Lei Liu
Masters Student in Management Science and Engineering, admitted Autumn 2020
All Publications
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Nuclear Resonance Vibrational Spectroscopy Definition of O-2 Intermediates in an Extradiol Dioxygenase: Correlation to Crystallography and Reactivity
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2018; 140 (48): 16495–513
View details for DOI 10.1021/jacs.8b06517
View details for Web of Science ID 000452693800021
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Nuclear Resonance Vibrational Spectroscopy Definition of O2 Intermediates in an Extradiol Dioxygenase: Correlation to Crystallography and Reactivity.
Journal of the American Chemical Society
2018
Abstract
The extradiol dioxygenases are a large subclass of mononuclear nonheme Fe enzymes that catalyze the oxidative cleavage of catechols distal to their OH groups. These enzymes are important in bioremediation, and there has been significant interest in understanding how they activate O2. The extradiol dioxygenase homoprotocatechuate 2,3-dioxygenase (HPCD) provides an opportunity to study this process, as two O2 intermediates have been trapped and crystallographically defined using the slow substrate 4-nitrocatechol (4NC): a side-on Fe-O2-4NC species and a Fe-O2-4NC peroxy bridged species. Also with 4NC, two solution intermediates have been trapped in the H200N variant, where H200 provides a second-sphere hydrogen bond in the wild-type enzyme. While the electronic structure of these solution intermediates has been defined previously as FeIII-superoxo-catecholate and FeIII-peroxy-semiquinone, their geometric structures are unknown. Nuclear resonance vibrational spectroscopy (NRVS) is an important tool for structural definition of nonheme Fe-O2 intermediates, as all normal modes with Fe displacement have intensity in the NRVS spectrum. In this study, NRVS is used to define the geometric structure of the H200N-4NC solution intermediates in HPCD as an end-on FeIII-superoxo-catecholate and an end-on FeIII-hydroperoxo-semiquinone. Parallel calculations are performed to define the electronic structures and protonation states of the crystallographically defined wild-type HPCD-4NC intermediates, where the side-on intermediate is found to be a FeIII-hydroperoxo-semiquinone. The assignment of this crystallographic intermediate is validated by correlation to the NRVS data through computational removal of H200. While the side-on hydroperoxo semiquinone intermediate is computationally found to be nonreactive in peroxide bridge formation, it is isoenergetic with a superoxo catecholate species that is competent in performing this reaction. This study provides insight into the relative reactivities of FeIII-superoxo and FeIII-hydroperoxo intermediates in nonheme Fe enzymes and into the role H200 plays in facilitating extradiol catalysis.
View details for PubMedID 30418018
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NRVS Studies of the Peroxide Shunt Intermediate in a Rieske Dioxygenase and Its Relation to the Native Fe-II O-2 Reaction
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2018; 140 (16): 5544–59
Abstract
The Rieske dioxygenases are a major subclass of mononuclear nonheme iron enzymes that play an important role in bioremediation. Recently, a high-spin FeIII-(hydro)peroxy intermediate (BZDOp) has been trapped in the peroxide shunt reaction of benzoate 1,2-dioxygenase. Defining the structure of this intermediate is essential to understanding the reactivity of these enzymes. Nuclear resonance vibrational spectroscopy (NRVS) is a recently developed synchrotron technique that is ideal for obtaining vibrational, and thus structural, information on Fe sites, as it gives complete information on all vibrational normal modes containing Fe displacement. In this study, we present NRVS data on BZDOp and assign its structure using these data coupled to experimentally calibrated density functional theory calculations. From this NRVS structure, we define the mechanism for the peroxide shunt reaction. The relevance of the peroxide shunt to the native FeII/O2 reaction is evaluated. For the native FeII/O2 reaction, an FeIII-superoxo intermediate is found to react directly with substrate. This process, while uphill thermodynamically, is found to be driven by the highly favorable thermodynamics of proton-coupled electron transfer with an electron provided by the Rieske [2Fe-2S] center at a later step in the reaction. These results offer important insight into the relative reactivities of FeIII-superoxo and FeIII-hydroperoxo species in nonheme Fe biochemistry.
View details for PubMedID 29618204
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Peroxide Activation for Electrophilic Reactivity by the Binuclear Non-heme Iron Enzyme AurF.
