt c) is covalently bound to the gold surface by a thiol group in the cystein 102 residue. Upon exposure to solutions of different pH, bound Cyt c unfolds at low pH and refolds at high pH. This conformational change causes measurable shifts in the color of the coated nanoparticle solutions detected by UV-VIS absorption spectroscopy and in the refractive index (RI) of the flat gold films detected by surface plasmon resonance (SPR) spectroscopy. Both experiments demonstrate the same trend with pH, suggesting the use of protein-covered gold nanoparticles as a simple colorimetric sensor for conformational change.
View details for DOI 10.1016/j.chembiol.2005.01.013
View details for Web of Science ID 000228260000011
View details for PubMedID 15797216
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Effect of bending and torsional mode excitation on the reaction Cl+CH4 -> HCl+CH3
JOURNAL OF CHEMICAL PHYSICS
2005; 122 (8)
Abstract
A beam containing CH(4), Cl(2), and He is expanded into a vacuum chamber where CH(4) is prepared via infrared excitation in a combination band consisting of one quantum of excitation each in the bending and torsional modes (nu(2)+nu(4)). The reaction is initiated by fast Cl atoms generated by photolysis of Cl(2) at 355 nm, and the resulting CH(3) and HCl products are detected in a state-specific manner using resonance-enhanced multiphoton ionization (REMPI). By comparing the relative amplitudes of the action spectra of Cl+CH(4)(nu(2)+nu(4)) and Cl+CH(4)(nu(3)) reactions, we determine that the nu(2)+nu(4) mode-driven reaction is at least 15% as reactive as the nu(3) (antisymmetric stretch) mode-driven reaction. The REMPI spectrum of the CH(3) products shows no propensity toward the formation of umbrella bend mode excited methyl radical, CH(3)(nu(2)=1), which is in sharp distinction to the theoretical expectation based on adiabatic correlations between CH(4) and CH(3). The rotational distribution of HCl(v=1) products from the Cl+CH(4)(nu(2)+nu(4)) reaction is hotter than the corresponding distribution from the Cl+CH(4)(nu(3)) reaction, even though the total energies of the two reactions are the same within 4%. An explanation for this enhanced rotational excitation of the HCl product from the Cl+CH(4)(nu(2)+nu(4)) reaction is offered in terms of the projection of the bending motion of the CH(4) reagent onto the rotational motion of the HCl product. The angular distributions of the HCl(nu=0) products from the Cl+CH(4)(nu(2)+nu(4)) reaction are backward scattered, which is in qualitative agreement with theoretical calculation. Overall, nonadiabatic product vibrational correlation and mode specificity of the reaction indicate that either the bending mode or the torsional mode or both modes are strongly coupled to the reaction coordinate.
View details for DOI 10.1063/1.1844295
View details for Web of Science ID 000227372200025
View details for PubMedID 15836035
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Moving beyond traditional UV-visible absorption detection: Cavity ring-down spectroscopy for HPLC
ANALYTICAL CHEMISTRY
2005; 77 (4): 1177-1182
Abstract
We describe the use of liquid-phase continuous-wave cavity ring-down spectroscopy for the detection of an HPLC separation. This technique builds on earlier work by Snyder and Zare using pulsed laser sources and improves upon commercially available UV-visible detectors by a factor of up to 50. The system employs a compact doubled-diode single-mode continuous-wave laser operating at 488 nm and a previously described Brewster's-angle flow cell. Ring-down time constants as long as 5.8 micros were observed with liquid samples in a 0.3-mm path length cell. The baseline noise during an HPLC separation was only 2 x 10(-7) absorbance units (AU) peak to peak, as compared to 1 x 10(-5) AU for a state-of-the-art commercial UV-visible detector.
View details for DOI 10.1021/ac048444r
View details for Web of Science ID 000227111200031
View details for PubMedID 15859003
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Inductive behavior of electrolytes in AC conductance measurements
CHEMICAL PHYSICS LETTERS
2005; 402 (1-3): 274-278
View details for DOI 10.1016/j.cplett.2004.12.047
View details for Web of Science ID 000226479900052
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Coating of poly(dimethylsiloxane) with n-dodecyl-beta-D-maltoside to minimize nonspecific protein adsorption
LAB ON A CHIP
2005; 5 (10): 1005-1007
Abstract
Poly(dimethylsiloxane)(PDMS) surface is coated with n-dodecyl-beta-D-maltoside, which reduces the nonspecifically adsorbed protein on the PDMS surface to the single molecule level.
View details for DOI 10.1039/b509251e
View details for Web of Science ID 000232003200001
View details for PubMedID 16175253
- Plasma Diagnostics Non-Equilibrium Air Plasmas at Atmospheric Pressure edited by Becker, K. H., Kogelschatz, U., Schoenbach, K. H., Barker, R. J. Institute of Physics Publishing: Bristol. 2005: 446–536
- Bursting Bubbles The Nucleus 2005; 83: 9-10
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Construction of microfluidic chips using polydimethylsiloxane for adhesive bonding
LAB ON A CHIP
2005; 5 (12): 1393-1398
Abstract
A thin layer of polydimethylsiloxane (PDMS) prepolymer, which is coated on a glass slide, is transferred onto the embossed area surfaces of a patterned substrate. This coated substrate is brought into contact with a flat plate, and the two structures are permanently bonded to form a sealed fluidic system by thermocuring (60 degrees C for 30 min) the prepolymer. The PDMS exists only at the contact area of the two surfaces with a negligible portion exposed to the microfluidic channel. This method is demonstrated by bonding microfluidic channels of two representative soft materials (PDMS substrate on a PDMS plate), and two representative hard materials (glass substrate on a glass plate). The effects of the adhesive layer on the electroosmotic flow (EOF) in glass channels are calculated and compared with the experimental results of a CE separation. For a channel with a size of approximately 10 to 500 microm, a approximately 200-500 nm thick adhesive layer creates a bond without voids or excess material and has little effect on the EOF rate. The major advantages of this bonding method are its generality and its ease of use.
View details for DOI 10.1039/b510494g
View details for Web of Science ID 000233276100009
View details for PubMedID 16286971
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Effects of bending excitation on the reaction of chlorine atoms with methane
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2005; 44 (16): 2382-2385
View details for DOI 10.1002/anie.200462837
View details for Web of Science ID 000228709200016
View details for PubMedID 15765488
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Capillary electrophoretic and micellar electrokinetic separations of asymmetric dimethyl-L-arginine and structurally related amino acids: Quantitation in human plasma
JOURNAL OF SEPARATION SCIENCE
2004; 27 (17-18): 1483-1490
Abstract
We report the development of efficient electrophoretic methods for the separation and quantification of L-arginine and six naturally occurring derivatives that are structurally and functionally related. Capillary electrophoresis (CE) employing a concentrated borate buffer at pH 9.4 achieves the separation of mixtures containing dimethyl-L-arginine, NG-monomethyl-L-arginine, L-arginine, L-homoarginine, L-ornithine, and L-citrulline as 4-fluoro-7-nitrobenzofurazan derivatives. In addition, the separation of the isomeric dimethyl-L-arginine derivatives (symmetric and asymmetric) is attained with baseline resolution by micellar electrokinetic chromatography (MEKC) when a high concentration of deoxycholic acid is added as a surfactant to the same running buffer. The influence of buffer type, concentration, and pH on the separation was studied to optimize separation conditions. The limit of quantitation (LOQ) for asymmetric dimethyl-L-arginine in aqueous solution was determined to be 20 microM using UV absorption in a CE separation and 0.1 microM using laser induced fluorescence (LIF) detection in an MEKC separation. This newly developed method was successfully applied for the quantitation of asymmetric dimethyl-L-arginine and L-arginine in human plasma samples at levels that might be used as a clinical diagnostic for cardiovascular disease (0.125 microM LOQ).
View details for DOI 10.1002/jssc.200401918
View details for Web of Science ID 000225938100011
View details for PubMedID 15638156
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Optical-optical double resonance photoionization spectroscopy of nf Rydberg states of nitric oxide
JOURNAL OF CHEMICAL PHYSICS
2004; 121 (20): 9938-9947
Abstract
The spectra of vibrationally excited nf Rydberg states of nitric oxide were recorded by monitoring the photoion current produced using two-photon double resonance excitation via the NO A (2)Sigma(+) state followed by photoexcitation of the Rydberg state that undergoes autoionization. The optical transition intensities from NO A state to nf Rydberg states were calculated, and the results agree closely with experiment. These results combined with circular dichroism measurements allow us to assign rotational quantum numbers to the nf Rydberg states even in a spectrum of relatively low resolution. We report the positions of these nf (upsilon,N,N(c)) Rydberg levels converging to the NO X (1)Sigma(+) upsilon(+) = 1 and 2 ionization limits where N is the total angular momentum excluding electron and nuclear spin and N(c) represents the rotational quantum number of the ion core. Our two-color optical-optical double resonance measurements cover the range of N from 15 to 28, N(c) from 14 to 29, and the principal quantum number n from 9 to 21. The electrostatic interaction between the Rydberg electron and the ion core is used to account for the rotational fine structure and a corresponding model is used to fit the energy levels to obtain the quadrupole moment and polarizability of the NO(+) core. Comparison with a multichannel quantum defect theory fit to the same data confirms that the model we use for the electrostatic interaction between the nf Rydberg electron and the ion core of NO well describes the rotational fine structure.
View details for DOI 10.1063/1.1807373
View details for Web of Science ID 000225042700020
View details for PubMedID 15549868
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Photon counting histogram: One-photon excitation
CHEMPHYSCHEM
2004; 5 (10): 1523-1531
Abstract
The photon counting histogram (PCH) analysis is a fluorescence fluctuation method that is able to characterize the brightness and concentration of different fluorescent species present in a liquid sample. We find that the PCH model using a three-dimensional Gaussian observation volume profile is inadequate for fitting experimental data obtained from a confocal setup with one-photon excitation. We propose an imoroved model, which is based on the correction to the observation volume profile for the out-of-focus emission. We demonstrate that this model is able to resolve different species present under a wide range of conditions. Attention is given to how this model allows the examination of the effects of different instrumental setups on the resolvability.
