Professor of Chemistry
Professor Hammes-Schiffer received her B.A. degree in Chemistry from Princeton University in 1988 and her Ph.D. in Chemistry from Stanford University in 1993. After working as a postdoctoral fellow at AT&T Bell Laboratories, she was a faculty member at the University of Notre Dame from 1995-2000 and at The Pennsylvania State University from 2000-2012. In August 2012, Professor Hammes-Schiffer joined the faculty of the Department of Chemistry at the University of Illinois. She is also the Editor-in-Chief of Chemical Reviews.
Our research centers on the development and application of theoretical and computational methods for describing chemical reactions in condensed phases and at interfaces. The group is divided into three general areas: proton-coupled electron transfer reactions, enzymatic processes, and non-Born-Oppenheimer electronic structure methods. Our overall objective is to elucidate the fundamental physical principles underlying charge transfer reactions. Our theories also assist in the interpretation of experimental data and provide experimentally testable predictions.
Proton-coupled electron transfer
Proton-coupled electron transfer (PCET) reactions play a critical role in a wide range of chemical and biological processes. We have developed a general theoretical formulation for PCET and have applied this theory to experimentally studied reactions in solution, proteins, and electrochemistry. This theory treats the electrons and transferring proton(s) quantum mechanically and includes the solvent and solute reorganization as well as the proton donor-acceptor motion. We have derived a series of analytical expressions for the rate constants of PCET reactions and for the current densities of electrochemical PCET processes. We have also developed methodology to simulate the nonadiabatic ultrafast dynamics of photoinduced PCET reactions. Applications of this theory have provided explanations for the experimental trends in the rates and deuterium kinetic isotope effects, and in some cases the temperature and pH dependences. Current applications focus on the design of molecular electrocatalysts and photocatalysts for hydrogen oxidation and production in energy conversion devices such as solar cells.
We have developed a hybrid quantum/classical molecular dynamics approach for simulating proton and hydride transfer reactions in enzymes. This hybrid approach includes electronic and nuclear quantum effects, as well as the motion of the entire solvated enzyme. The methodology provides detailed mechanistic information at the molecular level and allows the calculation of rate constants and kinetic isotope effects. Applications of this methodology have led to the concept of a network of coupled equilibrium motions extending throughout the enzyme and representing conformational changes that facilitate the chemical reaction. Mutations distal to the active site can significantly impact the catalytic rate constant by altering the conformational motions of the entire enzyme and thereby changing the probability of sampling conformations conducive to the catalyzed reaction. Currently we are developing methods for calculating the vibrational Stark effect in enzymes to further probe the roles of hydrogen bonding, electrostatics, and conformational motions in enzyme catalysis. We are also extending our studies to ribozymes (RNA enzymes) as well as protein enzymes.
Non-Born-Oppenheimer electronic structure methods
We have developed the nuclear-electronic orbital (NEO) method for the incorporation of nuclear quantum effects into electronic structure calculations. In the NEO approach, specified nuclei are treated quantum mechanically on the same level as the electrons, and mixed nuclear-electronic wavefunctions are calculated variationally with molecular orbital methods. Correlation among electrons and nuclei can be included with multiconfigurational methods, perturbation theory, or density functional theory. For hydrogen transfer and hydrogen bonding systems, typically the key hydrogen nuclei and all electrons are treated quantum mechanically. The advantages of the NEO approach are that the Born-Oppenheimer separation between electrons and specified protons is avoided, nonadiabatic effects are inherently included, and excited electron-proton vibronic states may be calculated. Current efforts are directed toward including electron-proton correlation with explicitly correlated wavefunction methods and multicomponent density functional theory.
- P. Thaplyal, A. Ganguly, S. Hammes-Schiffer, and P. C. Bevilacqua, "Inverse thio effects in the hepatitis delta virus ribozyme reveal that the reaction pathway is controlled by metal ion charge density," Biochemistry 54, 2160-2175 (2015).
- P. Hanoian, C. T. Liu, S. Hammes-Schiffer, and S. J. Benkovic, "Perspectives on electrostatics and conformational motions in enzyme catalysis," Acc. Chem. Res. 48, 482-489 (2015).
- P. Goyal, C. A. Schwerdtfeger, A. V. Soudackov, and S. Hammes-Schiffer, "Nonadiabatic dynamics of photoinduced proton-coupled electron transfer in a solvated phenol-amine complex," J. Phys. Chem. B 119, 2758-2768 (2015) .
- S. Zhang, A. Ganguly, P. Goyal, J. Bingamin, P. C. Bevilacqua, and S. Hammes-Schiffer, "Role of the active site guanine in the glmS ribozyme self-cleavage mechanism: Quantum mechanical/molecular mechanical free energy simulations," J. Am. Chem. Soc. 137, 784-798 (2015).
- S. Ghosh and S. Hammes-Schiffer, "Calculation of electrochemical reorganization energies for redox molecules at self-assembled monolayer modified electrodes," J. Phys. Chem. Lett. 6, 1-5 (2015).
- B. H. Solis, A. G. Maher, T. Honda, D. C. Powers, D. G. Nocera, and S. Hammes-Schiffer, "Theoretical analysis of cobalt hangman prophyrins: Ligand dearomatization and mechanistic implications for hydrogen evolution," ACS Catal. 4, 4516–4526 (2014).