Journal of the American Chemical Society
2017; 139 (20): 7062-7070
Abstract
Binuclear non-heme iron enzymes activate O2 for diverse chemistries that include oxygenation of organic substrates and hydrogen atom abstraction. This process often involves the formation of peroxo-bridged biferric intermediates, only some of which can perform electrophilic reactions. To elucidate the geometric and electronic structural requirements to activate peroxo reactivity, the active peroxo intermediate in 4-aminobenzoate N-oxygenase (AurF) has been characterized spectroscopically and computationally. A magnetic circular dichroism study of reduced AurF shows that its electronic and geometric structures are poised to react rapidly with O2. Nuclear resonance vibrational spectroscopic definition of the peroxo intermediate formed in this reaction shows that the active intermediate has a protonated peroxo bridge. Density functional theory computations on the structure established here show that the protonation activates peroxide for electrophilic/single-electron-transfer reactivity. This activation of peroxide by protonation is likely also relevant to the reactive peroxo intermediates in other binuclear non-heme iron enzymes.
View details for DOI 10.1021/jacs.7b02997
View details for PubMedID 28457126
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Nuclear Resonance Vibrational Spectroscopic Definition of Peroxy Intermediates in Nonheme Iron Sites.
Journal of the American Chemical Society
2016; 138 (43): 14294-14302
Abstract
Fe(III)-(hydro)peroxy intermediates have been isolated in two classes of mononuclear nonheme Fe enzymes that are important in bioremediation: the Rieske dioxygenases and the extradiol dioxygenases. The binding mode and protonation state of the peroxide moieties in these intermediates are not well-defined, due to a lack of vibrational structural data. Nuclear resonance vibrational spectroscopy (NRVS) is an important technique for obtaining vibrational information on these and other intermediates, as it is sensitive to all normal modes with Fe displacement. Here, we present the NRVS spectra of side-on Fe(III)-peroxy and end-on Fe(III)-hydroperoxy model complexes and assign these spectra using calibrated DFT calculations. We then use DFT calculations to define and understand the changes in the NRVS spectra that arise from protonation and from opening the Fe-O-O angle. This study identifies four spectroscopic handles that will enable definition of the binding mode and protonation state of Fe(III)-peroxy intermediates in mononuclear nonheme Fe enzymes. These structural differences are important in determining the frontier molecular orbitals available for reactivity.
View details for PubMedID 27726349
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Geometric and electronic structure of the Mn(IV)Fe(III) cofactor in class Ic ribonucleotide reductase: correlation to the class Ia binuclear non-heme iron enzyme.
Journal of the American Chemical Society
2013; 135 (46): 17573-17584
Abstract
The class Ic ribonucleotide reductase (RNR) from Chlamydia trachomatis (Ct) utilizes a Mn/Fe heterobinuclear cofactor, rather than the Fe/Fe cofactor found in the β (R2) subunit of the class Ia enzymes, to react with O2. This reaction produces a stable Mn(IV)Fe(III) cofactor that initiates a radical, which transfers to the adjacent α (R1) subunit and reacts with the substrate. We have studied the Mn(IV)Fe(III) cofactor using nuclear resonance vibrational spectroscopy (NRVS) and absorption (Abs)/circular dichroism (CD)/magnetic CD (MCD)/variable temperature, variable field (VTVH) MCD spectroscopies to obtain detailed insight into its geometric/electronic structure and to correlate structure with reactivity; NRVS focuses on the Fe(III), whereas MCD reflects the spin-allowed transitions mostly on the Mn(IV). We have evaluated 18 systematically varied structures. Comparison of the simulated NRVS spectra to the experimental data shows that the cofactor has one carboxylate bridge, with Mn(IV) at the site proximal to Phe127. Abs/CD/MCD/VTVH MCD data exhibit 12 transitions that are assigned as d-d and oxo and OH(-) to metal charge-transfer (CT) transitions. Assignments are based on MCD/Abs intensity ratios, transition energies, polarizations, and derivative-shaped pseudo-A term CT transitions. Correlating these results with TD-DFT calculations defines the Mn(IV)Fe(III) cofactor as having a μ-oxo, μ-hydroxo core and a terminal hydroxo ligand on the Mn(IV). From DFT calculations, the Mn(IV) at site 1 is necessary to tune the redox potential to a value similar to that of the tyrosine radical in class Ia RNR, and the OH(-) terminal ligand on this Mn(IV) provides a high proton affinity that could gate radical translocation to the α (R1) subunit.
View details for DOI 10.1021/ja409510d
View details for PubMedID 24131208
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Geometric and Electronic Structure of the Mn(IV)Fe(III) Cofactor in Class Ic Ribonucleotide Reductase: Correlation to the Class Ia Binuclear Non-Heme Iron Enzyme.