View details for DOI 10.1002/cphc.200400176
View details for Web of Science ID 000224692100008
View details for PubMedID 15535551
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Rovibrational product state distribution for inelastic H+D-2 collisions
JOURNAL OF CHEMICAL PHYSICS
2004; 121 (14): 6587-6590
Abstract
Experimental measurements of rovibrational product state distributions for the inelastic scattering process H + D2(nu=0,j)-->H + D2(nu' = 1,2,j') are presented and compared with the results of quasiclassical and quantum mechanical calculations. Agreement between theory and experiment is almost quantitative. Two subtle trends are found: the relative amount of energy in product rotational excitation decreases slightly with increasing collision energy and increases slightly with increasing product vibrational excitation. These trends are the reverse of what has been found for reactive scattering in which the opposite trends are much more pronounced.
View details for DOI 10.1063/1.1804940
View details for Web of Science ID 000224269200001
View details for PubMedID 15473712
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Probing excited electronic states using vibrationally mediated photolysis: Application to hydrogen iodide
JOURNAL OF PHYSICAL CHEMISTRY A
2004; 108 (39): 7806-7813
View details for DOI 10.1021/jp49051z
View details for Web of Science ID 000224071600006
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Application of ion chromatography to the investigation of real-world samples
JOURNAL OF CHEMICAL EDUCATION
2004; 81 (9): 1299-1302
View details for Web of Science ID 000223203100015
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Chemical cytometry on a picoliter-scale integrated microfluidic chip
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2004; 101 (35): 12809-12813
Abstract
An integrated microfluidic device has been fabricated for analyzing the chemical contents of a single cell (chemical cytometry). The device is designed to accomplish four different functions: (i) cell handling, (ii) metering and delivering of chemical reagents, (iii) cell lysis and chemical derivatization, and (iv) separating derivatized compounds and detecting them by laser-induced fluorescence. These functions are accomplished with only two valves, formed by multilayer soft lithography. A new kind of three-state valve and a picopipette are described; these elements are crucial for minimizing the reaction volume and ensuring optimal shape of the channel for electrophoresis injection. By using these valves, a reaction volume of approximately 70 pl is achieved for the lysis and derivitization of the contents of a single Jurkat T cell (approximately 10 microm diameter). As a demonstration of the use of this integrated microfluidic device, electropherograms of amino acids from individual Jurkat T cells are recorded and compared with those collected from a multiple-cell homogenate.
View details for DOI 10.1073/pnas.0405299101
View details for Web of Science ID 000223694700008
View details for PubMedID 15328405
View details for PubMedCentralID PMC516477
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Application of EW-CRDS to the study of solvent diffusion in polymers.
AMER CHEMICAL SOC. 2004: U155
View details for Web of Science ID 000223712800611
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Walk-off ring-down spectroscopy: attaining ultrafast resolution by converting time into space
18th Colloquium on High Resolution Molecular Spectroscopy
TAYLOR & FRANCIS LTD. 2004: 1501–8
View details for DOI 10.1080/00268970410001725819
View details for Web of Science ID 000225105500002
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Line strength factors for E,F-1 Sigma(+)(g)(v '=0, J '=J '')-X-1 Sigma(+)(g) (v '', J '') (2+1) REMPI transitions in molecular hydrogen
CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE
2004; 82 (6): 723-729
View details for DOI 10.1139/V04-074
View details for Web of Science ID 000224450700007
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Surface plasmon resonance analysis of aqueous mercuric ions
SENSORS AND ACTUATORS B-CHEMICAL
2004; 99 (2-3): 216-222
View details for DOI 10.1016/j.snb.2003.11.015
View details for Web of Science ID 000221580100003
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Factors affecting quantitative analysis in laser desorption/laser ionization mass spectrometry
ANALYTICAL CHEMISTRY
2004; 76 (9): 2430-2437
Abstract
Microprobe laser desorption/laser ionization mass spectrometry (microL(2)MS) is a sensitive and selective technique that has proven useful in the qualitative and semiquantitative detection of trace organic compounds, particularly polycyclic aromatic hydrocarbons (PAHs). Recent efforts have focused on developing microL(2)MS as a quantitative method, often by measuring the ratio of signal strength of an analyte to an internal standard. Here, we present evidence of factors that affect these ratios and thus create uncertainty and irreproducibility in quantification. The power and wavelength of the desorption laser, the delay time between the desorption and ionization steps, the power of the ionization laser, and the ionization laser alignment are all shown to change PAH ratios, in some cases by up to a factor of 24. Although changes in the desorption laser parameters and the delay time cause the largest effects, the ionization laser power and alignment are the most difficult parameters to control and thus provide the most practical limitations for quantitative microL(2)MS. Variation in ratios is seen in both synthetic poly(vinyl chloride) membranes and in "real-life" samples of Murchison meteorite powder. Ratios between similar PAHs vary less than those between PAHs that differ greatly in mass and structure. This finding indicates that multiple internal standards may be needed for quantification of samples containing diverse PAHs.
View details for DOI 10.1021/ac0354140
View details for Web of Science ID 000221205900010
View details for PubMedID 15117180
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Electroosmotic flow in a poly(dimethylsiloxane) channel does not depend on percent curing agent
ELECTROPHORESIS
2004; 25 (7-8): 1120-1124
Abstract
Poly(dimethylsiloxane) (PDMS) microfluidic devices were prepared from different ratios of "curing agent" (which contains silicon hydride groups) to "base" (which contains vinyl-terminated noncross-linked PDMS), to determine the effect of this ratio on electroosmotic flow (EOF). In fabricating devices for this purpose, a novel method for permanently enclosing PDMS channels was developed. As a supplement to the microfluidic method, the inner walls of capillaries were coated with PDMS formed from varying ratios of curing agent to base. EOF was found to be constant for PDMS formed with each ratio, which implies that the negative surface charges do not arise from chemical species present only in the base or the curing agent.
View details for DOI 10.1002/elps.200305784
View details for Web of Science ID 000221168700024
View details for PubMedID 15095455
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Integration of on-line protein digestion, peptide separation, and protein identification using pepsin-coated photopolymerized sol-gel columns and capillary electrophoresis/mass spectrometry
ANALYTICAL CHEMISTRY
2004; 76 (7): 1896-1902
Abstract
A miniaturized pepsin reactor was prepared inside a fused-silica capillary (i.d. 75 microm) by coating a pepsin-containing gel on a photopolymerized porous silica monolith. The pepsin-encapsulated film was prepared by a sol-gel method. The sol-gel reaction was optimized so that the sol solution containing pepsin forms a thin film on the photopolymerized sol-gel (PSG) monolith that was initially fabricated at the inlet of the capillary. Pepsin was encapsulated into the gel matrix without losing its activity. The large surface area of the PSG monolith enabled the immobilized pepsin to achieve a high catalytic turnover rate, and the porous nature of the PSG promotes penetration of large molecular proteins into the column. The immobilized pepsin-digested peptides and proteins, and the resulting mixture of peptide fragments, could be directly separated in the portion of the capillary where no PSG monolith exists. The durability and repeatability of the fabricated pepsin-coated column was tested and found to be satisfactory. An acidic solution consisting of 0.5 M formic acid was used as the running buffer, because it suppresses the adsorption of proteins or peptides on the inner surface of the capillary as well as enables direct connection of the output of the capillary electrophoresis column to a mass spectrometer. The on-line digestion of insulin chain beta and lysozyme provides identification of the proteolytic peptides. Recovery was achieved for 100% of the insulin chain beta amino acid sequence and 73% of the lysozyme amino acid sequence.
View details for DOI 10.1021/ac035107u
View details for Web of Science ID 000220618400022
View details for PubMedID 15053649
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Denaturation and renaturation of self-assembled yeast iso-1-cytochrome c on Au
ANALYTICAL CHEMISTRY
2004; 76 (7): 2112-2117
Abstract
We have made surface plasmon resonance (SPR) measurements of yeast iso-1-cytochrome c (Cyt c) on a gold surface. Angle-resolved SPR curves are recorded as a function of urea concentration before and after self-assembly of the Cyt c. Exposure to a urea solution causes denaturation of Cyt c, which shifts the minimum in the SPR curve to a larger angle and decreases the signal amplitude. The Gibbs free energy change for denaturation of the protein on Au is calculated from the change of the SPR signal amplitude with urea concentration. We find that (1) Cyt c can be reversibly denatured and renatured, depending on the urea concentration, and (2) the Gibbs free energy change for denaturation of Cyt c on Au surface in water, DeltaG degrees (water), is 1.5 kcal/mol, which is approximately 4 times less than that in bulk solution.
