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.

Time-resolved spectroscopy is an important tool for probing photochemically induced nonequilibrium dynamics and energy transfer. Herein, a method is developed for the ab initio simulation of vibronic spectra and dynamical processes. This framework utilizes the recently developed nuclear–electronic orbital time-dependent configuration interaction (NEO-TDCI) approach, which treats all electrons and specified nuclei quantum mechanically on the same footing. A strategy is presented for calculating time-resolved vibrational and electronic absorption spectra from any initial condition. Although this strategy is general for any TDCI implementation, utilizing the NEO framework allows for the explicit inclusion of quantized nuclei, as illustrated through the calculation of vibrationally hot spectra. Time-resolved spectra produced by either vibrational or electronic Rabi oscillations capture ground-state absorption, stimulated emission, and excited-state absorption between vibronic states. This methodology provides the foundation for fully ab initio simulations of multidimensional spectroscopic experiments.

Proton-coupled electron transfer (PCET) plays a vital role in a wide range of electrochemical processes. This talk will describe theoretical and computational methods that have been developed to study electrochemical PCET and a variety of applications to molecular and heterogeneous electrocatalysis. My group has formulated a general PCET theory that includes the quantum mechanical effects of the electrons and transferring protons, as well as the motions of the donor-acceptor modes and solvent or protein environment. This PCET theory enables the calculation of rate constants and kinetic isotope effects for comparison to experiment. Our extension of this theory to electrochemical PCET incorporates the electronic structure of the electrode and the interfacial electric fields arising from the electrical double layer. Theoretical formulations for both homogeneous and heterogeneous electrochemical PCET provide analytical expressions for the rate constants and current densities as functions of applied potential. This theory has been applied to proton discharge on metal electrodes, as well as PCET at metal oxides and graphite-conjugated catalysts. These applications highlight the importance of using a theory that quantizes the transferring proton and includes the effects of hydrogen tunneling and excited electron-proton vibronic states. The insights from these theoretical studies are useful for the design of electrocatalytic systems to control the movement and coupling of electrons and protons for energy conversion processes. References Venkataraman, A. V. Soudackov, and S. Hammes-Schiffer, Theoretical formulation of nonadiabatic electrochemical proton-coupled electron transfer at metal-solution interfaces, J. Phys. Chem. C 112 , 12386-12397 (2008). K. Goldsmith, Y. C. Lam, A V. Soudackov, and S. Hammes-Schiffer, Proton discharge on a gold electrode from triethylammonium in acetonitrile: Theoretical modeling of potential-dependent kinetic isotope effects, J. Am. Chem. Soc. 141 , 1084-1090 (2019). C. Lam, A. V. Soudackov, and S. Hammes-Schiffer, Kinetics of proton discharge on metal electrodes: Effects of vibrational nonadiabaticity and solvent dynamics, J. Phys. Chem. Lett. 10 , 5312-5217 (2019). E. Warburton, P. Hutchison, M. N. Jackson, M. L. Pegis, Y. Surendranath, and S. Hammes-Schiffer, “Interfacial field-driven proton-coupled electron transfer at graphite-conjugated organic acids,” J. Am. Chem. Soc. 142 , 20855-20864 (2020). E. Warburton, A. V. Soudackov, and S. Hammes-Schiffer, Theoretical modeling of electrochemical proton-coupled electron transfer, Chem. Rev. 122 , 10599-10650 (2022).

Ribonucleotide reductase (RNR) is essential for DNA synthesis and repair in all living organisms. The mechanism of E. coli RNR requires long-range radical transport through a proton-coupled electron transfer (PCET) pathway spanning two different protein subunits. Herein, the direct PCET reaction between the interfacial tyrosine residues, Y356 and Y731, is investigated with a vibronically nonadiabatic theory that treats the transferring proton and all electrons quantum mechanically. The input quantities to the PCET rate constant expression are computed with a combination of density functional theory and molecular dynamics simulations. The calculations highlight the importance of hydrogen tunneling in this PCET reaction. Compression of the distance between the proton donor and acceptor oxygen atoms of the interfacial tyrosine residues is essential to facilitate hydrogen tunneling by increasing the overlap between the reactant and product proton vibrational wave functions. This compression occurs by thermal conformational fluctuations of these interfacial tyrosine residues. N733 and R411 are identified as key residues that can hydrogen bond to Y731 and Y356, respectively, and thereby compete with the hydrogen-bonding interaction between Y731 and Y356 required for direct PCET. Understanding the roles of hydrogen tunneling and conformational motions in this interfacial PCET reaction, as well as identifying other residues that may impact the kinetics, is important for targeted protein engineering efforts to modulate RNR activity.