Journal of the American Chemical Society
2013; 135 (46): 17573-17584
Abstract
The class Ic ribonucleotide reductase (RNR) from Chlamydia trachomatis (Ct) utilizes a Mn/Fe heterobinuclear cofactor, rather than the Fe/Fe cofactor found in the β (R2) subunit of the class Ia enzymes, to react with O2. This reaction produces a stable Mn(IV)Fe(III) cofactor that initiates a radical, which transfers to the adjacent α (R1) subunit and reacts with the substrate. We have studied the Mn(IV)Fe(III) cofactor using nuclear resonance vibrational spectroscopy (NRVS) and absorption (Abs)/circular dichroism (CD)/magnetic CD (MCD)/variable temperature, variable field (VTVH) MCD spectroscopies to obtain detailed insight into its geometric/electronic structure and to correlate structure with reactivity; NRVS focuses on the Fe(III), whereas MCD reflects the spin-allowed transitions mostly on the Mn(IV). We have evaluated 18 systematically varied structures. Comparison of the simulated NRVS spectra to the experimental data shows that the cofactor has one carboxylate bridge, with Mn(IV) at the site proximal to Phe127. Abs/CD/MCD/VTVH MCD data exhibit 12 transitions that are assigned as d-d and oxo and OH(-) to metal charge-transfer (CT) transitions. Assignments are based on MCD/Abs intensity ratios, transition energies, polarizations, and derivative-shaped pseudo-A term CT transitions. Correlating these results with TD-DFT calculations defines the Mn(IV)Fe(III) cofactor as having a μ-oxo, μ-hydroxo core and a terminal hydroxo ligand on the Mn(IV). From DFT calculations, the Mn(IV) at site 1 is necessary to tune the redox potential to a value similar to that of the tyrosine radical in class Ia RNR, and the OH(-) terminal ligand on this Mn(IV) provides a high proton affinity that could gate radical translocation to the α (R1) subunit.
View details for DOI 10.1021/ja409510d
View details for PubMedID 24131208
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Geometric and Electronic Structure Contributions to Function in Non-heme Iron Enzymes
ACCOUNTS OF CHEMICAL RESEARCH
2013; 46 (11): 2725-2739
Abstract
Mononuclear non-heme Fe (NHFe) enzymes play key roles in DNA repair, the biosynthesis of antibiotics, the response to hypoxia, cancer therapy, and many other biological processes. These enzymes catalyze a diverse range of oxidation reactions, including hydroxylation, halogenation, ring closure, desaturation, and electrophilic aromatic substitution (EAS). Most of these enzymes use an Fe(II) site to activate dioxygen, but traditional spectroscopic methods have not allowed researchers to insightfully probe these ferrous active sites. We have developed a methodology that provides detailed geometric and electronic structure insights into these NHFe(II) active sites. Using these data, we have defined a general mechanistic strategy that many of these enzymes use: they control O2 activation (and limit autoxidation and self-hydroxylation) by allowing Fe(II) coordination unsaturation only in the presence of cosubstrates. Depending on the type of enzyme, O2 activation either involves a 2e(-) reduced Fe(III)-OOH intermediate or a 4e(-) reduced Fe(IV)═O intermediate. Nuclear resonance vibrational spectroscopy (NRVS) has provided the geometric structure of these intermediates, and magnetic circular dichroism (MCD) has defined the frontier molecular orbitals (FMOs), the electronic structure that controls reactivity. This Account emphasizes that experimental spectroscopy is critical in evaluating the results of electronic structure calculations. Therefore these data are a key mechanistic bridge between structure and reactivity. For the Fe(III)-OOH intermediates, the anticancer drug activated bleomycin (BLM) acts as the non-heme Fe analog of compound 0 in heme (e.g., P450) chemistry. However BLM shows different reactivity: the low-spin (LS) Fe(III)-OOH can directly abstract a H atom from DNA. The LS and high-spin (HS) Fe(III)-OOHs have fundamentally different transition states. The LS transition state goes through a hydroxyl radical, but the HS transition state is activated for EAS without O-O cleavage. This activation is important in one class of NHFe enzymes that utilizes a HS Fe(III)-OOH intermediate in dioxygenation. For Fe(IV)═O intermediates, the LS form has a π-type FMO activated for attack perpendicular to the Fe-O bond. However, the HS form (present in the NHFe enzymes) has a π FMO activated perpendicular to the Fe-O bond and a σ FMO positioned along the Fe-O bond. For the NHFe enzymes, the presence of π and σ FMOs enables enzymatic control in determining the type of reactivity: EAS or H-atom extraction for one substrate with different enzymes and halogenation or hydroxylation for one enzyme with different substrates.
View details for DOI 10.1021/ar400149m
View details for Web of Science ID 000327360800037
View details for PubMedID 24070107
View details for PubMedCentralID PMC3905672
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Elucidation of the Fe(IV)=O intermediate in the catalytic cycle of the halogenase SyrB2
NATURE
2013; 499 (7458): 320-?
