Stanford Advisors

All Publications

  • Long Vibrational Lifetime R-Selenocyanate Probes for Ultrafast Infrared Spectroscopy: Properties and Synthesis. The journal of physical chemistry. B Fica-Contreras, S. M., Daniels, R., Yassin, O., Hoffman, D. J., Pan, J., Sotzing, G., Fayer, M. D. 2021


    Ultrafast infrared vibrational spectroscopy is widely used for the investigation of dynamics in systems from water to model membranes. Because the experimental observation window is limited to a few times the probe's vibrational lifetime, a frequent obstacle for the measurement of a broad time range is short molecular vibrational lifetimes (typically a few to tens of picoseconds). Five new long-lifetime aromatic selenocyanate vibrational probes have been synthesized and their vibrational properties characterized. These probes are compared to commercial phenyl selenocyanate. The vibrational lifetimes range between 400 and 500 ps in complex solvents, which are some of the longest room-temperature vibrational lifetimes reported to date. In contrast to vibrations that are long-lived in simple solvents such as CCl4, but become much shorter in complex solvents, the probes discussed here have 400 ps lifetimes in complex solvents and even longer in simple solvents. One of them has a remarkable lifetime of 1235 ps in CCl4. These probes have a range of molecular sizes and geometries that can make them useful for placement into different complex materials due to steric reasons, and some of them have functionalities that enable their synthetic incorporation into larger molecules, such as industrial polymers. We investigated the effect of a range of electron-donating and electron-withdrawing para-substituents on the vibrational properties of the CN stretch. The probes have a solvent-independent linear relationship to the Hammett substituent parameter when evaluated with respect to the CN vibrational frequency and the ipso 13C NMR chemical shift.

    View details for DOI 10.1021/acs.jpcb.1c04939

    View details for PubMedID 34339200

  • Distinguishing steric and electrostatic molecular probe orientational ordering via their effects on reorientation-induced spectral diffusion. The Journal of chemical physics Hoffman, D. J., Fica-Contreras, S. M., Pan, J., Fayer, M. D. 2021; 154 (24): 244104


    The theoretical framework for reorientation-induced spectral diffusion (RISD) describes the polarization dependence of spectral diffusion dynamics as measured with two-dimensional (2D) correlation spectroscopy and related techniques. Generally, RISD relates to the orientational dynamics of the molecular chromophore relative to local electric fields of the medium. The predictions of RISD have been shown to be very sensitive to both restricted orientational dynamics (generally arising from steric hindrance) and the distribution of local electric fields relative to the probe (electrostatic ordering). Here, a theory that combines the two effects is developed analytically and supported with numerical calculations. The combined effects can smoothly vary the polarization dependence of spectral diffusion from the purely steric case (least polarization dependence) to the purely electrostatic case (greatest polarization dependence). Analytic approximations of the modified RISD equations were also developed using the orientational dynamics of the molecular probe and two order parameters describing the degree of electrostatic ordering. It was found that frequency-dependent orientational dynamics are a possible consequence of the combined electrostatic and steric effects, providing a test for the applicability of this model to experimental systems. The modified RISD equations were then used to successfully describe the anomalous polarization-dependent spectral diffusion seen in 2D infrared spectroscopy in a polystyrene oligomer system that exhibits frequency-dependent orientational dynamics. The degree of polarization-dependent spectral diffusion enables the extent of electrostatic ordering in a chemical system to be quantified and distinguished from steric ordering.

    View details for DOI 10.1063/5.0053308

    View details for PubMedID 34241361

  • Free Volume Element Sizes and Dynamics in Polystyrene and Poly(methyl methacrylate) Measured with Ultrafast Infrared Spectroscopy. Journal of the American Chemical Society Fica-Contreras, S. M., Hoffman, D. J., Pan, J., Liang, C., Fayer, M. D. 2021


    The size, size distribution, dynamics, and electrostatic properties of free volume elements (FVEs) in polystyrene (PS) and poly(methyl methacrylate) (PMMA) were investigated using the Restricted Orientation Anisotropy Method (ROAM), an ultrafast infrared spectroscopic technique. The restricted orientational dynamics of a vibrational probe embedded in the polymer matrix provides detailed information on FVE sizes and their probability distribution. The probe's orientational dynamics vary as a function of its frequency within the inhomogeneously broadened vibrational absorption spectrum. By characterizing the degree of orientational restriction at different probe frequencies, FVE radii and their probability distribution were determined. PS has larger FVEs and a broader FVE size distribution than PMMA. The average FVE radii in PS and PMMA are 3.4 and 3.0 A, respectively. The FVE radius probability distribution shows that the PS distribution is non-Gaussian, with a tail to larger radii, whereas in PMMA, the distribution is closer to Gaussian. FVE structural dynamics, previously unavailable through other techniques, occur on a 150 ps time scale in both polymers. The dynamics involve FVE shape fluctuations which, on average, conserve the FVE size. FVE radii were associated with corresponding electric field strengths through the first-order vibrational Stark effect of the CN stretch of the vibrational probe, phenyl selenocyanate (PhSeCN). PMMA displayed unique measured FVE radii for each electric field strength. By contrast, PS showed that, while larger radii correspond to unique and relatively weak electric fields, the smallest measured radii map onto a broad distribution of strong electric fields.