View details for DOI 10.1021/ac035416k
View details for Web of Science ID 000220618400050
View details for PubMedID 15053677
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Laboratory experiments of Titan tholin formed in cold plasma at various pressures: implications for nitrogen-containing polycyclic aromatic compounds in Titan haze
ICARUS
2004; 168 (2): 344-366
View details for DOI 10.1016/j.icarus.2003.12.014
View details for Web of Science ID 000220474300011
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Poly(dimethylsiloxane) microfluidic flow cells for surface plasmon resonance spectroscopy
SENSORS AND ACTUATORS B-CHEMICAL
2004; 98 (2-3): 208-214
View details for DOI 10.1016/j.snb.2003.06.004
View details for Web of Science ID 000220214300014
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Comparing the dynamical effects of symmetric and antisymmetric stretch excitation of methane in the Cl+CH4 reaction
JOURNAL OF CHEMICAL PHYSICS
2004; 120 (11): 5096-5103
Abstract
The effects of two nearly isoenergetic C-H stretching motions on the gas-phase reaction of atomic chlorine with methane are examined. First, a 1:4:9 mixture of Cl(2), CH(4), and He is coexpanded into a vacuum chamber. Then, either the antisymmetric stretch (nu(3)=3019 cm(-1)) of CH(4) is prepared by direct infrared absorption or the infrared-inactive symmetric stretch (nu(1)=2917 cm(-1)) of CH(4) is prepared by stimulated Raman pumping. Photolysis of Cl(2) at 355 nm generates fast Cl atoms that initiate the reaction with a collision energy of 1290+/-175 cm(-1) (0.16+/-0.02 eV). Finally, the nascent HCl or CH(3) products are detected state-specifically via resonance enhanced multiphoton ionization and separated by mass in a time-of-flight spectrometer. We find that the rovibrational distributions and state-selected differential cross sections of the HCl and CH(3) products from the two vibrationally excited reactions are nearly indistinguishable. Although Yoon et al. [J. Chem. Phys. 119, 9568 (2003)] report that the reactivities of these two different types of vibrational excitation are quite different, the present results indicate that the reactions of symmetric-stretch excited or antisymmetric-stretch excited methane with atomic chlorine follow closely related product pathways. Approximately 37% of the reaction products are formed in HCl(v=1,J) states with little rotational excitation. At low J states these products are sharply forward scattered, but become almost equally forward and backward scattered at higher J states. The remaining reaction products are formed in HCl(v=0,J) and have more rotational excitation. The HCl(v=0,J) products are predominantly back and side scattered. Measurements of the CH(3) products indicate production of a non-negligible amount of umbrella bend excited methyl radicals primarily in coincidence with the HCl(v=0,J) products. The data are consistent with a model in which the impact parameter governs the scattering dynamics.
View details for DOI 10.1063/1.1647533
View details for Web of Science ID 000220225000014
View details for PubMedID 15267378
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State-to-state dynamics of the Cl+CH3OH -> HCl+CH2OH reaction
JOURNAL OF CHEMICAL PHYSICS
2004; 120 (9): 4231-4239
Abstract
Molecular chlorine, methanol, and helium are co-expanded into a vacuum chamber using a custom designed "late-mixing" nozzle. The title reaction is initiated by photolysis of Cl2 at 355 nm, which generates monoenergetic Cl atoms that react with CH3OH at a collision energy of 1960 +/- 170 cm(-1) (0.24 +/- 0.02 eV). Rovibrational state distributions of the nascent HCl products are obtained via 2 + 1 resonance enhanced multiphoton ionization, center-of-mass scattering distributions are measured by the core-extraction technique, and the average internal energy of the CH3OH co-products is deduced by measuring the spatial anisotropy of the HCl products. The majority (84 +/- 7%) of the HCl reaction products are formed in HCl(v = 0) with an average rotational energy of [Erot] = 390 +/- 70 cm(-1). The remaining 16 +/- 7% are formed in HCl(v = 1) and have an average rotational energy of [Erot] = 190 +/- 30 cm(-1). The HCl(v = 1) products are primarily forward scattered, and they are formed in coincidence with CH2OH products that have little internal energy. In contrast, the HCl(v = 0) products are formed in coincidence with CH2OH products that have significant internal energy. These results indicate that two or more different mechanisms are responsible for the dynamics in the Cl + CH3OH reaction. We suggest that (1) the HCl(v = 1) products are formed primarily from collisions at high impact parameter via a stripping mechanism in which the CH2OH co-products act as spectators, and (2) the HCl(v = 0) products are formed from collisions over a wide range of impact parameters, resulting in both a stripping mechanism and a rebound mechanism in which the CH2OH co-products are active participants. In all cases, the reaction of fast Cl atoms with CH3OH is with the hydrogen atoms on the methyl group, not the hydrogen on the hydroxyl group.
View details for DOI 10.1063/1.1644797
View details for Web of Science ID 000189209200020
View details for PubMedID 15268590
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Collision energy dependence of the HD(nu(')=2) product rotational distribution of the H+D-2 reaction in the range 1.30-1.89 eV
JOURNAL OF CHEMICAL PHYSICS
2004; 120 (7): 3255-3264
Abstract
An experimental and theoretical investigation of the collision energy dependence of the HD(nu' = 2,j') rotational product state distribution for the H + D2 reaction in the collision energy range of Ecol = 1.30-1.89 eV has been carried out. Theoretical results based on time-dependent and time-independent quantum mechanical methods agree nearly perfectly with each other, and the agreement with the experiment is good at low collision energies and very good at high collision energies. This behavior is in marked contrast to a previous report on the HD(nu' = 3,j') product state rotational distribution [Pomerantz et al., J. Chem. Phys. 120, 3244 (2004)] where a systematic difference between experiment and theory was observed, especially at the highest collision energies. The reason for this different behavior is not yet understood. In addition, this study employs Doppler-free spectroscopy to resolve an ambiguity in the E, F-X resonantly enhanced multiphoton ionization transition originating from the HD(nu' = 2,j' = 1) state, which is found to be caused by an accidental blending with the transition coming from the HD(nu' = 1,j' = 14) state.
View details for DOI 10.1063/1.1641009
View details for Web of Science ID 000188880900025
View details for PubMedID 15268479
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Disagreement between theory and experiment in the simplest chemical reaction: Collision energy dependent rotational distributions for H+D-2 -> HD(nu(')=3,j('))+D
JOURNAL OF CHEMICAL PHYSICS
2004; 120 (7): 3244-3254
Abstract
We present experimental rotational distributions for the reaction H + D2 --> HD(nu' = 3,j') + D at eight different collision energies between 1.49 and 1.85 eV. We combine a previous measurement of the state-resolved excitation function for this reaction [Ayers et al., J. Chem. Phys. 119, 4662 (2003)] with the current data to produce a map of the relative reactive cross section as a function of both collision energy and rotational quantum number (an E-j' plot). To compare with the experimental data, we also present E-j' plots resulting from both time-dependent and time-independent quantum mechanical calculations carried out on the BKMP2 surface. The two calculations agree well with each other, but they produce rotational distributions significantly colder than the experiment, with the difference being more pronounced at higher collision energies. Disagreement between theory and experiment might be regarded as surprising considering the simplicity of this system; potential causes of this discrepancy are discussed.
View details for DOI 10.1063/1.1641008
View details for Web of Science ID 000188880900024
View details for PubMedID 15268478
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Design and characterization of a late-mixing pulsed nozzle
REVIEW OF SCIENTIFIC INSTRUMENTS
2004; 75 (2): 556-558
View details for DOI 10.1063/1.1641158
View details for Web of Science ID 000188532400043
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Bond and mode selectivity in the reaction of atomic chlorine with vibrationally excited CH2D2
JOURNAL OF CHEMICAL PHYSICS
2004; 120 (2): 791-799
Abstract
The title reaction is investigated by co-expanding a mixture of Cl2 and CH2D2 into a vacuum chamber and initiating the reaction by photolyzing Cl2 with linearly polarized 355 nm light. Excitation of the first C-H overtone of CH2D2 leads to a preference for hydrogen abstraction over deuterium abstraction by at least a factor of 20, whereas excitation of the first C-D overtone of CH2D2 reverses this preference by at least a factor of 10. Reactions with CH2D2 prepared in a local mode containing two quanta in one C-H oscillator /2000>- or in a local mode containing one quantum each in two C-H oscillators /1100> lead to products with significantly different rotational, vibrational, and angular distributions, although the vibrational energy for each mode is nearly identical. The Cl+CH2D2/2000>- reaction yields methyl radical products primarily in their ground state, whereas the Cl+CH2D2/1100> reaction yields methyl radical products that are C-H stretch excited. The HCl(v=1) rotational distribution from the Cl+CH2D2/2000>- reaction is significantly hotter than the HCl(v=1) rotational distribution from the Cl+CH2D2/1100> reaction, and the HCl(v=1) differential cross-section (DCS) of the Cl+CH2D2/2000>- reaction is more broadly side scattered than the HCl(v=1) DCS of the Cl+CH2D2/1100> reaction. The results can be explained by a simple spectator model and by noting that the /2000>- mode leads to a wider cone of acceptance for the reaction than the /1100> mode. These measurements represent the first example of mode selectivity observed in a differential cross section, and they demonstrate that vibrational excitation can be used to direct the reaction pathway of the Cl+CH2D2 reaction.
View details for DOI 10.1063/1.1630961
View details for Web of Science ID 000187718200031
View details for PubMedID 15267915
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Continuous two-channel time-of-flight mass spectrometric detection of electrosprayed ions
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2004; 43 (47): 6541-6544
View details for DOI 10.1002/anie.200461240
View details for Web of Science ID 000225718700026
View details for PubMedID 15578763
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Single molecule fluorescence studies of immobilized beta-2 adrenergic receptor
BIOPHYSICAL SOCIETY. 2004: 603A
View details for Web of Science ID 000187971203115
- Fizzical Attraction Nature 2004; 432: 954
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An evolutionary connection between interstellar ices and IDPs? Clues from mass spectroscopy measurements of laboratory simulations
2nd World Space Congress/34th COSPAR Scientific Assembly
PERGAMON-ELSEVIER SCIENCE LTD. 2004: 67–71
View details for DOI 10.1016/j.asr.2003.08.004
View details for Web of Science ID 000189505400009
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Photon counting histogram for one-photon excitation (vol 4, pg 1121, 2003)
CHEMPHYSCHEM
2003; 4 (12): 1280-1280
View details for Web of Science ID 000187663800001
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Single-cell immunosensors for protein detection
BIOSENSORS & BIOELECTRONICS
2003; 19 (4): 331-336
Abstract
A single-cell detector is described that combines the natural signal amplification of whole-cell biosensors with the flexibility and specificity of immunological recognition. An immune cell that expresses receptors for the constant region of immunoglobulin G (IgG) is loaded with a Ca(2+)-indicating dye and with antibodies directed against the protein of interest. Introduction of a multivalent protein antigen causes cross-linking of the receptors, which results in a detectable increase in the concentration of cytosolic Ca(2+). Some immune cell lines respond to stimulation with oscillations in their cytosolic Ca(2+) levels that complicate their use as detectors. The human monocytic cell line U-937, when treated with the cytokine interferon-gamma, produces a large, short-lived Ca(2+) signal in response to cross-linking of its high-affinity IgG receptors. U-937 was therefore chosen for development as an immunity-based detector. Human and rabbit antibodies are found to effectively stimulate the cell, causing a prompt and transient response. The cell is able to respond to repeated stimulation, though the response diminishes during rapid stimulation. Ovalbumin can be detected in micromolar concentrations. Possible fundamental constraints on the size of a detectable analyte are discussed.