Abstract
Mononuclear non-haem iron (NHFe) enzymes catalyse a broad range of oxidative reactions, including halogenation, hydroxylation, ring closure, desaturation and aromatic ring cleavage reactions. They are involved in a number of biological processes, including phenylalanine metabolism, the production of neurotransmitters, the hypoxic response and the biosynthesis of secondary metabolites. The reactive intermediate in the catalytic cycles of these enzymes is a high-spin S = 2 Fe(IV)=O species, which has been trapped for a number of NHFe enzymes, including the halogenase SyrB2 (syringomycin biosynthesis enzyme 2). Computational studies aimed at understanding the reactivity of this Fe(IV)=O intermediate are limited in applicability owing to the paucity of experimental knowledge about its geometric and electronic structure. Synchrotron-based nuclear resonance vibrational spectroscopy (NRVS) is a sensitive and effective method that defines the dependence of the vibrational modes involving Fe on the nature of the Fe(IV)=O active site. Here we present NRVS structural characterization of the reactive Fe(IV)=O intermediate of a NHFe enzyme, namely the halogenase SyrB2 from the bacterium Pseudomonas syringae pv. syringae. This intermediate reacts via an initial hydrogen-atom abstraction step, performing subsequent halogenation of the native substrate or hydroxylation of non-native substrates. A correlation of the experimental NRVS data to electronic structure calculations indicates that the substrate directs the orientation of the Fe(IV)=O intermediate, presenting specific frontier molecular orbitals that can activate either selective halogenation or hydroxylation.
View details for DOI 10.1038/nature12304
View details for Web of Science ID 000321910700032
View details for PubMedID 23868262
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Elucidation of the Fe(IV)=O intermediate in the catalytic cycle of the halogenase SyrB2.
Nature
2013; 499 (7458): 320-323
Abstract
Mononuclear non-haem iron (NHFe) enzymes catalyse a broad range of oxidative reactions, including halogenation, hydroxylation, ring closure, desaturation and aromatic ring cleavage reactions. They are involved in a number of biological processes, including phenylalanine metabolism, the production of neurotransmitters, the hypoxic response and the biosynthesis of secondary metabolites. The reactive intermediate in the catalytic cycles of these enzymes is a high-spin S = 2 Fe(IV)=O species, which has been trapped for a number of NHFe enzymes, including the halogenase SyrB2 (syringomycin biosynthesis enzyme 2). Computational studies aimed at understanding the reactivity of this Fe(IV)=O intermediate are limited in applicability owing to the paucity of experimental knowledge about its geometric and electronic structure. Synchrotron-based nuclear resonance vibrational spectroscopy (NRVS) is a sensitive and effective method that defines the dependence of the vibrational modes involving Fe on the nature of the Fe(IV)=O active site. Here we present NRVS structural characterization of the reactive Fe(IV)=O intermediate of a NHFe enzyme, namely the halogenase SyrB2 from the bacterium Pseudomonas syringae pv. syringae. This intermediate reacts via an initial hydrogen-atom abstraction step, performing subsequent halogenation of the native substrate or hydroxylation of non-native substrates. A correlation of the experimental NRVS data to electronic structure calculations indicates that the substrate directs the orientation of the Fe(IV)=O intermediate, presenting specific frontier molecular orbitals that can activate either selective halogenation or hydroxylation.
View details for DOI 10.1038/nature12304
View details for PubMedID 23868262
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Nuclear resonance vibrational spectroscopic and computational study of high-valent diiron complexes relevant to enzyme intermediates.
Proceedings of the National Academy of Sciences of the United States of America
2013; 110 (16): 6275-6280
Abstract
High-valent intermediates of binuclear nonheme iron enzymes are structurally unknown despite their importance for understanding enzyme reactivity. Nuclear resonance vibrational spectroscopy combined with density functional theory calculations has been applied to structurally well-characterized high-valent mono- and di-oxo bridged binuclear Fe model complexes. Low-frequency vibrational modes of these high-valent diiron complexes involving Fe motion have been observed and assigned. These are independent of Fe oxidation state and show a strong dependence on spin state. It is important to note that they are sensitive to the nature of the Fe2 core bridges and provide the basis for interpreting parallel nuclear resonance vibrational spectroscopy data on the high-valent oxo intermediates in the binuclear nonheme iron enzymes.
View details for DOI 10.1073/pnas.1304238110
View details for PubMedID 23576760
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Nuclear resonance vibrational spectroscopic and computational study of high-valent diiron complexes relevant to enzyme intermediates
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2013; 110 (16): 6269-6280
Abstract
High-valent intermediates of binuclear nonheme iron enzymes are structurally unknown despite their importance for understanding enzyme reactivity. Nuclear resonance vibrational spectroscopy combined with density functional theory calculations has been applied to structurally well-characterized high-valent mono- and di-oxo bridged binuclear Fe model complexes. Low-frequency vibrational modes of these high-valent diiron complexes involving Fe motion have been observed and assigned. These are independent of Fe oxidation state and show a strong dependence on spin state. It is important to note that they are sensitive to the nature of the Fe2 core bridges and provide the basis for interpreting parallel nuclear resonance vibrational spectroscopy data on the high-valent oxo intermediates in the binuclear nonheme iron enzymes.