- C. T. Liu, K. Francis, J. Layfield, X. Huang, S. Hammes-Schiffer, A. Kohen, and S. J. Benkovic, "Escherichia coli dihydrofolate reductase catalyzed proton and hydride transfers: Temporal order and the roles of Asp27 and Tyr100," Proc. Nat. Acad. Sci. USA 111, 18231-18236 (2014).
- N. M. Tubman, I. Kylänpää, S. Hammes-Schiffer, and D. M. Ceperley, "Beyond the Born-Oppenheimer approximation with quantum Monte Carlo," Phys. Rev. A 90, 042507 (2014).
- D. K. Bediako, B. H. Solis, D. K. Dogutan, M. M. Roubelakis, A. G. Maher, C. H. Lee, M. B. Chambers, S. Hammes-Schiffer, and D. G. Nocera, "Role of pendant proton relays and proton-coupled electron transfer on the hydrogen evolution reaction by nickel hangman porphyrins," Proc. Natl. Acad. Sci. USA 111, 15001-15006 (2014).
- A. V. Soudackov and S. Hammes-Schiffer, "Probing nonadiabaticity in the proton-coupled electron transfer reaction catalyzed by soybean lipoxygenase," J. Phys. Chem. Lett. 5, 3274-3278 (2014).
- M. T. Huynh, W. Wang, T. B. Rauchfuss, and S. Hammes-Schiffer, "Computational investigation of [FeFe]-hydrogenase models: Characterization of singly and doubly protonated intermediates and mechanistic insights," Inorg. Chem. 53, 10301-10311 (2014).
- M. T. Huynh, D. Schilter, S. Hammes-Schiffer, and T. B. Rauchfuss, "Protonation of nickel-iron hydrogenase models proceeds after isomerization at nickel," J. Am. Chem. Soc. 136, 12385-12395 (2014).
- C. T. Liu, J. P. Layfield, R. J. Stewart III, J. B. French, P. Hanoian, J. B. Asbury, S. Hammes-Schiffer, and S. J. Benkovic, "Probing the electrostatics of active site microenvironments along the catalytic cycle for Escherichia coli dihydrofolate reductase," J. Am. Chem. Soc. 136, 10349-10360 (2014).
- S. Hu, S. C. Sharma, A. D. Scouras, A. V. Soudackov, C. A. Marcus Carr, S. Hammes-Schiffer, T. Alber, and J.P. Klinman, "Extremely elevated room-temperature kinetic isotope effects quantify the critical role of barrier width in enzymatic C-H activation," J. Am. Chem. Soc. 136, 8157-8160 (2014).
- B. H. Solis and S. Hammes-Schiffer, "Proton-coupled electron transfer in molecular electrocatalysis: Theoretical methods and design principles," Inorg. Chem. 53, 6427-6443 (2014).
- S. Ghosh, S. Horvath, A. V. Soudackov, and S. Hammes-Schiffer, "Electrochemical solvent reorganization energies in the framework of the polarizable continuum model," J. Chem. Theory Comput. 10, 2091-2102 (2014).
- J. P. Schwans, P. Hanoian, B. J. Lengerich, F. Sunden, A. Gonzalez, Y. Tsai, S. Hammes-Schiffer, and D. Herschlag, "Experimental and computational mutagenesis to investigate the positioning of a general base within an enzyme active site," Biochemistry 53, 2541-2555 (2014).
- C. A. Schwerdtfeger, A. V. Soudackov, and S. Hammes-Schiffer, "Nonadiabatic dynamics of electron transfer in solution: Explicit and implicit solvent treatments that include multiple relaxation time scales," J. Chem. Phys. 140, 034113 (2014).
- A. Ganguly, P. Thaplyal, E. Rosta, P. C. Bevilacqua, and S. Hammes-Schiffer, "Quantum mechanical/molecular mechanical free energy simulations of the self-cleavage reaction in the hepatitis delta virus ribozyme," J. Am. Chem. Soc. 136, 1483-1496 (2014).
- S. Chakraborty, J. Reed, M. Ross, M. J. Nilges, I. D. Petrik, S. Ghosh, S. Hammes-Schiffer, J. T. Sage, Y. Zhang, C. E. Schulz, and Y. Lu, "Spectroscopic nd computational study of a nonheme iron nitrosyl center in a biosynthetic model of nitric oxide reductase," Angew. Chem. Int. Ed. 53, 2417-2421 (2014).
- J. P. Layfield and S. Hammes-Schiffer, "Hydrogen tunneling in enzymes and biomimetic models," Chem. Rev. 114, 3466-3494 (2014).
- Fellow, Biophysical Society, 2015
- Member, International Academy of Quantum Molecular Science, 2014
- Member, U.S. National Academy of Sciences, 2013
- Fellow, American Association for the Advancement of Science, 2013
- Member of American Academy of Arts and Sciences, 2012
- Fellow of the American Chemical Society, 2011
- NIH MERIT Award, 2011
- Fellow of the American Physical Society, 2010
- American Chemical Society Akron Section Award, 2008
- Iota Sigma Pi Agnes Fay Morgan Research Award, 2005
- International Academy of Quantum Molecular Science Medal, 2005
- Alexander M. Cruickshank Lecturer, Gordon Research Conferences, 2004
- NSF Creativity Extension Award, 2003
- Camille Dreyfus Teacher-Scholar Award, 1999
- Alfred P. Sloan Research Fellowship, 1998
- Ralph E. Powe Junior Faculty Enhancement Award, Oak Ridge Associated Universities, 1998
- NSF CAREER Award, 1996