View details for DOI 10.1016/S0956-5663(03)00190-8
View details for Web of Science ID 000186918900008
View details for PubMedID 14615091
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Photon counting histogram for one-photon excitation
CHEMPHYSCHEM
2003; 4 (10): 1121-1123
View details for DOI 10.1002/cphc.200300824
View details for Web of Science ID 000186151200016
View details for PubMedID 14596014
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Reflections on the development of Laboratory instrumentation
AMERICAN LABORATORY
2003; 35 (20): 24-?
View details for Web of Science ID 000186357100006
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Measurement of the cross section for H+D-2 -> HD(v(')=3,j '=0)+D as a function of angle and energy
JOURNAL OF CHEMICAL PHYSICS
2003; 119 (9): 4662-4670
View details for DOI 10.1063/1.1595092
View details for Web of Science ID 000184775200007
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PAH sorption mechanism and partitioning behavior in lampblack-impacted soils from former oil-gas plant sites
ENVIRONMENTAL SCIENCE & TECHNOLOGY
2003; 37 (16): 3625-3634
Abstract
This study assessed polycyclic aromatic hydrocarbon (PAH) association and aqueous partitioning in lampblack-impacted field soils from five sites in California that formerly housed oil-gas process operations. Lampblack is the solid residue resulting from the decomposition of crude oil at high temperatures in the gas-making operation and is coated or impregnated with oil gasification byproducts, among which PAHs are the compounds of the greatest regulatory concern. A suite of complementary measurements investigated the character of lampblack particles and PAH location and the associated effects on PAH partitioning between lampblack and water. PAH analyses on both whole samples and density-separated components demonstrated that 81-100% of PAHs in the lampblack-impacted soils was associated with lampblack particles. FTIR, 13C NMR, and SEM analyses showed that oil-gas lampblack solids comprise primarily aromatic carbon with soot-like structures. A free-phase aromatic oil may be present in some of the lampblack soils containing high PAH concentrations. Comparable long-term aqueous partitioning measurements were obtained with an air-bridge technique and with a centrifugation/alum flocculation procedure. Large solid/water partition coefficient (Kd) values were observed in samples exhibiting lower PAH and oil levels, whereas smaller Kd values were measured in lampblack samples containing high PAH levels. The former result is in agreement with an oil-soot partitioning model, and the latter is in agreement with a coal tar-water partitioning model. Lampblack containing high PAH levels appears to exhaust the sorption capacity of the soot-carbon, creating a free aromatic oil phase that exhibits partitioning behavior similar to PAHs in coal tar. This study improves mechanistic understanding of PAH sorption on aged lampblack residuals at former oil-gas sites and provides a framework for mechanistic assessment of PAH leaching potential and risk from such site materials.
View details for DOI 10.1021/es0262683
View details for Web of Science ID 000184803700022
View details for PubMedID 12953875
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Teaching effective communication in a writing-intensive analytical chemistry course
JOURNAL OF CHEMICAL EDUCATION
2003; 80 (8): 904-906
View details for Web of Science ID 000184143500010
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Adsorption of crystal violet to the silica-water interface monitored by evanescent wave cavity ring-down spectroscopy
JOURNAL OF PHYSICAL CHEMISTRY B
2003; 107 (29): 7070-7075
View details for DOI 10.1021/jp027636s
View details for Web of Science ID 000184242600022
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Microfluidic device for single-cell analysis
ANALYTICAL CHEMISTRY
2003; 75 (14): 3581-3586
Abstract
We have developed a novel microfluidic device constructed from poly(dimethylsiloxane) using multilayer soft lithography technology for the analysis of single cells. The microfluidic network enables the passive and gentle separation of a single cell from the bulk cell suspension, and integrated valves and pumps enable the precise delivery of nanoliter volumes of reagents to that cell. Various applications are demonstrated, including cell viability assays, ionophore-mediated intracellular Ca2+ flux measurements, and multistep receptor-mediated Ca2+ measurements. These assays, and others, are achieved with significant improvements in reagent consumption, analysis time, and temporal resolution over macroscale alternatives.
View details for DOI 10.1021/ac0340758
View details for Web of Science ID 000184649500041
View details for PubMedID 14570213
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Determination of glutamine and serine in rat cerebrospinal fluid using capillary electrochromatography with a modified photopolymerized sol-gel monolithic column
JOURNAL OF CHROMATOGRAPHY A
2003; 1004 (1-2): 209-215
Abstract
Capillary electrochromatographic separations of amino acid mixtures were studied using two modified porous photopolymerized sol-gel monolithic columns. One was modified with dimethyloctadecylchlorosilane (DMOS), and the other was modified with DMOS, followed by chlorotrimethylsilane to end-cap residual silanol groups. Prior to separation, amino acids were derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole using as a mobile phase 50 mM phosphate (pH 2.5), water, and acetonitrile in the ratio of 1:1:8. Five derivatized amino acids (Asn, Phe, Ala, Ile, and Leu) were separated within 7 min. Theoretical plate numbers varied between 58700 and 105000/m. This separation method with the end-capped monolithic column was applied to rat cerebrospinal fluid. The dominant amino acid found was Gln at a concentration of 420 microM along with small quantities of Ser (54 microM).
View details for DOI 10.1016/S0021-9673(03)00451-5
View details for Web of Science ID 000184296600023
View details for PubMedID 12929975
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Cavity ring-down spectroscopy as a detector for liquid chromatography
ANALYTICAL CHEMISTRY
2003; 75 (13): 3086-3091
Abstract
We have demonstrated the use of cavity ring-down spectroscopy (CRDS) as a detector for high performance liquid chromatography (HPLC). For this use, we have designed and implemented a Brewster's angle flow cell such that cavity ring-down spectroscopy can be performed on microliter volumes of liquids. The system exhibits a linear dynamic range of 3 orders of magnitude (30 nM to 30 microM quinalizarin at 470 nm) for static measurements and 2 orders of magnitude (0.5 microM to 50 microM) for HPLC measurements. For the static measurements, the baseline noise is 2.8 x 10(-6) AU rms and 1.0 x 10(-5) AU peak-to-peak, and for the HPLC separations, it is 3.2 x 10(-6) AU rms and 1.3 x 10(-5) AU peak-to-peak. The baseline noise is determined after the data are smoothed by an 11-point boxcar average. The peak areas detected from HPLC separations are reproducible to within 2-3%. The HPLC mass detection limit for a molecule with epsilon = 9 x 10(3) M(-1) cm(-1) in a 300-microm path length cell (illuminated volume, 0.5 microL) is reported as 2.5 x 10(-8) g/mL. These results were obtained using a simple pulsed CRDS system and are comparable to, if not better than, a high-quality commercial UV-vis absorption detector for the same path length.
View details for DOI 10.1021/ac0340152
View details for Web of Science ID 000183975300026
View details for PubMedID 12964755
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Photodissociation of O-2 via the Herzberg continuum: Measurements of O-atom alignment and orientation
JOURNAL OF CHEMICAL PHYSICS
2003; 118 (23): 10566-10574
View details for DOI 10.1063/1.1574511
View details for Web of Science ID 000183124300023
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Optical diagnostics of atmospheric pressure air plasmas
PLASMA SOURCES SCIENCE & TECHNOLOGY
2003; 12 (2): 125-138
View details for Web of Science ID 000183461900001
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Use of broadband, continuous-wave diode lasers in cavity ring-down spectroscopy for liquid samples
APPLIED SPECTROSCOPY
2003; 57 (5): 571-573
Abstract
Cavity ring-down spectroscopy (CRDS) is an extremely sensitive absorption technique that has been applied primarily to gas samples, which are characterized by having narrow absorption features. Recently, CRDS has also been applied to liquid samples, which have broad absorption features. The use of small inexpensive diode lasers as light sources for liquid samples is demonstrated. The low cost coupled with the ease and technical straightforwardness of application gives this technique wide appeal.
View details for Web of Science ID 000184358400016
View details for PubMedID 14658685
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Evidence that polycyclic aromatic hydrocarbons in two carbonaceous chondrites predate parent-body formation
GEOCHIMICA ET COSMOCHIMICA ACTA
2003; 67 (7): 1429-1436
View details for DOI 10.1016/S0016-7037(02)01277-2
View details for Web of Science ID 000181734000013
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Surface plasmon resonance detection for capillary electrophoresis separations
ANALYTICAL CHEMISTRY
2003; 75 (6): 1542-1547
Abstract
A miniaturized surface plasmon resonance sensor has been used as an on-line detector for capillary electrophoresis separations. The capillary was modified slightly to shield the sensor electronics from the high voltages applied during the separation. A three-component mixture of high refractive index materials was separated and detected at the millimolar level by an untreated gold-sensing surface. A simple protein immobilization procedure was used to functionalize the surface for selective protein detection. A hybrid buffer system was developed, in which both the deposition of immobilized protein layers and the electrophoretic delivery of protein analytes were optimized. The detection system has a reproducibility of 15%, a dynamic range of 3 orders of magnitude, and a detection limit for IgG of 2 fmol.
