About

Sharon Hammes-Schiffer is the A. Barton Hepburn Professor of Chemistry at Princeton University. Her research centers on the development and application of theoretical and computational methods to understand the fundamental physical principles underlying chemical processes. One of her main interests is proton-coupled electron transfer (PCET) reactions, which involve the coupled motions of electrons and protons and are critical in chemistry and biology. Her group has developed a general theoretical formulation for PCET, treating electrons and transferring protons quantum mechanically, including electron and hydrogen tunneling, and incorporating the motions of the proton donor-acceptor mode and the environment. This theory enables the calculation of rate constants and kinetic isotope effects for comparison to experimental data. In addition to PCET theories, her group works on developing methods to include nuclear quantum effects such as zero-point energy and hydrogen tunneling in quantum chemistry calculations and molecular dynamics simulations. She originally developed the nuclear-electronic orbital (NEO) method, which treats specified nuclei quantum mechanically on the same level as electrons, allowing real-time nuclear-electronic quantum dynamical simulations of processes like photoinduced proton transfer, PCET, molecular polaritons, and plasmon-induced reactions. Her research involves a diverse range of applications, including molecular electrocatalysts, proton wires, artificial photosynthetic systems, nanoparticles, electrochemical systems, enzymes, and photoreceptor proteins. Her work has elucidated the roles of hydrogen tunneling, electrostatics, reorganization, and conformational motions in these systems.

Selected publications

• Capturing nuclear quantum effects in high-pressure superconducting hydrides and ice with nuclear-electronic orbital theory

  Zenodo (CERN European Organization for Nuclear Research) · 2026-04-16

  datasetOpen accessSenior author

  This repository contains the needed input, output files, and associated data needed to reproduce the results from the paper, "Capturing nuclear quantum effects in high-pressure superconducting hydrides and ice with nuclear-electronic orbital theory".

  PublisherDOI

• Initialization with a Fock State Cavity Mode in Real-Time Nuclear-Electronic Orbital Polariton Dynamics

  Zenodo (CERN European Organization for Nuclear Research) · 2026-04-09

  datasetOpen accessSenior author

  Dataset and supporting scripts for Initialization with a Fock State Cavity Mode in Real-Time Nuclear-Electronic Orbital Polariton Dynamics, JCP 2026.For any questions or concerns, please contact Millan Welman (mw3838@princeton.edu, or millan.welman@gmail.com if you are viewing this after 2027).

  PublisherDOI

• Concerted Proton–Electron Transfer Minimizes Substituent Effects on Adsorbed Phthalocyanine Electrocatalysis

  Journal of the American Chemical Society · 2026-02-16 · 2 citations

  articleOpen access

  Molecularly modified electrodes (MMEs) are potent electrocatalysts, but few principles exist for their rational design. Electrocatalysis by soluble molecules depends strongly on substituents that tune the catalyst redox potential (E1/2), but it is unclear if this parameter similarly impacts MME catalysis. Herein, we employ the hydrogen evolution reaction (HER) as a test case for comparing carbon-adsorbed cobalt phthalocyanine (CoPc/C) and cobalt hexadecafluoro-phthalocyanine (CoFPc/C). By correlating HER activity and voltammetric data to total Co surface concentration across a wide range of catalyst loadings, we find that only 5–25% of adsorbed Co sites contribute to the Co(II/I) redox wave and that this subpopulation poorly correlates with catalytic activity. Instead, in the low-loading limit, catalytic activity correlates linearly with the majority Co(II/I)-silent Co population, revealing per-site turnover frequency (TOF) values for HER. Despite a 230 mV difference in Co(II/I) redox potentials, CoPc/C and CoFPc/C display TOF values differing by less than a factor of 3 when compared over a wide potential range. Mechanistic studies point to an inner-sphere concerted proton–electron transfer step as rate-determining, suggesting that the Co–H bond dissociation free energy (BDFE) rather than the Co(II/I) E1/2 is thermodynamically relevant. Computational studies indicate that the fluoro-substituents lead to compensatory changes in Co(II/I) E1/2 and Co(I) basicity, leaving the Co–H BDFE largely unchanged between CoPc and CoFPc and thereby manifesting in similar catalytic rates. These results highlight the limited effect of E1/2-tuning on MME catalytic activity and motivate the development of methods to directly alter active site–substrate BDFE.

