We develop ultrafast vibrational spectroscopies to study the molecular dynamics of aqueous solutions and biophysical processes.
Research Interests:
The Tokmakoff group studies the molecular dynamics of water, aqueous solutions, and bimolecular binding processes involving proteins and DNA.
Despite its outsized role in our lives, numerous aspects of water chemistry are poorly understood at a molecular level, largely because of the lack of insightful experimental tools. Water’s properties emerge from a complex interplay of interactions at a molecular level, including hydrogen bonding, electrostatics, and repulsion. We study water’s hydrogen-bonding network, which fluctuates and rearranges on femtosecond-to-picosecond timescales, and its dynamic interactions with solutes varying from ions to small molecules to proteins. These studies are aimed at understanding a variety of phenomena, including the structure of protons in water, the transport of ions in electrolyte solutions, the properties of electrolytes at solid interfaces, and the role of water in bimolecular reactions.
Our group also investigates how proteins and DNA spontaneously self-assemble into well-defined structures, including protein–protein interactions and DNA hybridization. In these processes, two binding partners diffusively encounter one another, and while interacting nonspecifically, they recognize and bind each other with site-specific contacts. Our studies focus on the specific details of how molecules interact during their initial encounter.
In seeking solutions to all these scientific problems, our experimental approach is to develop and use structure-sensitive ultrafast vibrational spectroscopy as a tool for following the time evolution of molecular structure. One important technique is two-dimensional infrared spectroscopy, which we use to capture information on transient molecular structure and dynamics from femtosecond to kilosecond time scales. We are also developing single molecule vibrational spectroscopy to study stochastic bimolecular processes in solution.
More details on all these topics are available on the Tokmakoff Group Website.
Representative Publications
Tokmakoff Group Publications on Google Scholar
1. “Fluorescence-Encoded Infrared Vibrational Spectroscopy with Single-Molecule Sensitivity,” Lukas Whaley-Mayda, Abhirup Guha, Samuel Penwell, and Andrei Tokmakoff, Journal of the American Chemical Society, 143 (2021) 3060–3064. https://dx.doi.org/10.1021/jacs.1c00542
2. “Crossover from Hydrogen to Chemical Bonding,” Bogdan Dereka, Qi Yu, Nicholas H. C. Lewis, William B. Carpenter, Joel M. Bowman, Andrei Tokmakoff, Science, 371 (2021) 160-164. DOI: 10.1126/science.abe1951
3. “Structural characterization of protonated water clusters confined in HZSM-5 zeolites,” John H. Hack†, James P. Dombrowski†, Xinyou Ma†, Yaxin Chen, Nicholas H. C. Lewis, William B. Carpenter, Chenghan Li, Gregory A. Voth, Harold H. Kung and Andrei Tokmakoff, Journal of the American Chemical Society, 143 (2021) 10203–10213. https://doi.org/10.1021/jacs.1c03205
4. “Computational IR Spectroscopy of Insulin Dimer Structure and Conformational Heterogeneity,” Chi-Jui Feng, Anton Sinitskiy, Vijay Pande, and Andrei Tokmakoff, Journal of Physical Chemistry B, 125 (2021) 4620–4633. https://doi.org/10.1021/acs.jpcb.1c00399
5. “Temperature-Jump 2D IR Spectroscopy with Intensity-Modulated CW Optical Heating,” Brennan Ashwood, Nicholas H. C. Lewis, Paul J. Sanstead, Andrei Tokmakoff, Journal of Physical Chemistry B, 124 (2020) 8665–8677. https://doi.org/10.1021/acs.jpcb.0c07177
6. “Vibrational Probe of Aqueous Electrolytes—The Field is Not Enough,” Nicholas H. C. Lewis, Aysenur Iscen, Alanna Felts, Bogdan Dereka, George C. Schatz, and Andrei Tokmakoff, Journal of Physical Chemistry B, 124 (2020) 7013–7026. https://doi.org/10.1021/acs.jpcb.0c05510
7. “Revealing the Dynamical Role of Co-solvents in the Coupled Folding and Dimerization of Insulin,” Xin-Xing Zhang and Andrei Tokmakoff, Journal of Physical Chemistry Letters, 11 (2020) 4353–4358. https://doi.org/10.1021/acs.jpclett.0c00982
8. “Insulin dissociates by diverse mechanisms of coupled unfolding and unbinding,” Adam Antoszewski, Chi-Jui Feng, Bodhi Vani, Erik Thiede, Lu Hong, Jonathan Weare, Andrei Tokmakoff, and Aaron Dinner, Journal of Physical Chemistry B, 124 (2020) 5571–5587. https://doi.org/10.1021/acs.jpcb.0c03521
9. “Oxidized Derivatives of 5-Methylcytosine Alter the Stability and Dehybridization Dynamics of Duplex DNA,” Paul Sanstead, Brennan Ashwood, Qing Dai, Chuan He, Andrei Tokmakoff, Journal of Physical Chemistry B, 124 (2020) 1160-1174. https://doi.org/10.1021/acs.jpcb.9b11511
10. “Entropic Barriers in the Kinetics of Aqueous Proton Transfer,” William B. Carpenter, Nicholas H.C. Lewis, Joseph A. Fournier, and Andrei Tokmakoff, Journal of Chemical Physics, 151 (2019) 034501-1-11. https://doi.org/10.1063/1.5108907
11. “Broadband 2D IR spectroscopy reveals dominant asymmetric H5O2+ proton hydration structures in acid solutions,” Joseph A. Fournier, William B. Carpenter, Nicholas H.C. Lewis, and Andrei Tokmakoff, Nature Chemistry, 10 (2018) 932-937. DOI: 10.1038/s41557-018-0091-y