View details for DOI 10.1021/ac0263521
View details for Web of Science ID 000181675900042
View details for PubMedID 12659220
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Doppler-free multi-photon ionization: a proposal for enhancing ion images
CHEMICAL PHYSICS LETTERS
2003; 370 (3-4): 515-521
View details for DOI 10.1016/S0009-2614(03)00158-1
View details for Web of Science ID 000181386600034
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Effects of modulation defects on Hadamard transform time-of-flight mass spectrometry (HT-TOFMS)
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
2003; 14 (3): 278-286
Abstract
In any Hadamard multiplexing technique, discrepancies between the intended and the applied encoding sequences may reduce the intensity of real spectral features and create discrete, artificial signals. In our implementation of Hadamard transform time-of-flight mass spectrometry (HT-TOFMS), the encoding sequence is applied to the ion beam by means of an interleaved comb of wires (Bradbury-Nielson gate), which shutters the ion beam on and off. By isolating and exaggerating individual skewing effects in simulating the HT-TOFMS process, we determined the nature of errors that arise from various defects. In particular, we find that the most damaging defects are: mismatched voltages between the wire sets and the acceleration voltage of the instrument, which cause positive and negative peaks throughout mass spectra; insufficient deflection voltage, which reduces the intensity of real peaks and causes negative peaks that are spread across the entire mass range; and voltage errors as the wire sets return from their deflection voltage to their transmission value, which yield significant reductions in peak intensities, create artificial peaks throughout mass spectra, and broaden real peaks by causing positive peaks to grow in the bins adjacent to them. Because the magnitude of the modulation defects grows as the applied modulation voltage is increased, Bradbury-Nielson gates with finer wire spacing, and hence stronger effective fields for a given applied voltage, were produced and installed. Operating at 10 to 15 V where errors in the electronics are essentially absent, the most finely spaced gate (100 microm) yielded signal-to-noise ratios that were more than two times higher than those achieved with more widely spaced gates. As an alternative method for minimizing skewing effects, HT-TOFMS data were post processed using an exact knowledge of the modulation defects. Nonbinary matrices that mimic the actual encoding process were built by measuring voltage versus time traces and then translating these traces to transmission versus time. Use of these matrices in the deconvolution step led to marked improvements in spectral resolution but require full knowledge of the encoding defects.
View details for DOI 10.1016/S1044-0305(03)00006-0
View details for Web of Science ID 000181561400014
View details for PubMedID 12648935
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Flow injection analysis in a microfluidic format
ANALYTICAL CHEMISTRY
2003; 75 (4): 967-972
Abstract
A microfluidic flow injection analysis system has been designed and evaluated. The system incorporates within a single two-layer poly(dimethylsiloxane) monolith multiple pneumatically driven peristaltic pumps, an injection loop, a mixing column, and a transparent window for fluorescence detection. Central to this device is an injection system that mimics the operation of a standard six-port, two-way valve used in conventional liquid chromatography and flow injection experiments. Analyte and carrier solutions continuously flow through this injection system allowing for measurements and sample changes to be performed rapidly and simultaneously. Injection volumes of 1.25 nL generated peak area reproducibility of better than 3% relative standard deviation. The flow injection device was evaluated with fluorescent dyes and demonstrated a detection limit of 400 zmol for fluorescein. A rudimentary sample selection system allowed calibration curves to be rapidly produced, often in less than 10 min. The hydrolysis of fluorescein diphosphate by alkaline phosphatase demonstrates that chemical assays can be carried out with this device in a manner characterized by short analysis times and low sample consumption.
View details for DOI 10.1021/ac026112l
View details for Web of Science ID 000181073800038
View details for PubMedID 12622393
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Ultratrace kinetic measurements of the reduction of methylene blue
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2003; 125 (5): 1158-1159
Abstract
The kinetics of methylene blue reduction by ascorbic acid in acetonitrile was investigated by cavity ring-down spectroscopy. Because of our high sensitivity we were able to use very low concentrations (1-10 nM) of the dye. Under these conditions, we observed a second-order loss of dye as well as a competing back reaction with dissolved oxygen. The use of an inexpensive diode laser and a relatively simple setup should make ultratrace kinetic studies more accessible.
View details for Web of Science ID 000180713000025
View details for PubMedID 12553804
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Formation of carbon-carbon bonds in the photochemical alkylation of polycyclic aromatic hydrocarbons
ORIGINS OF LIFE AND EVOLUTION OF BIOSPHERES
2003; 33 (1): 17-35
Abstract
The reaction of polycyclic aromatic hydrocarbons (PAHs) with alkanes was examined in the presence of ultraviolet (UV) light under model prebiotic Earth and interstellar medium (ISM) conditions. We observed the formation of alkylated PAHs from a variety of PAHs and alkanes, which was caused by the absorption of UV light by the PAH molecule. Photoalkylation occurred in PAHs and alkanes in solution, in thin films in contact with simulated ocean water, and in matrices simulating ISM conditions. Photoalkylation occurred readily, with significant product yields within 5 h of irradiation. Because alkanes and PAHs are presumed to be part of the organic inventory in the ISM and on the early Earth, we propose that this photoalkylation reaction is a plausible pathway for the formation of carbon-carbon bonds in both these environments.
View details for Web of Science ID 000183130500002
View details for PubMedID 12967271
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Observation of beta(2)-adrenergic receptor activation using a photon counting histogram
BIOPHYSICAL SOCIETY. 2003: 123A
View details for Web of Science ID 000183123800599
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Single molecule fluorescent studies of immobilized beta(2)-adrenergic receptor
BIOPHYSICAL SOCIETY. 2003: 123A–124A
View details for Web of Science ID 000183123800600
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Dynamics of the simplest reaction of a carbon atom in a tetrahedral environment
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2003; 42 (42): 5227-5230
View details for DOI 10.1022/anie.200352642
View details for Web of Science ID 000186550800018
View details for PubMedID 14601179
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Rotationally resolved photoelectron spectra from vibrationally autoionizing Rydberg states of NO
Symposium on Dissociative Recombination of Molecular Ions with Electrons
KLUWER ACADEMIC/PLENUM PUBL. 2003: 289–299
View details for Web of Science ID 000188891600028
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Hadamard transform time-of-flight mass spectrometry: More signal, more of the time
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2003; 42 (1): 30-35
Abstract
Hadamard transform time-of-flight mass spectrometry (HT-TOF MS) is a type of mass analysis that was developed to couple continuous ion sources to the inherently pulsed nature of time-of-flight measurements. Unlike conventional TOF MS, the Hadamard transform method offers a duty cycle of 50%, with the possibility of extending it to 100%. Because it is a multiplexing technique, the attainable signal-to-noise ratio (SNR) is also significantly higher than that of conventional TOF MS. This review covers the basic principles behind HT-TOF MS. We illustrate, through examples, the source of the high-duty cycle and the increase in SNR. These features translate to a mass spectral storage rate that is the fastest among similar instruments, which enables its use as a detector for high-speed separations.
View details for Web of Science ID 000180458100006
View details for PubMedID 19757587
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Side group addition to the polycyclic aromatic hydrocarbon coronene by proton irradiation in cosmic ice analogs
ASTROPHYSICAL JOURNAL
2003; 582 (1): L25-L29
View details for Web of Science ID 000180000700005
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Programmable modification of cell adhesion and zeta potential in silica microchips
LAB ON A CHIP
2003; 3 (1): 5-10
Abstract
Spatial patterning of thin polyacrylamide films bonded to self-assembled monolayers on silica microchannels is described as a means for manipulating cell-adhesion and electroosmotic properties in microchips. Streaming potential measurements indicate that the zeta potential is reduced by at least two orders of magnitude at biological pH, and the adhesion of several kinds of cells is reduced by 80-100%. Results are shown for cover slides and in wet-etched silica microchannels. Because the polyacrylamide film is thin and transparent, this film is consistent with optical manipulation of cells and detection of cell contents. The spatial patterning technique is straightforward and has the potential to aid on-chip analysis of single adherent cells.
View details for DOI 10.1039/b210621n
View details for Web of Science ID 000181095300004
View details for PubMedID 15100798
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Toward sol-gel electrochromatographic separations on a chip
JOURNAL OF SEPARATION SCIENCE
2002; 25 (15-17): 1226-1230
View details for Web of Science ID 000179959200035
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Visualizing chemistry
JOURNAL OF CHEMICAL EDUCATION
2002; 79 (11): 1290-1291
View details for Web of Science ID 000178517000003
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Functional immobilization of a ligand-activated G-protein-coupled receptor
CHEMBIOCHEM
2002; 3 (10): 993-998
Abstract
G-protein-coupled receptors (GPCRs) mediate the majority of cellular responses to hormones and neurotransmitters. They are the largest family of receptors in the human genome and constitute the largest class of targets for drug discovery. To facilitate studies of GPCR activation and interactions with other proteins, we developed a simple method to immobilize a functional, detergent-solubilized GPCR on gold and glass surfaces. The beta(2) adrenergic receptor (beta(2)AR), a prototypical GPCR, was purified and labeled with a reporter fluorophore at a conformationally sensitive site. The detergent-soluble fluorescent beta(2)AR was immobilized through its amino-terminal FLAG epitope on a surface layered with biotinylated bovine serum albumin, avidin, and biotinylated M1 antibody. Agonist activation of the beta(2)AR was monitored in real time by fluorescence microscopy. This approach will make it possible to study conformational dynamics of single immobilized receptors and to generate arrays of functional GPCRs for novel high-throughput screening strategies.