  PublisherOA PDFDOI

• Capturing nuclear quantum effects in high-pressure superconducting hydrides and ice with nuclear-electronic orbital theory

  Zenodo (CERN European Organization for Nuclear Research) · 2026-04-16

  datasetOpen accessSenior author

  This repository contains the needed input, output files, and associated data needed to reproduce the results from the paper, "Capturing nuclear quantum effects in high-pressure superconducting hydrides and ice with nuclear-electronic orbital theory".

  PublisherDOI

• Initialization with a Fock state cavity mode in real-time nuclear–electronic orbital polariton dynamics

  The Journal of Chemical Physics · 2026-04-14

  articleOpen accessSenior author

  Molecular polaritons have drawn great interest in recent years as a possible avenue for providing optical control over chemical dynamics. A central challenge in the field is to identify physical phenomena that require a quantum rather than a classical treatment of electrodynamics. In this work, we use our recently developed mean-field quantum (mfq) and full-quantum (fq) real-time nuclear-electronic orbital (RT-NEO) time-dependent density functional theory methods to simulate polaritonic dynamics for a molecule under vibrational strong coupling when a quantized cavity mode is initialized in a Fock state rather than a coherent state. Our previous work showed that a coherent state initial condition for the cavity mode leads to polariton formation for both the mfq-RT-NEO and fq-RT-NEO methods. Herein, we show that the mfq-RT-NEO method, which does not allow light-matter entanglement, does not predict polariton formation for a Fock state initial condition. Similar to the mfq-RT-NEO method, the fq-RT-NEO method does not predict oscillations of the cavity mode coordinate and molecular dipole operator expectation values for a Fock state initial condition. However, the fq-RT-NEO method does predict oscillations of the expectation values of even powers of these operators as well as light-matter entanglement, implicating polariton formation with a Fock state initial condition. All these observations can be explained with model systems. These results suggest that using a quantized cavity mode initial condition that does not have a direct analogy to an initial condition in classical electrodynamics can lead to physical phenomena that can only be described by a quantum treatment of the cavity mode.

  PublisherDOI

• Proton-Coupled Electron and Energy Transfer in Molecular Triads

  Accounts of Chemical Research · 2026-04-17

  articleOpen access1st authorCorresponding

  ConspectusElectrons and protons are the simplest particles in chemistry, and their transfers are among the most fundamental chemical reactions. It is increasingly recognized that these two particles often transfer in the same elementary kinetic step, resulting in the most common type of proton-coupled electron transfer (PCET). PCET has evolved from a curiosity to a major research field that is central to a broad range of processes in chemistry, biology, and materials science.PCET evolved from electron transfer, in both its experimental and theoretical origins. One wonders how the field would be different if it had been called electron-coupled proton transfer. This equivalent terminology illustrates that the proton is on equal footing to the electron, making PCET perhaps the simplest case where the quantum properties of both an electron and a nucleus need to be considered.The fundamental understanding of PCET in solution builds on the remarkably impactful theory of electron transfer (ET) developed by R. A. Marcus and others. At a basic level, ET theory is marked by a quadratic dependence of the reaction barrier on the reaction free energy (ΔG⧧ on ΔG°), with normal and ‘inverted’ regions separated by a barrierless region (ΔG⧧ = 0), plus an electronic coupling that determines the electron tunneling probability. The theory for PCET includes additional essential elements: the quantum mechanical treatment of the transferring proton(s) as tunneling particles, multiple channels corresponding to reactant and product electron–proton vibronic states, vibronic coupling rather than electronic coupling, and a distribution of proton donor–acceptor distances.Our recent studies of ultrafast intramolecular PCET in molecular triads were the first to demonstrate the corresponding free-energy dependence for PCET, including the inverted region. Inverted behavior was previously thought to be difficult to observe experimentally for PCET because it connects vibronic states rather than electronic states. Due to the more closely spaced vibronic state energy levels compared to electronic state energy levels, there is usually a nearly barrierless pair of reactant and product vibronic states that obviates the inverted region. For these molecular triads, however, the vibronic coupling is very small for the barrierless pair, allowing observation of the hallmark inverted region.While looking for ultrafast PCET, we discovered a new elementary chemical reaction that we denoted proton-coupled energy transfer (PCEnT). In PCEnT, proton transfer (PT) is coupled to electronic excitation energy transfer. As with PCET, PT is required for the reaction to be thermodynamically accessible. In our molecular triads, PT occurs within the phenol–pyridine acceptor unit, concerted with electron transfer to a photoexcited anthracene (PCET) or electronic excitation energy transfer from a photoexcited anthracene (PCEnT). The dominant reaction depends on the molecular substituents and reaction conditions. A theory for PCEnT with some of the same essential elements as PCET theory, along with some fundamental differences, has been developed and applied to a triad system.