    View details for DOI 10.1021/jacs.0c13397

    View details for PubMedID 33630576

  • Pulse-shaped chopping: Eliminating and characterizing heat effects in ultrafast infrared spectroscopy. The Journal of chemical physics Hoffman, D. J., Fica-Contreras, S. M., Pan, J., Fayer, M. D. 2020; 153 (20): 204201


    The infrared pulses used to generate nonlinear signals from a vibrational probe can cause heating via solvent absorption. Solvent absorption followed by rapid vibrational relaxation produces unwanted heat signals by creating spectral shifts of the solvent and probe absorptions. The signals are often isolated by "chopping," i.e., alternately blocking one of the incident pulses. This method is standard in pump-probe transient absorption experiments. As less heat is deposited into the sample when an incident pulse is blocked, the heat-induced spectral shifts give rise to artificial signals. Here, we demonstrate a new method that eliminates heat induced signals using pulse shaping to control pulse spectra. This method is useful if the absorption spectrum of the vibrational probe is narrow compared to the laser bandwidth. By using a pulse shaper to selectively eliminate only frequencies of light resonant with the probe absorption during the "off" shot, part of the pulse energy, and the resulting heat, is delivered to the solvent without generating the nonlinear signal. This partial heating reduces the difference heat signal between the on and off shots. The remaining solvent heat signal can be eliminated by reducing the wings of the on shot spectrum while still resonantly exciting the probe; the heat deposition from the on shot can be matched with that from the off shot, eliminating the solvent heat contribution to the signal. Modification of the pulse sequence makes it possible to measure only the heat signal, permitting the kinetics of heating to be studied.

    View details for DOI 10.1063/5.0031581

    View details for PubMedID 33261482

  • NMR Structural Analysis of Isolated Shaker Voltage-Sensing Domain in LPPG Micelles BIOPHYSICAL JOURNAL Chen, H., Pan, J., Gandhi, D. M., Dockendorff, C., Cui, Q., Chanda, B., Henzler-Wildman, K. A. 2019; 117 (2): 388–98


    The voltage-sensing domain (VSD) is a conserved structural module that regulates the gating of voltage-dependent ion channels in response to a change in membrane potential. Although the structures of many VSD-containing ion channels are now available, our understanding of the structural dynamics associated with gating transitions remains limited. To probe dynamics with site-specific resolution, we utilized NMR spectroscopy to characterize the VSD derived from Shaker potassium channel in 1-palmitoyl-2-hydroxy-sn-glycero-3-phospho-(1'-rac-glycerol) (LPPG) micelles. The backbone dihedral angles predicted based on secondary chemical shifts using torsion angle likeliness obtained from shift (TALOS+) showed that the Shaker-VSD shares many structural features with the homologous Kv1.2/2.1 chimera, including a transition from α-helix to 310 helix in the C-terminal portion of the fourth transmembrane helix. Nevertheless, there are clear differences between the Shaker-VSD and Kv1.2/2.1 chimera in the S2-S3 linker and S3 transmembrane region, where the organization of secondary structure elements in Shaker-VSD appears to more closely resemble the KvAP-VSD. Comparison of microsecond-long molecular dynamics simulations of Kv 1.2-VSD in LPPG micelles and a 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) bilayer showed that LPPG micelles do not induce significant structural distortion in the isolated voltage sensor. To assess the integrity of the tertiary fold, we directly probed the binding of BrMT analog 2-[2-({[3-(2-amino-ethyl)-6-bromo-1H-indol-2-yl]methoxy}k7methyl)-6-bromo-1H-indol-3-yl]ethan-1-amine (BrET), a gating modifier toxin, and identified the location of the putative binding site. Our results suggest that the Shaker-VSD in LPPG micelles is in a native-like fold and is likely to provide valuable insights into the dynamics of voltage-gating and its regulation.

    View details for DOI 10.1016/j.bpj.2019.06.020

    View details for Web of Science ID 000476709900019

    View details for PubMedID 31301804

  • Specificity landscapes unmask submaximal binding site preferences of transcription factors PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Bhimsaria, D., Rodriguez-Martinez, J. A., Pan, J., Roston, D., Korkmaz, E., Cui, Q., Ramanathan, P., Ansari, A. Z. 2018; 115 (45): E10586–E10595


    We have developed Differential Specificity and Energy Landscape (DiSEL) analysis to comprehensively compare DNA-protein interactomes (DPIs) obtained by high-throughput experimental platforms and cutting edge computational methods. While high-affinity DNA binding sites are identified by most methods, DiSEL uncovered nuanced sequence preferences displayed by homologous transcription factors. Pairwise analysis of 726 DPIs uncovered homolog-specific differences at moderate- to low-affinity binding sites (submaximal sites). DiSEL analysis of variants of 41 transcription factors revealed that many disease-causing mutations result in allele-specific changes in binding site preferences. We focused on a set of highly homologous factors that have different biological roles but "read" DNA using identical amino acid side chains. Rather than direct readout, our results indicate that DNA noncontacting side chains allosterically contribute to sculpt distinct sequence preferences among closely related members of transcription factor families.

    View details for DOI 10.1073/pnas.1811431115

    View details for Web of Science ID 000449459000011

    View details for PubMedID 30341220

    View details for PubMedCentralID PMC6233140