View details for Web of Science ID 000178555900009
View details for PubMedID 12362365
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Coupled electrorotation of polymer microspheres for microfluidic sensing and mixing
ANALYTICAL CHEMISTRY
2002; 74 (19): 5099-5104
Abstract
We show that coupled electrorotation (CER) of microscopic particles using microfabricated electrodes can be used for localized sensing and mixing. The effective use of microelectromechanical systems and micro total analysis systems requires many types of control. These include the abilityto (1) manipulate objects within microchannels by noncontact means, (2) mix fluids, and (3) sense local chemical parameters. Coupled electrorotation, in which the interactions between induced electric dipoles of adjacent particles lead to particle rotation, addresses aspects of all three challenges simultaneously. CER is a simple means of controlling the rotation of dielectric objects using homogeneous external radio frequency electric fields. CER is sensitive to several chemical and physical parameters such as the solution conductivity, pH, and viscosity. As a step toward integrating CER devices into microfluidic systems, a simple chip was designed to induce local mixing and to detect local changes in salt concentration, pH, and viscosity.
View details for DOI 10.1021/ac0258599
View details for Web of Science ID 000178418100042
View details for PubMedID 12380836
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Side group addition to the polycyclic aromatic hydrocarbon coronene by ultraviolet photolysis in cosmic ice analogs
ASTROPHYSICAL JOURNAL
2002; 576 (2): 1115-1120
View details for Web of Science ID 000177804800046
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Capillary electrophoresis separation and native laser-induced fluorescence detection of metallotexaphrins
JOURNAL OF SEPARATION SCIENCE
2002; 25 (13): 819-824
View details for Web of Science ID 000178547800004
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Analysis of bimolecular interactions using a miniaturized surface plasmon resonance sensor
ANALYTICAL CHEMISTRY
2002; 74 (17): 4570-4576
Abstract
A commercially available miniaturized surface plasmon resonance sensor has been investigated for its applicability to biological interaction analysis. The sensor was found to exhibit excellent repeatability and linearity for high-refractive index solutions and good reproducibility for the binding of proteins. Its detection limit for the monoclonal antibody M1 was found to be 2.1 fmol, which corresponds to a surface concentration of 21 pg/mm2. Simple surface immobilization procedures relying on biotin/avidin or glycoprotein/lectin chemistry have been explored. Equilibrium dissociation constants for the binding of the FLAG peptide to its monoclonal antibody (M1) and for the binding of concanavalin A to a glycoprotein have been determined. The close agreement of these measurements with values obtained by surface fluorescence microscopy and fluorescence correlation spectroscopy helps to validate the use of this device. Thus, this sensor shows promise as an inexpensive, portable, and accurate tool for bioanalytical applications in laboratory and clinical settings.
View details for DOI 10.1021/ac025669y
View details for Web of Science ID 000177862800039
View details for PubMedID 12236371
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Temporally resolved cavity ring-down spectroscopy in a pulsed nitrogen plasma
APPLIED PHYSICS LETTERS
2002; 81 (8): 1408-1410
View details for DOI 10.1063/1.1500427
View details for Web of Science ID 000177351600014
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Channel-specific angular distributions of HCl and CH3 products from the reaction of atomic chlorine with stretch-excited methane
JOURNAL OF CHEMICAL PHYSICS
2002; 117 (7): 3232-3242
View details for DOI 10.1063/1.1493192
View details for Web of Science ID 000177202300028
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Spatial profiles of N-2(+) concentration in an atmospheric pressure nitrogen flow discharge
PLASMA SOURCES SCIENCE & TECHNOLOGY
2002; 11 (3): 248-253
View details for Web of Science ID 000178018900004
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Effect of laser lineshape on the quantitative analysis of cavity ring-down signals
LASER PHYSICS
2002; 12 (8): 1065-1072
View details for Web of Science ID 000177820400003
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Effect of preparatory conditions on the performance of photopolymerized sol-gel monoliths for capillary electrochromatography
International Symposium on High Performance Liquid Phase Separations and Related Techniques (HPLC Kyoto)
ELSEVIER SCIENCE BV. 2002: 45–51
Abstract
We prepared different photopolymerized sol-gel (PSG) columns by varying the amount of monomer (methacryloxypropyltrimethoxysilane), porogen (toluene) and catalyst (hydrochloric acid) in the reaction solution containing a photoinitiator (Irgacure 1800). The effects of these variations on the chromatographic behavior of the PSG columns were studied. All of the columns studied exhibited reversed-phase character. The concentration of hydrochloric acid was important for the rigidity of the columns, although it did not affect the separation property. The ratio of monomer solution to porogen was a critical factor in controlling the through-pore size and the surface area of PSG, which were found to significantly affect the separation properties, such as permeability, theoretical plate number, retention time, and separation efficiency, of a mixture of test analytes-thiourea, benzene, and naphthalene. There was no change in the retention order for the test analytes. Short separation times were achieved on PSG columns made from a 10% monomer stock solution and 90% porogen with 1 M hydrochloric acid. Mixtures of polycyclic aromatic hydrocarbons and alkylbenzenes were separated with theoretical plate numbers greater than 100 000 plates/m.
View details for Web of Science ID 000177061200006
View details for PubMedID 12186390
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Coupled electrorotation: Two proximate microspheres spin in registry with an AC electric field
CHEMPHYSCHEM
2002; 3 (5): 416-?
Abstract
We report a novel approach to micro- and nanoparticle rotation, uniting the fine translational control afforded by optical trapping with the flexibility and simplicity of dipole-field-induced coupled electrorotation (CER). Fluorescence imaging using a microparticle photopatterning technique was combined with optical trapping to quantify both the senses and speeds of rotation for individual pairs of particles. Laser tweezers allowed controlled positioning of a pair of particles within a dipole field while simultaneously providing an axis about which the particles rotated. The particle-particle interactions inherent in CER offer several distinct advantages compared with electrorotation in multipole fields. Results from several investigations highlight the utility of this approach, including quantification of rotation in spheres as small as 750 nm in diameter, observation of rotation rates as high as 1800 rpm, fabrication of coupled electrorotational "antigears", trapping and rotation of sphere dimers, and exploitation of the registry of sphere rotation to probe the dielectric properties of immobile objects.
View details for Web of Science ID 000175811800005
View details for PubMedID 12465501
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Stable isotope ratios using cavity ring-down spectroscopy: Determination of C-13/C-12 for carbon dioxide in human breath
ANALYTICAL CHEMISTRY
2002; 74 (9): 2003-2007
Abstract
We have constructed a cavity ring-down spectrometer employing a near-IR external cavity diode laser capable of measuring 13C/12C isotopic ratios in CO2 in human breath. The system, which has a demonstrated minimum detectable absorption loss of 3.2 x 10(-11) cm(-1) Hz(-1/2), determines the isotopic ratio of 13C16O16O/12C16O16O by measuring the intensities of rotationally resolved absorption features of each species. As in isotope ratio mass spectrometry (IRMS), the isotopic ratio of a sample is compared to that of a standard CO2 sample calibrated to the Pee Dee Belemnite scale and reported as the sample's delta13C value. Measurements of eight replicate CO2 samples standardized by IRMS and consisting of 5% CO2 in N2 at atmospheric pressure demonstrated a precision of 0.22/1000 for the technique. Delta13C values were also obtained for breath samples from individuals testing positive and negative for the presence of Helicobacter pylori, the leading cause of peptic ulcers in humans. This study demonstrates the ability of the instrument to obtain delta13C values in breath samples with sufficient precision to serve as a useful medical diagnostic.
View details for DOI 10.1021/ac025511d
View details for Web of Science ID 000175358800036
View details for PubMedID 12033299
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State-resolved differential and integral cross sections for the reaction H+D-2 -> HD(v '=3,j(')=0-7)+D at 1.64 eV collision energy
JOURNAL OF CHEMICAL PHYSICS
2002; 116 (15): 6634-6639
View details for DOI 10.1063/1.1462576
View details for Web of Science ID 000174767200027
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Hadamard transform time-of-flight mass spectrometry: A high-speed detector for capillary-format separations
ANALYTICAL CHEMISTRY
2002; 74 (7): 1611-1617
Abstract
This work demonstrates that with an intrinsic duty cycle of 50% and spectral storage speeds up to 277 spectra s(-1) Hadamard transform time-of-flight mass spectrometry (HT-TOFMS) is a promising detector for any capillary-format separation that can be coupled to MS by electrospray ionization. Complete resolution of the components of a nine-peptide standard was achieved by coupling pressurized-capillary electrophoresis (pCE) to HT-TOFMS. The addition of pressure to the separation capillary decreased analysis times and stabilized the electrospray ionization source. Pulsed-pressurized injection of reserpine was used to experimentally simulate narrower peaks than those obtained in the pCE. HT-TOFMS was able to sample peaks having widths in the millisecond range.
View details for DOI 10.1021/ac015673u
View details for Web of Science ID 000174841600031
View details for PubMedID 12033252
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Direct monitoring of absorption in solution by cavity ring-down spectroscopy
ANALYTICAL CHEMISTRY
2002; 74 (7): 1741-1743
Abstract
Cavity ring-down spectroscopy is applied to the liquid phase by placing the target solution directly into the optical cavity. We demonstrate that solutions in the cavity can be stirred and more importantly monitored in a flow. We report a minimum detectable absorption of 10(-6) cm(-1) for a range of organic solvents. This detection limit corresponds to picomolar concentrations for strong absorbers.
View details for DOI 10.1021/ac011103i
View details for Web of Science ID 000174841600050
View details for PubMedID 12033270
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Observation and interpretation of a time-delayed mechanism in the hydrogen exchange reaction
NATURE
2002; 416 (6876): 67-70
Abstract
Extensive theoretical and experimental studies have shown the hydrogen exchange reaction H+H2 --> H2+H to occur predominantly through a 'direct recoil' mechanism: the H--H bonds break and form concertedly while the system passes straight over a collinear transition state, with recoil from the collision causing the H2 product molecules to scatter backward. Theoretical predictions agree well with experimental observations of this scattering process. Indirect exchange mechanisms involving H3 intermediates have been suggested to occur as well, but these are difficult to test because bimolecular reactions cannot be studied by the femtosecond spectroscopies used to monitor unimolecular reactions. Moreover, full quantum simulations of the time evolution of bimolecular reactions have not been performed. For the isotopic variant of the hydrogen exchange reaction, H+D2 --> HD+D, forward scattering features observed in the product angular distribution have been attributed to possible scattering resonances associated with a quasibound collision complex. Here we extend these measurements to a wide range of collision energies and interpret the results using a full time-dependent quantum simulation of the reaction, thus showing that two different reaction mechanisms modulate the measured product angular distribution features. One of the mechanisms is direct and leads to backward scattering, the other is indirect and leads to forward scattering after a delay of about 25 femtoseconds.