View details for DOI 10.1073/pnas.1304238110
View details for Web of Science ID 000318041500021
View details for PubMedCentralID PMC3631696
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Comparison of High-Spin and Low-Spin Nonheme Fe-III-OOH Complexes in O-O Bond Homolysis and H-Atom Abstraction Reactivities
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2013; 135 (8): 3286-3299
Abstract
The geometric and electronic structures and reactivity of an S = 5/2 (HS) mononuclear nonheme (TMC)Fe(III)-OOH complex are studied by spectroscopies, calculations, and kinetics and compared with the results of previous studies of S = 1/2 (LS) Fe(III)-OOH complexes to understand parallels and differences in mechanisms of O-O bond homolysis and electrophilic H-atom abstraction reactions. The homolysis reaction of the HS [(TMC)Fe(III)-OOH](2+) complex is found to involve axial ligand coordination and a crossing to the LS surface for O-O bond homolysis. Both HS and LS Fe(III)-OOH complexes are found to perform direct H-atom abstraction reactions but with very different reaction coordinates. For the LS Fe(III)-OOH, the transition state is late in O-O and early in C-H coordinates. However, for the HS Fe(III)-OOH, the transition state is early in O-O and further along in the C-H coordinate. In addition, there is a significant amount of electron transfer from the substrate to the HS Fe(III)-OOH at transition state, but that does not occur in the LS transition state. Thus, in contrast to the behavior of LS Fe(III)-OOH, the H-atom abstraction reactivity of HS Fe(III)-OOH is found to be highly dependent on both the ionization potential and the C-H bond strength of the substrate. LS Fe(III)-OOH is found to be more effective in H-atom abstraction for strong C-H bonds, while the higher reduction potential of HS Fe(III)-OOH allows it to be active in electrophilic reactions without the requirement of O-O bond cleavage. This is relevant to the Rieske dioxygenases, which are proposed to use a HS Fe(III)-OOH to catalyze cis-dihydroxylation of a wide range of aromatic compounds.
View details for DOI 10.1021/ja400183g
View details for Web of Science ID 000315618900064
View details for PubMedID 23368958
View details for PubMedCentralID PMC3614352
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Nuclear Resonance Vibrational Spectroscopy and DFT study of Peroxo-Bridged Biferric Complexes: Structural Insight into Peroxo Intermediates of Binuclear Non-heme Iron Enzymes
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2013; 52 (4): 1294-1298
View details for DOI 10.1002/anie.201208240
View details for Web of Science ID 000313719300042
View details for PubMedID 23225363
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Mononuclear nickel(II)-superoxo and nickel(III)-peroxo complexes bearing a common macrocyclic TMC ligand
CHEMICAL SCIENCE
2013; 4 (4): 1502-1508
Abstract
Mononuclear metal-dioxygen adducts, such as metal-superoxo and -peroxo species, are generated as key intermediates in the catalytic cycles of dioxygen activation by heme and non-heme metalloenzymes. We have shown recently that the geometric and electronic structure of the Ni-O2 core in [Ni(n-TMC)(O2)]+ (n = 12 and 14) varies depending on the ring size of the supporting TMC ligand. In this study, mononuclear Ni(II)-superoxo and Ni(III)-peroxo complexes bearing a common macrocylic 13-TMC ligand, such as [NiII(13-TMC)(O2)]+ and [NiIII(13-TMC)(O2)]+, were synthesized in the reaction of [NiII(13-TMC)(CH3CN)]2+ and H2O2 in the presence of tetramethylammonium hydroxide (TMAH) and triethylamine (TEA), respectively. The Ni(II)-superoxo and Ni(III)-peroxo complexes bearing the common 13-TMC ligand were successfully characterized by various spectroscopic methods, X-ray crystallography, and DFT calculations. Based on the combined experimental and theoretical studies, we conclude that the superoxo ligand in [NiII(13-TMC)(O2)]+ is bound in an end-on fashion to the nickel(II) center, whereas the peroxo ligand in [NiIII(13-TMC)(O2)]+ is bound in a side-on fashion to the nickel(III) center. Reactivity studies performed with the Ni(II)-superoxo and Ni(III)-peroxo complexes toward organic substrates reveal that the former possesses an electrophilic character, whereas the latter is an active oxidant in nucleophilic reaction.
