Sharon Hammes-Schiffer

The application of her work in PCET has elucidated the nature of various chemical mechanisms and led to her temperature dependence model of PCET rates.[13][14] One such process, Quinol Oxidation, studied the Kinetic isotope effect on Ubiquinol and Plastoquinol with regards to temperature, finding that the free energy of activation is greater for hydrogen than for deuterium, meaning the reaction is slower for hydrogen and therefore irreversible, if specific conditions are satisfied.[15] This finding has since been used by other investigators to reinforce the notion that reactions may or may not be unidirectional by influencing reaction rates with the kinetic isotope effect.[16] Additionally, her study of PCET in Iron Bi-imidazoline complexes has refined common comprehension of PCET, having proven her theory that electron transfer rate increases under the kinetic isotope effect as "the proton transfer distance increases and the electron transfer distance decreases."[17] These mechanisms have helped support the research of other PCET studies, with her main PCET paper, "Theoretical Studies of Proton-Coupled Electron Transfer Reactions",[13] having been cited over 90 times by papers ranging from studying protein motion to enzyme dynamics.[18]

Hammes-Schiffer studies the effects of quantum tunnelling and hydrogen bonding on enzymatic reactions. Her work on Soybean Lipoxygenase-1 changed common perception of a previously proposed tunneling region diagram,[19] finding that the temperature dependence of KIEs are inversely proportional to each other and that active environmental dynamics leads to less of the KIE and promotes catalysis.[20] This finding should be applicable to any other enzymes which can transfer a proton due to the fact that there aren't as many enzymatic options for non-ionic transfer of a proton and therefore tunneling must be used throughout the process.[20]

Hammes-Schiffer has also pioneered work in what she calls the Nuclear-electronic orbital method (NEO) which allows for a more accurate estimate of nuclear properties such as density, geometry, frequencies, electronic coupling, and nuclear motions.[21] As described in her paper, "Incorporation of Nuclear Quantum effects in electronic structure," Radial basis function kernel, a gaussian algorithm used to support vector machines, is applied to determine electronic and molecular orbitals. The NEO approach is specifically applicable in determining the exact mechanisms of hydrogen transfer reactions while accounting for other variables such as quantum tunneling and zero point energy. Hammes-Schiffer claims that the NEO approach is significantly advantageous over other methods that incorporate nuclear quantum effects because of the method's ability to calculate vibrational states, its avoidance of Born–Oppenheimer approximation and its apparent and inherent incorporation of quantum effects.[22]

In her study, published in September 2016, Hammes-Schiffer contributed towards discovering the effects of the active site of the magnesium ion in the Scissile Phosphate cofactor complex. She discovered that rather than the magnesium ion lying in the center of the complex, the ion lies in a separate site, termed the Hoogsteen Face, where it lowers the pKa of the complex in order to facilitate a deprotonation reaction necessary for a self-cleavage reaction.[23]