View details for Web of Science ID 000174211600038
View details for PubMedID 11882892
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Irradiation of dye-doped microspheres with a stronqly focused laser beam results in alignment upon optical trapping
NANO LETTERS
2002; 2 (3): 207-210
View details for DOI 10.1021/nl015632d
View details for Web of Science ID 000174640900008
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Electroosmotic flow pumps with polymer frits
SENSORS AND ACTUATORS B-CHEMICAL
2002; 82 (2-3): 209-212
View details for Web of Science ID 000174483000010
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Genetic screening using the colour change of a PNA-DNA hybrid-binding cyanine dye
NUCLEIC ACIDS RESEARCH
2002; 30 (2)
Abstract
As the relationship between human genes and various malfunctions and diseases becomes revealed at an ever-increasing pace, the need arises for the development of rapid genetic screening methods for diagnostic purposes. Genetic diseases show great diversity. Some are caused by a few characteristic localised mutations, while others arise from a large number of variations. Hence, it is unlikely that a single, general diagnostic method that applies to all cases will ever exist. Instead, a combination of methods is frequently applied. Here we propose the use of a dramatic colour change that a cyanine dye, 3,3'-diethylthiadicarbocyanine, displays upon binding to DNA-PNA duplexes. This method could become an inexpensive, fast and simple genetic screening test by visual inspection, with no need for complicated equipment. Our results demonstrate that this diagnostic method may be sufficiently sensitive to discriminate between even a fully complementary and a single mutation DNA sequence.
View details for Web of Science ID 000173551200027
View details for PubMedID 11788729
View details for PubMedCentralID PMC99842
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Scattering resonances in the simplest chemical reaction
ANNUAL REVIEW OF PHYSICAL CHEMISTRY
2002; 53: 67-99
Abstract
Recent studies of state-resolved angular distributions show the participation of reactive scattering resonances in the simplest chemical reaction. This review is intended for those who wish to learn about the state-of-the-art in the study of the H + H2 reaction family that has made this breakthrough possible. This review is also intended for those who wish to gain insight into the nature of reactive scattering resonances. Following a tour across several fields of physics and chemistry where the concept of resonance has been crucial for the understanding of new phenomena, we offer an operational definition and taxonomy of reactive scattering resonances. We introduce simple intuitive models to illustrate each resonance type. We focus next on the last decade of H + H2 reaction dynamics. Emphasis is placed on the various experimental approaches that have been applied to the search for resonance behavior in the H + H2 reaction family. We conclude by sketching the road ahead in the study of H + H2 reactive scattering resonances.
View details for DOI 10.1146/annurev.physchem.53.091001.194554
View details for Web of Science ID 000176264900005
View details for PubMedID 11972003
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Fluorescent studies of the beta(2) adrenergic receptor labeled at a conformational sensitive site
BIOPHYSICAL SOCIETY. 2002: 354A
View details for Web of Science ID 000173252701740
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Bonded-phase photopolymerized sol-gel monoliths for reversed phase capillary electrochromatography
JOURNAL OF SEPARATION SCIENCE
2002; 25 (1-2): 3-9
View details for Web of Science ID 000173610600002
- Observation of Scattering Resonances in the H+D2 Reaction: Direct Probe of the HD2 Transition-State Geometry Femtochemistry And Femtobiology: Ultrafast Dynamics in Molecular Science World Scientific Press. 2002: 61–72
- Analysis of Biomolecular Interactions Using a Miniaturized Plasmon Resonance Sensor Anal. Chem. 2002; 74: 4570-4576
- Electroosmotic Flow Pumps with Large Flow Rates Sensors & Actuators B 2002; 82: 209-212
- Irradiation of Dye-Doped Microspheres with a Strongly Focused Laser Beam Results in Alignment upon Optical Trapping Nano Letters 2002; 2 (3): 207-210
- Formation of Carbon-Carbon bonds in Photochemical Alkylation of Polycyclic Aromatic Hydrocarbons The Origins and Early Evolution of Life 2002; 139
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Microscale detection of polychlorinated biphenyls using two-step laser mass spectrometry
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
2001; 212 (1-3): 41-48
View details for Web of Science ID 000173003600007
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Vibrational control in the reaction of methane with atomic chlorine
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2001; 123 (50): 12714-12715
View details for DOI 10.1021/ja017180c
View details for Web of Science ID 000172745300046
View details for PubMedID 11741451
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Novel method for the production of finely spaced Bradbury-Nielson gates
REVIEW OF SCIENTIFIC INSTRUMENTS
2001; 72 (12): 4354-4357
View details for Web of Science ID 000172387400005
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Effect of sequence length, sequence frequency, and data acquisition rate on the performance of a Hadamard transform time-of-flight mass spectrometer
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
2001; 12 (12): 1302-1311
Abstract
Various factors influencing the performance of a Hadamard transform time-of-flight mass spectrometer (HT-TOFMS) have been investigated. Using a nitrogen corona discharge to produce an ion stream of N2+, N3+, and N4+, it is found for spectra containing only N4+ that the signal-to-noise ratio (SNR) closely approaches the value calculated from the ion background by assuming that the ion background follows a Poisson distribution. In contrast, for a more intense beam containing N2+, N3+, and N4+, the SNR is less than its theoretical value because of the appearance of discrete spikes in the mass spectrum caused by deviations in the actual modulation sequence from the ideal one. These spikes can be reduced, however, by decreasing the modulation voltage. Under these optimized conditions, the pseudo-random sequence length is varied to understand how it alters SNR, mass resolution, and scan speed. When the length of the pseudo-random sequence is doubled, the SNR increases by the square root of 2 while the time necessary to record a mass spectrum also doubles. Mass resolution can be varied between 500 and 1200 at m/z = 609 as the sequence length, modulation speed (10 MHz, 25 MHz), and acquisition rate (up to 50 MHz) are changed. Scan speeds of 6000 passes per s can be obtained using a sequence containing 4095 elements modulated at 25 MHz. The capability to tailor the HT-TOFMS to increase the scan speed and resolution with a constant 50% duty cycle makes the technique extremely appealing as a mass analyzer for measuring rapid changes in the composition of an ion stream.
View details for Web of Science ID 000172644400009
View details for PubMedID 11766757
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Strategy for on-line preconcentration in chromatographic separations
ANALYTICAL CHEMISTRY
2001; 73 (22): 5539-5543
Abstract
In chromatographic separations, the heights of peaks are proportional to the concentrations of sample components present in an injected mixture. In general, an increase in the peak height cannot be achieved by simply increasing the injection time or the sample plug length. An exception occurs if some form of on-line preconcentration is possible. We present a new strategy for achieving on-line preconcentration by the use of a porous chromatographic material that acts as a solid-phase extractor as well as a stationary-phase separator. We are able to realize significant on-line preconcentration using capillary columns filled with a photopolymerized sol-gel (PSG). More than 2-cm plugs of sample solution can be loaded into the capillary and concentrated using a running buffer that is the same as the injection buffer (to avoid solvent gradient effects). As a demonstration, mixtures of three different polycyclic aromatic hydrocarbons, eight different alkyl phenyl ketones, and five different peptides in solutions of aqueous acetonitrile have been injected onto the PSG column and separated by capillary electrochromatography. The preconcentration is marked in terms of peak heights, with up to 100-fold increase for the PAH mixture, 30-fold for the alkyl phenyl ketone mixture, and 20-fold for the peptide mixture. Preconcentration takes place because of the high mass-transfer rates possible in the highly porous structure, and the extent of preconcentration follows the retention factor k for a given analyte.
View details for DOI 10.1021/ac015522r
View details for Web of Science ID 000172209400027
View details for PubMedID 11816585
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On-line preconcentration in capillary electrochromatography using a porous monolith together with solvent gradient and sample stacking
ANALYTICAL CHEMISTRY
2001; 73 (22): 5557-5563
Abstract
Preconcentration effects of solvent gradient and sample stacking are investigated on a photopolymerized sol-gel (PSG) in capillary electrochromatography. The porous PSG monolith has a high mass-transfer rate. This characteristic promotes preconcentration of dilute samples. Plugs of samples more than 2 cm in length prepared in the separation solution (nongradient condition) are injected onto the PSG column. The extent of preconcentration is quite significant, showing up to a 100-fold increase in peak heights of the separated analytes. Even larger preconcentrations are achieved under gradient conditions by dissolving the sample in a matrix with a higher concentration of noneluting solvent (water). For eight alkyl phenyl ketones and four polycyclic aromatic hydrocarbons that serve as neutral test analytes, improvements in peak heights obtained under gradient conditions can be more than a 1000-fold. Indeed, injection of a 91.2-cm plug, which is more than 3 times the total length of the capillary, was possible with only a minor loss in resolution. Five peptides serve as charged test analytes. Nongradient conditions in which the sample is hydrodynamically injected onto the PSG column show sizable preconcentration because of sample stacking. The use of a solvent gradient with the same ionic strength, however, does not appear to have practical value because of destacking caused by the changing organic composition that affects the conductivity. As an alternative preconcentration method, we demonstrate that electric field-enhanced sample injection on the PSG yielded up to a 1000-fold improvement in detection sensitivity for the test peptides.