View details for DOI 10.1039/c3sc22173c
View details for Web of Science ID 000315597900013
View details for PubMedCentralID PMC3646059
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Structure and reactivity of a mononuclear non-haem iron(III)-peroxo complex
NATURE
2011; 478 (7370): 502-505
Abstract
Oxygen-containing mononuclear iron species--iron(III)-peroxo, iron(III)-hydroperoxo and iron(IV)-oxo--are key intermediates in the catalytic activation of dioxygen by iron-containing metalloenzymes. It has been difficult to generate synthetic analogues of these three active iron-oxygen species in identical host complexes, which is necessary to elucidate changes to the structure of the iron centre during catalysis and the factors that control their chemical reactivities with substrates. Here we report the high-resolution crystal structure of a mononuclear non-haem side-on iron(III)-peroxo complex, [Fe(III)(TMC)(OO)](+). We also report a series of chemical reactions in which this iron(III)-peroxo complex is cleanly converted to the iron(III)-hydroperoxo complex, [Fe(III)(TMC)(OOH)](2+), via a short-lived intermediate on protonation. This iron(III)-hydroperoxo complex then cleanly converts to the ferryl complex, [Fe(IV)(TMC)(O)](2+), via homolytic O-O bond cleavage of the iron(III)-hydroperoxo species. All three of these iron species--the three most biologically relevant iron-oxygen intermediates--have been spectroscopically characterized; we note that they have been obtained using a simple macrocyclic ligand. We have performed relative reactivity studies on these three iron species which reveal that the iron(III)-hydroperoxo complex is the most reactive of the three in the deformylation of aldehydes and that it has a similar reactivity to the iron(IV)-oxo complex in C-H bond activation of alkylaromatics. These reactivity results demonstrate that iron(III)-hydroperoxo species are viable oxidants in both nucleophilic and electrophilic reactions by iron-containing enzymes.
View details for DOI 10.1038/nature10535
View details for Web of Science ID 000296194200040
View details for PubMedID 22031443
View details for PubMedCentralID PMC3306242
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Variable-temperature variable-field magnetic circular dichroism (VTVH MCD) and nuclear resonance vibrational spectroscopy (NRVS) studies on Fe-IV=O intermediates: Electronic and geometric structural insight into reactivity
241st National Meeting and Exposition of the American-Chemical-Society (ACS)
AMER CHEMICAL SOC. 2011
View details for Web of Science ID 000291982802611
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S K-Edge X-Ray Absorption Spectroscopy and Density Functional Theory Studies of High and Low Spin {FeNO}(7) Thiolate Complexes: Exchange Stabilization of Electron Delocalization in {FeNO}(7) and {FeO2}(8)
INORGANIC CHEMISTRY
2011; 50 (2): 427-436
Abstract
S K-edge X-ray absorption spectroscopy (XAS) is a direct experimental probe of metal ion electronic structure as the pre-edge energy reflects its oxidation state, and the energy splitting pattern of the pre-edge transitions reflects its spin state. The combination of sulfur K-edge XAS and density functional theory (DFT) calculations indicates that the electronic structures of {FeNO}(7) (S = 3/2) (S(Me2)N(4)(tren)Fe(NO), complex I) and {FeNO}(7) (S = 1/2) ((bme-daco)Fe(NO), complex II) are Fe(III)(S = 5/2)-NO(-)(S = 1) and Fe(III)(S = 3/2)-NO(-)(S = 1), respectively. When an axial ligand is computationally added to complex II, the electronic structure becomes Fe(II)(S = 0)-NO•(S = 1/2). These studies demonstrate how the ligand field of the Fe center defines its spin state and thus changes the electron exchange, an important factor in determining the electron distribution over {FeNO}(7) and {FeO(2)}(8) sites.
View details for DOI 10.1021/ic1006378
View details for Web of Science ID 000285956600011
View details for PubMedCentralID PMC3130116
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Nuclear Resonance Vibrational Spectroscopy on the Fe-IV=O S=2 Non-Heme Site in TMG(3)tren: Experimentally Calibrated Insights into Reactivity
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2011; 50 (14): 3215-3218
View details for DOI 10.1002/anie.201007692
View details for Web of Science ID 000288796600017
View details for PubMedID 21370371
View details for PubMedCentralID PMC3085250
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Definition of the intermediates and mechanism of the anticancer drug bleomycin using nuclear resonance vibrational spectroscopy and related methods
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2010; 107 (52): 22419-22424
Abstract
Bleomycin (BLM) is a glycopeptide anticancer drug capable of effecting single- and double-strand DNA cleavage. The last detectable intermediate prior to DNA cleavage is a low spin Fe(III) peroxy level species, termed activated bleomycin (ABLM). DNA strand scission is initiated through the abstraction of the C-4' hydrogen atom of the deoxyribose sugar unit. Nuclear resonance vibrational spectroscopy (NRVS) aided by extended X-ray absorption fine structure spectroscopy and density functional theory (DFT) calculations are applied to define the natures of Fe(III)BLM and ABLM as (BLM)Fe(III)─OH and (BLM)Fe(III)(η(1)─OOH) species, respectively. The NRVS spectra of Fe(III)BLM and ABLM are strikingly different because in ABLM the δFe─O─O bending mode mixes with, and energetically splits, the doubly degenerate, intense O─Fe─N(ax) transaxial bends. DFT calculations of the reaction of ABLM with DNA, based on the species defined by the NRVS data, show that the direct H-atom abstraction by ABLM is thermodynamically favored over other proposed reaction pathways.