  PublisherDOI

• Nuclear–electronic orbital quasiclassical trajectory method for vibrational spectroscopy

  The Journal of Chemical Physics · 2026-04-14

  articleOpen accessSenior author

  Simulations of vibrational spectra are important for interpreting experimental data as well as understanding molecular structure and dynamics. Herein, we present an approach for the efficient and accurate incorporation of anharmonicity into such simulations. Real-time nuclear-electronic orbital time-dependent density functional theory treats specified protons quantum mechanically on the same level as the electrons, propagating the electronic and protonic densities according to the time-dependent Schrödinger equation. This approach inherently includes the anharmonicity of the quantum protons and can be combined with Ehrenfest dynamics for the classical nuclei. Herein, this real-time nuclear-electronic orbital (NEO)-Ehrenfest approach is combined with the quasiclassical trajectory (QCT) approach for generating initial conditions that include the zero-point energy of the classical nuclei, thereby enabling sampling of the anharmonic regions of the potential energy surface. The resulting NEO-QCT approach is shown to capture the anharmonic heavy nuclear motion, as well as the anharmonicity of the quantum protons, for a series of molecular systems, including HCN, HNC, FHF-, CH2O, and HCOOH. The NEO-QCT method also captures the distinct spectral features of the formate-water complex (CHO2-⋅ H2O), including the redshifted and broadened OH stretch band due to strong anharmonicity arising from hydrogen bonding and coupling between the motions of the hydrogen nuclei and the heavy nuclei. The NEO-QCT method enables computationally practical simulations of vibrational spectra of molecules that exhibit significant anharmonicity and coupling between vibrational modes.

  PublisherDOI

• Conformationally gated multisite proton-coupled electron transfer in the ribonucleotide reductase <i>β</i> subunit

  Proceedings of the National Academy of Sciences · 2026-01-30 · 1 citations

  articleOpen accessSenior author

  Ribonucleotide reductase (RNR) is an essential enzyme that converts ribonucleotides into deoxyribonucleotides, enabling DNA synthesis and repair in all living organisms. Central to class Ia RNR activity is a long-range radical transport pathway spanning [Formula: see text]32 Å across the [Formula: see text] and [Formula: see text] subunits by a series of proton-coupled electron transfer (PCET) reactions. Although the collinear PCET reactions in the [Formula: see text] subunit have been extensively studied, the multisite, orthogonal PCET reactions in the [Formula: see text] subunit are less well understood. This work focuses on orthogonal PCET between the redox-active tryptophan, W48, and interfacial tyrosine, Y356, in the [Formula: see text] subunit. Multiscale modeling strategies are employed to explore this PCET reaction. The simulations show that radical transfer from W48 to Y356 is thermodynamically favorable and is likely to occur by electron transfer from Y356 to the W48 cationic radical in conjunction with proton transfer from Y356 to a glutamate, E52, which forms a hydrogen-bonding interaction with Y356 following oxidation of W48. The conformational gating motion of Y356 is shown to be critical for allowing this residue to participate in PCET with W48 in the [Formula: see text] subunit and with a tyrosine in the [Formula: see text] subunit. Application of vibronically nonadiabatic PCET theory highlights the significance of hydrogen tunneling and conformational motions that shorten the distance between Y356 and E52. This work demonstrates how conformational gating, hydrogen-bonding networks, and hydration at the [Formula: see text]/[Formula: see text] interface modulate PCET in RNR. These fundamental insights are also applicable to other biomolecular systems and may guide therapeutic and protein engineering applications.