The design of catalysts capable of functionalizing unactivated C(sp3)-H bonds remains a significant goal in synthetic organic chemistry. Herein, we present a novel set of iridium polypyridyl complexes bearing pendent Brønsted basic carboxylates that become potent hydrogen atom abstraction catalysts upon visible light irradiation. Thermochemical and spectroscopic characterization reveal that these excited-state complexes exhibit bond dissociation free energies (BDFEs) of up to 105 kcal mol-1 with long excited-state lifetimes. We demonstrate that these complexes can catalyze C-H alkylation reactions in which the Ir carboxylate mediates both C-H abstraction and formation steps. Mechanistic, spectroscopic, and computational studies are consistent with C-H abstraction proceeding through an excited-state proton-coupled electron transfer (PCET) step. The modular nature of these Ir polypyridyl complexes establishes a foundation for designing tunable and efficient C-H functionalization catalysts based on covalent tethering of excited-state oxidants and bases.

Molecular polaritons are hybrid light-matter states that enable the exploration of potential cavity-modified chemistry. The development of dynamical, first-principles approaches for simulating molecular polaritons is important for understanding their origins and properties. Herein, we present a hierarchy of first-principles methods to simulate the real-time dynamics of molecular polaritons in the strong coupling regime. These methods are based on real-time time-dependent density functional theory (RT-TDDFT) and the corresponding real-time nuclear-electronic orbital (RT-NEO) approach, in which specified nuclei are treated quantum mechanically on the same level as the electrons. The hierarchy spans semiclassical, mean-field quantum, and full-quantum approaches to simulate polariton dynamics under both electronic strong coupling and vibrational strong coupling. In the semiclassical approaches, the cavity mode is treated classically, whereas in the full-quantum approaches, the cavity mode is treated quantum mechanically with propagation of a joint molecule-mode density matrix. The semiclassical and full-quantum approaches produce virtually identical Rabi splittings and polariton peak locations for the systems studied. However, the full-quantum approaches allow exploration of molecule-mode quantum entanglement in real-time dynamics. Although the degree of light-matter entanglement is relatively small in the systems considered, the oscillations of the von Neumann entropy reveal an entanglement Rabi splitting that differs from the Rabi splitting computed from the time-dependent dipole moment. These results suggest that a classical treatment of the cavity mode may provide an excellent description of polariton dynamics for macroscopic observables such as the Rabi splitting, but novel physics may be detectable by considering molecule-mode entanglement.

Real-time nuclear-electronic orbital Ehrenfest (RT-NEO-Ehrenfest) dynamics methods provide a first-principles approach for describing nonadiabatic molecular processes with nuclear quantum effects. For an efficient description of proton transfer within RT-NEO-Ehrenfest dynamics, the basis function center associated with the quantum proton can be allowed to move classically. This traveling proton basis (TPB) approach effectively captures proton quantum dynamics, although its energy conservation behavior is not yet fully satisfactory. Two recently proposed TPB approaches, in principle, conserve the extended energy, which includes both the system energy and the kinetic energy associated with the proton basis function center. Herein, a thermostatted TPB approach is proposed to improve the conservation of the system energy, excluding the kinetic energy associated with the proton basis function center. In this approach, the quantum proton dynamics are modulated by dynamically rescaling the proton momentum operator to maintain the system energy conservation. With the excited-state intramolecular proton transfer of o-hydroxybenzaldehyde as an example, this approach is shown to significantly improve the system energy conservation while preserving the accuracy of the quantum proton dynamics as achieved in the original TPB approach.