View details for DOI 10.1073/pnas.1016323107
View details for Web of Science ID 000285684200017
View details for PubMedID 21149675
View details for PubMedCentralID PMC3012509
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S K-Edge X-Ray Absorption Spectroscopy and Density Functional Theory Studies of High and Low Spin {FeNO}(7) Thiolate Complexes: Exchange Stabilization of Electron Delocalization in {FeNO}(7) and {FeO(2)}(8).
Inorganic chemistry
2010
Abstract
S K-edge X-ray absorption spectroscopy (XAS) is a direct experimental probe of metal ion electronic structure as the pre-edge energy reflects its oxidation state, and the energy splitting pattern of the pre-edge transitions reflects its spin state. The combination of sulfur K-edge XAS and density functional theory (DFT) calculations indicates that the electronic structures of {FeNO}(7) (S = 3/2) (S(Me2)N(4)(tren)Fe(NO), complex I) and {FeNO}(7) (S = 1/2) ((bme-daco)Fe(NO), complex II) are Fe(III)(S = 5/2)-NO(-)(S = 1) and Fe(III)(S = 3/2)-NO(-)(S = 1), respectively. When an axial ligand is computationally added to complex II, the electronic structure becomes Fe(II)(S = 0)-NO•(S = 1/2). These studies demonstrate how the ligand field of the Fe center defines its spin state and thus changes the electron exchange, an important factor in determining the electron distribution over {FeNO}(7) and {FeO(2)}(8) sites.
View details for DOI 10.1021/ic1006378
View details for PubMedID 21158471
View details for PubMedCentralID PMC3130116
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Spectroscopic and DFT studies of activated bleomycin and its reactivity
AMER CHEMICAL SOC. 2010
View details for Web of Science ID 000208189303311
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Theoretical studies on structures, C-13 NMR chemical shifts, aromaticity, and chemical reactivity of finite-length open-ended armchair single-walled carbon nanotubes
NANOSCALE
2010; 2 (2): 254-261
Abstract
The geometries, chemical shifts, aromaticity, and reactivity of finite-length open-ended armchair single-walled carbon nanotubes (SWCNTs) have been studied within density functional theory. The widely used model of capping hydrogen atoms at the open ends of a SWCNT changes the chemical activity of the SWCNT and destabilizes the frontier molecular orbitals. The edge pi-orbital of the open ends enhances both pi- and sigma-aromaticity of the first belt of hexagons of carbon atoms at the open ends. The effect of the open ends on the structure and chemical reactivity of the SWCNT reaches only the first several layers of the hexagons of carbon atoms. Additions of carbene and dichlorocarbene to the nanotube reveal that the open ends have higher reactivities than the inner regions.
View details for DOI 10.1039/b9nr00159j
View details for Web of Science ID 000275577100010
View details for PubMedID 20644802
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Peroxo and oxo intermediates in mononuclear nonheme iron enzymes and related active sites
CURRENT OPINION IN CHEMICAL BIOLOGY
2009; 13 (1): 99-113
Abstract
Fe(III)OOH and Fe(IV)O intermediates have now been documented in a number of nonheme iron active sites. In this Current Opinion we use spectroscopy combined with electronic structure calculations to define the frontier molecular orbitals (FMOs) of these species and their contributions to reactivity. For the low-spin Fe(III)OOH species in activated bleomycin we show that the reactivity of this nonheme iron intermediate is very different from that of the analogous Compound 0 of cytochrome P450. For Fe(IV)O S=1 model species we experimentally define the electronic structure and its contribution to reactivity, and computationally evaluate how this would change for the Fe(IV)O S=2 intermediates found in nonheme iron enzymes.