View details for Web of Science ID 000172209400030
View details for PubMedID 11816588
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N-2 product internal-state distributions for the steady-state reactions of NO with H-2 and NH3 on the Pt(100) surface
JOURNAL OF PHYSICAL CHEMISTRY B
2001; 105 (37): 8725-8728
View details for Web of Science ID 000171032600012
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Forward scattering in the H+D-2 -> HD+D reaction: Comparison between experiment and theoretical predictions
JOURNAL OF CHEMICAL PHYSICS
2001; 115 (10): 4534-4545
View details for Web of Science ID 000170647600015
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Comparison of microprobe two-step laser desorption/laser ionization mass spectrometry and gas chromatography/mass spectrometry studies of polycyclic aromatic hydrocarbons in ancient terrestrial rocks
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
2001; 12 (9): 989-1001
View details for Web of Science ID 000171108600002
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Photopolymerized sol-gel monoliths for capillary electrochromatography
ANALYTICAL CHEMISTRY
2001; 73 (16): 3921-3926
Abstract
A solution of methacryloxypropyltrimethoxysilane in the presence of an acid catalyst, water, toluene, and a photoinitiator was irradiated at 365 nm for 5 min in a 75-microm i.d. capillary to prepare a porous monolithic sol-gel column by a one-step, in situ, process. The photopolymerized sol-gel (PSG) column shows reversed-phase behavior. Using this column, a variety of low-molecular-weight neutral compounds, including polycyclic aromatic hydrocarbons, alkyl benzenes, alkyl phenyl ketones, and steroids are separated from mixtures. Various different operational parameters, such as buffer composition, field strength, and column temperature, were varied to assess their influence on column performance. Use of PSG as a stationary phase for a pressure-driven separation is also demonstrated.
View details for DOI 10.1006/ac0100749
View details for Web of Science ID 000170482800019
View details for PubMedID 11534717
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Photopolymerized sol-gel frits for packed columns in capillary electrochromatography
14th International Symposium on Microscale Separations and Analysis
ELSEVIER SCIENCE BV. 2001: 187–95
Abstract
Porous sol-gel frits are fabricated in a capillary column by filling it with a solution of 3-(trimethoxysilyl)propyl methacrylate, hydrochloric acid, water, toluene (porogen), and a photoinitiator (Irgacure 1800) and exposing it to UV light at 365 nm for 5 min. The separation column (30 cm x 75 microm I.D.) contains between the inlet and outlet frits a 15-cm packed segment filled with 5-microm silica particles modified with the chiral compound (S)-N-3,5-dinitrobenzoyl-1-naphthylglycine. A detection window (1 mm long) is placed immediately after the outlet frit. To demonstrate the performance of this chiral separation column, mixtures of 16 different amino acids (three of which are not naturally occurring) derivatized with the fluorogenic reagent 4-fluoro-7-nitro-2,1,3-benzoxadiazole were separated by capillary chromatography. The enantiomeric separation of the column results in a resolution ranging from 1.21 to 8.29, and a plate height ranging from 8.7 to 39 microm.
View details for Web of Science ID 000170359200018
View details for PubMedID 11521865
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Electrophoretron: a new method for enhancing resolution in electrokinetic separations
14th International Symposium on Microscale Separations and Analysis
ELSEVIER SCIENCE BV. 2001: 53–58
Abstract
Two capillaries, each of which have different surface preparations on their inside walls, are joined together to form a closed loop, and electrodes are placed inside the two capillaries. When the loop is filled with liquid and a potential difference is applied between the two electrodes, a circulating flow of liquid is established inside the loop because the resistance to flow is unequal in going from one electrode to another in a clockwise versus a counterclockwise direction. Consequently, a sample injected into this device, which we call an electrophoretron, repeatedly circulates between the two electrodes and the capillary separation column becomes effectively one of unlimited length. On each cycle the separation between analytes with different mobilities increases, thus enhancing resolution of analytes having nearly the same mobilities. The operation of a prototype electrophoretron is demonstrated.
View details for Web of Science ID 000170359200005
View details for PubMedID 11521906
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Single-molecule spectroscopy of the beta(2) adrenergic receptor: Observation of conformational substates in a membrane protein
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2001; 98 (15): 8469-8474
Abstract
Single-molecule studies of the conformations of the intact beta(2) adrenergic receptor were performed in solution. Photon bursts from the fluorescently tagged adrenergic receptor in a micelle were recorded. A photon-burst algorithm and a Poisson time filter were implemented to characterize single molecules diffusing across the probe volume of a confocal microscope. The effects of molecular diffusion and photon number fluctuations were deconvoluted by assuming that Poisson distributions characterize the molecular occupation and photon numbers. Photon-burst size histograms were constructed, from which the source intensity distributions were extracted. Different conformations of the beta(2) adrenergic receptor cause quenching of the bound fluorophore to different extents and hence produce different photon-burst sizes. An analysis of the photon-burst histograms shows that there are at least two distinct substates for the native adrenergic membrane receptor. This behavior is in contrast to one peak observed for the dye molecule, rhodamine 6G. We test the reliability and robustness of the substate number determination by investigating the application of different binning criteria. Conformational changes associated with agonist binding result in a marked change in the distribution of photon-burst sizes. These studies provide insight into the conformational heterogeneity of G protein-coupled receptors in the presence and absence of a bound agonist.
View details for Web of Science ID 000169967000049
View details for PubMedID 11438704
View details for PubMedCentralID PMC37459
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Vibrational and collisional energy effects in the reaction of ammonia ions with methylamine
JOURNAL OF CHEMICAL PHYSICS
2001; 115 (1): 124-132
View details for Web of Science ID 000169385300014
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Comparison of near-threshold reactivity of ground-state and spin-orbit excited chlorine atoms with methane
JOURNAL OF CHEMICAL PHYSICS
2001; 115 (1): 179-183
View details for Web of Science ID 000169385300021
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Cavity ring-down spectroscopy of CH and CD radicals in a diamond thin film chemical vapor deposition reactor
APPLIED PHYSICS A-MATERIALS SCIENCE & PROCESSING
2001; 73 (1): 27-33
View details for Web of Science ID 000169584100003
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Semipreparative capillary electrochromatography
ANALYTICAL CHEMISTRY
2001; 73 (9): 1987-1992
Abstract
Capillaries with inner diameters of 550 microm have successfully been packed with 1.5-microm octadecyl silica particles using frits made of macroporous polymers by the UV photopolymerization of a solution of glycidyl methacrylate and trimethylolpropane trimethacrylate. This type of frit is found superior to one made of low-melting point poly(styrene-co-divinylbenzene) beads. Bubble formation is not observed to occur within these capillary columns under our experimental conditions. Separations can be achieved with sample injection volumes as high as 1 microL. To demonstrate its semipreparative use, a mixture of 500 nL of taxol (20 mM) and its precursor, baccatin III (30 mM), is separated using such a column with a Tris buffer.
View details for Web of Science ID 000168519800017
View details for PubMedID 11354480
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Low temperature ice photochemistry as a source of meteoritic and cometary organics.
AMER CHEMICAL SOC. 2001: U540–U540
View details for Web of Science ID 000168824703564
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Distribution of rovibrational product states for the "prompt" reaction H+D-2(nu=0,j=0-4) -> HD(nu '=1,2,j ')+D near 1.6 eV collision energy
JOURNAL OF PHYSICAL CHEMISTRY A
2001; 105 (11): 2228-2233
View details for DOI 10.1021/jp0027288
View details for Web of Science ID 000167632400013
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Bounce-by-bounce cavity ring-down spectroscopy: Femtosecond temporal imaging
CHEMPHYSCHEM
2001; 2 (2): 118-?
Abstract
A time microscope (100× magnification) allows light pulses exiting an optical cavity to be viewed one at a time. A linearly chirped Gaussian pulse is mixed in a nonlinear crystal with the dispersed input waveform; the up-converted light is sent onto an output dispersive network. The resulting temporal image is recorded both with a streak camera and with a spectrometer.
View details for Web of Science ID 000168286600005
View details for PubMedID 23696438
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Nanoengineered structures for holding and manipulating liposomes and cells
ANALYTICAL CHEMISTRY
2001; 73 (4): 787-791
Abstract
We describe the fabrication of nanoengineered holding pipets with concave seating surfaces and fine pressure control. These pipets were shown to exhibit exceptional stability in capturing, transporting, and releasing single cells and liposomes 1-12 microm in diameter, which opens previously inaccessible avenues of research. Three specific examples demonstrated the utility and versatility of this manipulation system. In the first, carboxyrhodamine was selectively incorporated into individual cells by electroporation, after which nearly all the medium (hundreds of microliters) surrounding the docked and tagged cells was rapidly exchanged (in seconds) and the cells were subsequently probed by laser-induced fluorescence (LIF). In the second study, a single liposome containing carboxyrhodamine was transported to a dye-free solution using a transfer pipet, docked to a holding pipet, and held firmly during physical agitation and interrogation by LIF. In the third study, pairs of liposomes were positioned between two microelectrodes, held in contact, and selectively electrofused and the resulting liposomes undocked intact.
View details for DOI 10.1021/ac001020m
View details for Web of Science ID 000167076700010
View details for PubMedID 11248893
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Microprobe laser mass spectrometry studies of polycyclic aromatic hydrocarbon distributions on harbor sediments and coals
ISRAEL JOURNAL OF CHEMISTRY
2001; 41 (2): 105-110
View details for Web of Science ID 000172703700005
- On the One Hand But Not the Other: The Challenge of the Origin and Survival of Homochirality in Prebiotic Chemistry Chemistry for the 21st Century edited by Keinan, E., Schechter, I. Wiley-VCH Gmbh: Weinheim, Germany. 2001: 175–208
- Confining and Probing Single Molecules in Synthetic Liposomes Single-Molecule Spectroscopy: Nobel Conference Lectures edited by Rigler, R., Orrit, M., Basche, T. Springer-Verlag: Berlin Heidelberg. 2001
- Nanoforms: A new type of protein-associated mineralization GEOCHIMICA ET COSMOCHIMICA ACTA 2001; 65 (1): 63-74