Investigating water structures at aqueous interfaces has been a central focus in the field of nonlinear surface spectroscopy over decades. This large body of work leads to a conclusion that asymmetric OH stretches should be largely silent in sum frequency generation (SFG) spectra. Nonetheless, our recent studies show chiral-specific SFG response of water originating from the first hydration shell of proteins and DNA arising from a sum of equal-magnitude and opposite-phase symmetric and asymmetric OH stretches, resulting in an oppositely signed couplet. Motivated initially by this apparently inconsistent behavior for chiral-specific vs conventional (achiral) SFG, we demonstrate herein a fundamental argument for the appearance of the oppositely signed couplets in chiral-specific vibrational SFG. The interplay between two foundational optical relations, Kramers-Kronig relations and index-interchange symmetry arising in the adiabatic zero-frequency limit (often referred to as Kleinman symmetry), is shown to require the imaginary resonant contributions to the tensors describing chiral-specific SFG responses to collectively sum to zero. In brief, all indices within the surface susceptibility must become interchangeable in the degenerate, zero-frequency adiabatic limit. From Kramers-Kronig relations connecting the real and imaginary susceptibility, this asymptotic limit in the real susceptibility can only be met if the imaginary-valued resonant contributions over the relevant spectral range sum to zero. These symmetry constraints were found to agree with density functional theory calculations on small water clusters and with experimental and computational phase-resolved chiral-specific SFG spectra. These symmetry requirements provide constraints for analyzing phase-resolved chiral-specific SFG spectra for extracting structural information about chiral molecules at interfaces.

Hydrogen tunneling is an important process that impacts reaction rates and molecular spectra. Describing and understanding this process requires a quantum mechanical treatment of the transferring hydrogen. The nuclear-electronic orbital (NEO) approach treats specified nuclei quantum mechanically on the same level as electrons and has recently been implemented at the multireference configuration interaction (MRCI) wavefunction level. The NEO-MRCI method includes both the static correlation necessary to describe hydrogen tunneling and the electron-proton dynamic correlation required for computing quantitatively accurate nuclear-electronic vibronic states. Herein, the NEO-MRCI method is used to compute the nuclear-electronic wavefunctions and corresponding vibronic energies for four hydrogen tunneling systems at fixed geometries for a range of donor-acceptor distances. Comparison of the NEO-MRCI results to numerically exact grid-based calculations shows that the NEO-MRCI method can be used to obtain accurate hydrogen and deuterium tunneling splittings at fixed geometries. Thus, this work presents an important component for studying hydrogen tunneling systems.

ConspectusProton-coupled electron transfer (PCET) is essential for a wide range of chemical and biological processes. Understanding the mechanism of PCET reactions is important for controlling and tuning these processes. The kinetic isotope effect (KIE), defined as the ratio of the rate constants for hydrogen and deuterium transfer, is used to probe PCET mechanisms experimentally but is often challenging to interpret. Herein, a theoretical framework is described for interpreting KIEs of concerted PCET reactions. The first step is to classify the reaction in terms of vibronic and electron-proton nonadiabaticities, which reflect the relative time scales of the electrons, protons, and environment. The second step is to select the appropriate rate constant expression based on this classification. The third step is to compute the input quantities with computational methods.Vibronically adiabatic PCET reactions occur on the electronic and vibrational ground state and can be described within the transition state theory framework. The nuclear-electronic orbital (NEO) method, which treats specified protons quantum mechanically on the same level as the electrons, can be used to generate the electron-proton vibronic free energy surface for hydrogen and deuterium and to compute the corresponding free energy barriers. Such reactions typically exhibit moderate KIEs that arise from zero-point energy and shallow tunneling effects.Vibronically nonadiabatic PCET reactions involve excited electron-proton vibronic states and can be described with a golden rule formalism corresponding to nonadiabatic transitions between pairs of reactant and product vibronic states. Such reactions can exhibit KIEs ranging from unity, or even slightly less than unity, to more than 500. These KIEs can be explained in terms of multiple, competing reaction pathways corresponding to electron and proton tunneling between different pairs of vibronic states. The tunneling probability is determined by the vibronic coupling, which can be computed using a general expression but often is proportional to the overlap between the reactant and product proton vibrational wave functions. In this regime, the KIE is influenced by the vibronic couplings, the proton donor-acceptor equilibrium distance and motion, and contributions from excited vibronic states.Three illustrative examples of vibronically nonadiabatic PCET are discussed. The unusually large KIEs in soybean lipoxygenase of ∼80 for the wild-type enzyme and ∼700 for a double mutant are explained in terms of a large equilibrium proton donor-acceptor distance and nonoptimal orientation, leading to a small overlap between vibrational wave functions and therefore a large difference in hydrogen and deuterium tunneling probabilities. The KIEs for benzimidazole-phenol molecules ranging from unity to moderate are explained in terms of the dominance of different pairs of vibronic states with different vibrational wave function overlaps. The potential-dependent KIE observed for proton discharge from triethylammonium acid to a gold surface in acetonitrile is explained in terms of different pairs of vibronic states contributing for hydrogen and deuterium, with the reaction channels exhibiting different dependencies on the applied potential. These examples show that the KIE can vary widely, depending on which pairs of vibronic states dominate and their corresponding vibronic couplings. This work has broad implications for the interpretation of experimentally measured KIEs of PCET reactions.