View details for DOI 10.1016/j.cbpa.2009.02.011
View details for Web of Science ID 000266192400013
View details for PubMedID 19278895
View details for PubMedCentralID PMC2676221
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Further insights into the mechanism of the reaction of activated bleomycin with DNA
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2008; 105 (36): 13241-13245
Abstract
Bleomycin (BLM) is a glycopeptide anticancer drug that effectively carries out single- and double-stranded DNA cleavage. Activated BLM (ABLM), a low-spin ferric-hydroperoxide, BLM-Fe(III)-OOH, is the last intermediate detected before DNA cleavage. We have previously shown through experiments and DFT calculations that both ABLM decay and reaction with H atom donors proceed via direct H atom abstraction. However, the rate of ABLM decay had been previously found, based on indirect methods, to be independent of the presence of DNA. In this study, we use a circular dichroism (CD) feature unique to ABLM to directly monitor the kinetics of ABLM reaction with a DNA oligonucleotide. Our results show that the ABLM + DNA reaction is appreciably faster, has a different kinetic isotope effect, and has a lower Arrhenius activation energy than does ABLM decay. In the ABLM reaction with DNA, the small normal k(H)/k(D) ratio is attributed to a secondary solvent effect through DFT vibrational analysis of reactant and transition state (TS) frequencies, and the lower E(a) is attributed to the weaker bond involved in the abstraction reaction (C-H for DNA and N-H for the decay in the absence of DNA). The DNA dependence of the ABLM reaction indicates that DNA is involved in the TS for ABLM decay and thus reacts directly with BLM-Fe(III)-OOH instead of its decay product.
View details for DOI 10.1073/pnas.0806378105
View details for Web of Science ID 000259251700014
View details for PubMedID 18757754
View details for PubMedCentralID PMC2533175
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Ozonization at the vacancy defect site of the single-walled carbon nanotube
JOURNAL OF PHYSICAL CHEMISTRY B
2006; 110 (26): 13037-13044
Abstract
The ozonization at the vacancy defect site of the single-walled carbon nanotube has been studied by static quantum mechanics and atom-centered density matrix propagation based ab initio molecular dynamics within a two-layered ONIOM approach. Among five different reaction pathways at the vacancy defect, the reaction involving the unsaturated active carbon atom is the most probable pathway, where ozone undergoes fast dissociation at the active carbon atom at 300 K. Complementary to the experiments, our work provides a microscopic understanding of the ozonization at the vacancy defect site of the single-walled carbon nanotube.
View details for DOI 10.1021/jp055999x
View details for Web of Science ID 000238645700035
View details for PubMedID 16805611
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Chemical reaction of nitric oxides with the 5-1DB defect of the single-walled carbon nanotube
JOURNAL OF PHYSICAL CHEMISTRY B
2006; 110 (5): 1999-2005
Abstract
In this work, we applied a two-layered ONIOM (B3LYP/6-31G(d):UFF) method to study the reaction of nitric oxides with a 5-1DB defect on the sidewall of the single-walled carbon nanotube (SWCNT). We have chosen a suitable ONIOM model for the calculation of the SWCNT based on the analyses of the frontier molecular orbitals, local density of states, and natural bond orbitals. Our calculations clearly indicate that the 5-1DB defect is the chemically active center of the SWCNT. In the reaction of nitric oxides with the defected SWCNT, the 5-1DB defect site can capture a nitrogen atom from nitric oxides, yielding the N-substitutionally doped SWCNT. We have explored the reaction pathway in detail. Our work verifies the chemical reactivity of the 5-1DB defects of the SWCNTs, indicates that the 5-1DB defect is a possible site for the functionalization of the SWCNTs, and demonstrates a possible way to fabricate position controllable substitutionally doped SWCNTs with a low doping concentration under mild conditions via some simple chemical reactions.
View details for DOI 10.1021/jp053931b
View details for Web of Science ID 000235284300009
View details for PubMedID 16471775
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Electronic properties and reactivity of Pt-doped carbon nanotubes
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
2006; 8 (30): 3528-3539
Abstract
The structures of the (5,5) single-walled carbon nanotube (SWCNT) segments with hemispheric carbon cages capped at the ends (SWCNT rod) and the Pt-doped SWCNT rods have been studied within density functional theory. Our theoretical studies find that the hemispheric cages introduce localized states on the caps. The cap-Pt-doped SWCNT rods can be utilized as sensors because of the sensitivity of the doped Pt atom. The Pt-doped SWCNT rods can also be used as catalysts, where the doped Pt atom serves as the enhanced and localized active center on the SWCNT. The adsorptions of C(2)H(4) and H(2) on the Pt atom in the Pt-doped SWCNT rods reveal different adsorption characteristics. The adsorption of C(2)H(4) on the Pt atom in all of the three Pt-doped SWCNT rods studied (cap-end-doped, cap-doped, and wall-doped) is physisorption with the strongest interaction occurring in the middle of the sidewall of the SWCNT. On the other hand, the adsorption of H(2) on the Pt atom at the sidewall of the SWCNT is chemisorption resulting in the decomposition of H(2), and the adsorption of H(2) at the hemispheric caps is physisorption.
View details for DOI 10.1039/b604032m
View details for Web of Science ID 000239313600007
View details for PubMedID 16871342