  PublisherOA PDFDOI

• Capturing nuclear quantum effects in high-pressure superconducting hydrides and ice with nuclear–electronic orbital theory

  Proceedings of the National Academy of Sciences · 2026-05-21

  articleOpen accessSenior authorCorresponding

  Nuclear quantum effects are essential for correctly describing hydrogen-rich materials at high pressures. Superconducting hydrides and ice are prime examples of such systems, requiring the inclusion of lattice anharmonicity and nuclear quantum effects to correctly predict and describe the structures and phase transition pressures observed experimentally. Herein, we show that the nuclear–electronic orbital density functional theory (NEO-DFT) method, which treats specified nuclei quantum mechanically on the same level as the electrons, is capable of accurately describing nuclear quantum effects in superconducting hydrides and ice. NEO-DFT predicts the hydrogen-bond symmetrization pressure in H 3 S and D 3 S, benchmarking against the more expensive stochastic self-consistent harmonic approximation method, and predicts the correct symmetric Fm <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" overflow="scroll"> <mml:mrow> <mml:mover accent="true"> <mml:mrow> <mml:mn>3</mml:mn> </mml:mrow> <mml:mrow> <mml:mo stretchy="false">¯</mml:mo> </mml:mrow> </mml:mover> <mml:mi>m</mml:mi> </mml:mrow> </mml:math> structure for LaH 10 at a wide range of pressures. NEO-DFT also predicts the ice VIII to ice X phase transition pressures for H 2 O and D 2 O in agreement with experimental measurements. The accuracy, computational efficiency, and broad applicability of the NEO method opens the door for expanded large-scale studies into these types of systems.

  PublisherDOI

• Nuclear–electronic orbital second-order coupled cluster for excited states

  The Journal of Chemical Physics · 2026-01-27 · 2 citations

  articleOpen accessSenior author

  Excited-state methods within the nuclear-electronic orbital (NEO) framework have the potential to capture vibrational, electronic, and vibronic transitions in a single calculation. In the NEO approach, specified nuclei, typically protons, are treated quantum mechanically at the same level of theory as the electrons. Affordable excited-state NEO methods, such as time-dependent density functional theory, are limited to capturing the subset of excitations with single-excitation character, whereas existing methods that capture the full spectrum are limited in applicability due to their high computational cost. Herein, we introduce the excited-state variant of NEO coupled cluster with approximate second-order doubles (NEO-CC2) and its scaled-opposite-spin variant with electron-proton correlation scaling (NEO-SOS'-CC2). We benchmark this method for positronium hydride, where the electrons and positron are treated quantum mechanically, and find that NEO-CC2 deviates from exact results, but NEO-SOS'-CC2 can achieve near-quantitative accuracy by increasing the electron-positron correlation. Benchmarking NEO-CC2 and NEO-SOS'-CC2 on four different triatomic molecules with a quantum proton, we find that NEO-CC2 captures qualitatively correct vibrational features such as overtones and combination bands, as well as mixed electron-proton double excitations. Electron-proton correlation scaling that increases the excited-state correlation relative to the ground-state correlation improves the accuracy across all the molecular systems tested. Quantitative accuracy is not achieved due to a combination of finite basis set effects and incomplete description of excited-state electron-proton correlation. Nevertheless, NEO-SOS'-CC2 can describe single and mixed protonic and electronic excitations with accuracy approaching that of much more computationally intensive methods.

  PublisherOA PDFDOI

Awards & honors

• Willard Gibbs Medal Award (2021)
• Joseph O. Hirschfelder Prize in Theoretical Chemistry (2021)
• American Chemical Society Award in Theoretical Chemistry (20…
• Royal Society of Chemistry Bourke Award (2020)
• G. M. Kosolapoff Award (2019)