Accurate pKa prediction is critical for understanding chemical reactivity and molecular properties across a wide range of applications. Computational approaches usually invoke a harmonic treatment of the vibrational modes for zero-point energies, as well as thermal and entropic contributions. Herein, we present a general protocol for relative pKa prediction that incorporates the significant anharmonic effects using nuclear-electronic orbital (NEO) theory. This protocol is validated against experimental data for a range of molecules in acetonitrile, including protonated nitrogen bases, nitrophenols, anilines, and diamines, as well as cobalt electrocatalysts. For simple acids, the NEO approach offers only a slight improvement over conventional density functional theory with the standard harmonic vibrational treatment, whereas for hydrogen-bonded acids, the NEO approach offers more significantly improved performance at a comparable computational cost. This accessible methodology provides a practical route for accurate pKa prediction in challenging systems and is extendable to related thermodynamic properties such as hydricities and proton-coupled redox potentials.

Knowledge of how intermolecular interactions change hydration structures surrounding DNA will heighten understanding of DNA biology and advance drug development. However, probing changes in DNA hydration structures in response to molecular interactions and drug binding in situ under ambient conditions has remained challenging. Here, we apply a combined experimental and computational approach of chiral-selective vibrational sum frequency generation spectroscopy (chiral SFG) to probe changes of DNA hydration structures when a small-molecule drug, netropsin, binds the minor groove of DNA. Our results show that chiral SFG can detect water being displaced from the minor groove of DNA due to netropsin binding. Additionally, we observe that chiral SFG distinguishes between weakly and strongly hydrogen-bonded water hydrating DNA. Chiral SFG spectra show that netropsin binding, instead of displacing weakly hydrogen-bonded water, preferentially displaces water molecules strongly hydrogen-bonded to thymine carbonyl groups in the DNA minor groove, revealing the roles of water in modulating site-specificity of netropsin binding to duplex DNA rich in adenine-thymine sequences. The results convey the promise of chiral SFG to offer mechanistic insights into roles of water in drug development targeting DNA.

The nuclear-electronic orbital (NEO) approach incorporates nuclear quantum effects into quantum chemistry calculations by treating specified nuclei quantum mechanically, equivalently to the electrons. Within the NEO framework, excited states are vibronic states representing electronic and nuclear vibrational excitations. The NEO multireference configuration interaction (MRCI) method presented herein provides accurate ground and excited vibronic states. The electronic and nuclear orbitals are optimized with a NEO multiconfigurational self-consistent field (NEO-MCSCF) procedure, thereby including both static and dynamic correlation and allowing the description of double and higher excitations. The accuracy of the NEO-MRCI method is illustrated by computing the ground state protonic densities and excitation energies of the vibronic states for four molecular systems with the hydrogen nucleus treated quantum mechanically. In addition, revised conventional electronic basis sets adapted for quantized nuclei are developed and shown to be essential for achieving this level of accuracy. The NEO-MRCI approach, as well as the strategy for revising electronic basis sets, will play a critical role in multicomponent quantum chemistry.

Harnessing a static magnetic field to drive molecular vibrations presents a promising avenue for controlling chemical processes. However, the coupling of nuclear dynamics with an external magnetic field has largely been explored only through classical approximations. In this work, we introduce a time-dependent quantum dynamics formalism based on London nuclear-electronic orbitals, enabling the simulation of magnetic field-driven quantum dynamics. Through simulations of HCN and H2CO molecules, we provide a detailed analysis of how the relative orientation of the magnetic field and vibrational symmetry influence the resulting quantum dynamics. Our findings reveal field-induced mode couplings and symmetry-dependent effects, offering new insights into the role of magnetic fields in vibrational control. This work establishes a quantum mechanical framework for understanding and manipulating vibrational dynamics using external magnetic fields, paving the way for novel applications in spectroscopy, reaction dynamics, and quantum control.

Proton-coupled electron transfer (PCET) is pervasive throughout chemistry, biology, and physics. Over the last few decades, we have developed a general theoretical formulation for PCET that includes the quantum mechanical effects of the electrons and transferring protons, including hydrogen tunneling, as well as the reorganization of the environment and the donor-acceptor fluctuations. Analytical rate constants have been derived in various well-defined regimes. This Tutorial focuses on the vibronically nonadiabatic regime, in which a golden rule rate constant expression is applicable. The goal is to provide detailed instructions on how to compute the input quantities to this rate constant expression for PCET in molecules, proteins, and electrochemical systems. The required input quantities are the inner-sphere and outer-sphere reorganization energies, the diabatic proton potential energy profiles, the electronic coupling, the reaction free energy, and the proton donor-acceptor distance distribution function. Instructions on how to determine the degree of electron-proton nonadiabaticity, which is important for determining the form of the vibronic coupling, are also provided. Detailed examples are given for thermal enzymatic PCET, homogeneous molecular electrochemical PCET, photochemical molecular PCET, and heterogeneous electrochemical PCET. A Python-based package, pyPCET, for computing nonadiabatic PCET rate constants, along with example scripts, input data, output files, and detailed documentation, is publicly available.

Polaritons have gained significant attention for the tantalizing possibility of modifying chemical properties and dynamics by coupling molecules to resonant cavity modes to create hybrid light-matter quantum states. Herein, we implement the semiclassical nuclear-electronic orbital time-dependent configuration interaction (NEO-TDCI) approach, which treats electrons and specified nuclei on the same quantum mechanical level, while treating the cavity mode classically. This ab initio dynamics approach can describe both the electronic strong coupling and the vibrational strong coupling regimes at the same level of theory without invoking the Born-Oppenheimer separation between the quantum nuclei and the electrons. This approach is used to simulate resonant and off-resonant vibronic strong coupling, where the cavity mode couples to one or many vibronic transitions associated with joint electronic-nuclear excitations within a vibronic progression. In this case, the cavity mode couples to nuclear motions even for cavity frequencies typically associated with electronic strong coupling. This approach is also used to illustrate that coupling a molecule to a cavity mode can alter hydrogen tunneling dynamics. The semiclassical NEO-TDCI approach provides the foundation for investigating how polaritons may be able to influence chemical reactions involving tunneling and nonadiabatic effects.

Proton-coupled energy transfer (PCEnT) refers to a photochemical process in which the transfer of electronic excitation energy between donor and acceptor molecules is coupled to a proton transfer reaction. Herein, we apply our recently developed nonadiabatic PCEnT theory to an anthracene-phenol-pyridine triad system. For this system, electronic excitation energy is transferred from the anthracene to the phenol-pyridine, in conjunction with proton transfer from the phenol to the pyridine. Thus, the PCEnT reaction corresponds to the transition from the local excited state of the anthracene (LES) to the local electron-proton transfer (LEPT) state of the phenol-pyridine. With most input quantities determined from first-principles calculations, our theory reproduces the experimentally measured PCEnT rate constant. We analyzed the contributions from different electron-proton vibronic states to the PCEnT rate constant (the LES to LEPT state) and the acceptor absorption spectrum (the ground state to LEPT state). For the triad, PCEnT occurs in the absence of detectable spectral overlap between the donor emission and acceptor absorption spectra, even though conventional energy transfer theories require adequate spectral overlap. In this case, the LEPT vibronic state that dominates the PCEnT process contributes negligibly to the acceptor absorption spectrum due to the small Franck-Condon overlap associated with proton transfer. Energy transfer in PCEnT requires accompanying proton transfer to lower the energy of the LEPT state and enable sufficient spectral overlap that overcomes the small proton vibrational wave function overlap associated with proton transfer. This work enhances fundamental understanding of the PCEnT process and provides guidance for the design of other types of PCEnT systems.

Colloidal gold nanoparticles (AuNPs) have myriad scientific and technological applications, but their fundamental redox chemistry is underexplored. Reported here are titration studies of oxidation and reduction reactions of aqueous AuNP colloids, which show that the AuNPs bind substantial hydrogen (electrons + protons) under mild conditions. The 5 nm AuNPs are reduced to a similar extent with reductants from borohydrides to H-2 and are reoxidized back essentially to their original state by oxidants, including O-2. The reactions were monitored via surface plasmon resonance (SPR) optical absorption, which was shown to be much more sensitive to surface H than to changes in solution conditions. Reductions with H-2 occurred without pH changes, demonstrating that hydrogenation forms surface H rather than releasing H+. Computational studies suggested that an SPR blueshift was expected for H atom addition, while just electron addition likely would have caused a redshift. Titrations consistently showed a maximum redox change of the 5 nm NPs, independent of the reagent, corresponding to 9% of the total gold or similar to 30% hydrogen surface coverage (similar to 370 H per AuNP). Larger AuNPs showed smaller maximum fractional surface coverages. We conclude that H binds to the edge, corner, and defect sites of the AuNPs, which explains the stoichiometric limitation and the size effect. The finding of substantial and stable hydrogen on the AuNP surface under mild reducing conditions has potential implications for various applications of AuNPs in reducing environments, from catalysis to biomedicine. This finding contrasts with the behavior of bulk gold and with the typical electron-focused perspective in this field.

Unusual nuclear quantum effects may emerge near noble metal nanostructures such as squeezed vibrational states in molecular junctions and plasmonic resonance energy transfer in the infrared domain. Herein, nuclear quantum effects near heavy metals are studied by nuclear-electronic orbital density functional theory (NEO-DFT) with an effective core potential. For a quantum proton sandwiched between a pair of gold tips modeled by two Au6 clusters, NEO-DFT calculations suggest that the quantum proton density can be squeezed as the tip distance decreases. For an HF molecule placed near a one-dimensional Au nanowire composed of up to 34 Au atoms, real-time NEO time-dependent density functional theory (RT-NEO-TDDFT) shows that the infrared plasmonic motion within the Au nanowire may resonantly transfer electronic energy to the HF proton vibrational stretch mode. Overall, these calculations illustrate the advantages of the NEO approach for probing nuclear quantum effects, such as squeezed proton vibrational states and infrared plasmonic resonance energy transfer.

We present a Lagrangian-based implementation of Ehrenfest dynamics with nuclear-electronic orbital (NEO) theory and real-time time-dependent density functional theory for extended periodic systems. In addition to a quantum dynamical treatment of electrons and selected protons, this approach allows for the classical movement of all other nuclei to be taken into account in simulations of condensed matter systems. Furthermore, we introduce a Lagrangian formulation for the traveling proton basis approach and propose new schemes to enhance its application for extended periodic systems. Validation and proof-of-principle applications are performed on electronically excited proton transfer in the o-hydroxybenzaldehyde molecule with explicit solvating water molecules. These simulations demonstrate the importance of solvation dynamics and a quantum treatment of transferring protons. This work broadens the applicability of the NEO Ehrenfest dynamics approach for studying complex heterogeneous systems in the condensed phase.