Probing Nonadiabaticity in the Proton-Coupled Electron Transfer Reaction Catalyzed by Soybean Lipoxygenase

Proton-coupled electron transfer (PCET) plays a vital role in many biological and chemical processes. PCET rate constant expressions are available for various well-defined regimes, and determining which expression is appropriate for a given system is essential for reliable modeling. Quantitative diagnostics have been devised to characterize the vibronic nonadiabaticity between the electron–proton quantum subsystem and the classical nuclei, as well as the electron–proton nonadiabaticity between the electrons and proton(s) within the quantum subsystem. Herein these diagnostics are applied to a model of the active site of the enzyme soybean lipoxygenase, which catalyzes a PCET reaction that exhibits unusually high deuterium kinetic isotope effects at room temperature. Both semiclassical and electronic charge density diagnostics illustrate vibronic and electron–proton nonadiabaticity for this PCET reaction, supporting the use of the Golden rule nonadiabatic rate constant expression with a specific form of the vibronic coupling. This type of characterization will be useful for theoretical modeling of a broad range of PCET processes

Nonadiabatic Dynamics of Photoinduced Proton-Coupled Electron Transfer: Comparison of Explicit and Implicit Solvent Simulations

Theoretical approaches for simulating the ultrafast dynamics of photoinduced proton-coupled electron transfer (PCET) reactions in solution are developed and applied to a series of model systems. These processes are simulated by propagating nonadiabatic surface hopping trajectories on electron–proton vibronic surfaces that depend on the solute and solvent nuclear coordinates. The PCET system is represented by a four-state empirical valence bond model, and the solvent is treated either as explicit solvent molecules or as a dielectric continuum, in which case the solvent dynamics is described in terms of two collective solvent coordinates corresponding to the energy gaps associated with electron and proton transfer. The explicit solvent simulations reveal two distinct solvent relaxation time scales, where the faster time scale relaxation corresponds to librational motions of solvent molecules in the first solvation shell, and the slower time scale relaxation corresponds to the bulk solvent dielectric response. The charge transfer dynamics is strongly coupled to both the fast and slow time scale solvent dynamics. The dynamical multistate continuum theory is extended to include the effects of two solvent relaxation time scales, and the resulting coupled generalized Langevin equations depend on parameters that can be extracted from equilibrium molecular dynamics simulations. The implicit and explicit solvent approaches lead to qualitatively similar charge transfer and solvent dynamics for model PCET systems, suggesting that the implicit solvent treatment captures the essential elements of the nonequilibrium solvent dynamics for many systems. A combination of implicit and explicit solvent approaches will enable the investigation of photoinduced PCET processes in a variety of condensed phase systems

Electrochemical Electron Transfer and Proton-Coupled Electron Transfer: Effects of Double Layer and Ionic Environment on Solvent Reorganization Energies

Electron transfer and proton coupled electron transfer (PCET) reactions at electrochemical interfaces play an essential role in a broad range of energy conversion processes. The reorganization energy, which is a measure of the free-energy change associated with solute and solvent rearrangements, is a key quantity for calculating rate constants for these reactions. We present a computational method for including the effects of the double layer and ionic environment of the diffuse layer in calculations of electrochemical solvent reorganization energies. This approach incorporates an accurate electronic charge distribution of the solute within a molecular-shaped cavity in conjunction with a dielectric continuum treatment of the solvent, ions, and electrode using the integral equations formalism polarizable continuum model. The molecule-solvent boundary is treated explicitly, but the effects of the electrode-double layer and double layer-diffuse layer boundaries, as well as the effects of the ionic strength of the solvent, are included through an external Green’s function. The calculated total reorganization energies agree well with experimentally measured values for a series of electrochemical systems, and the effects of including both the double layer and ionic environment are found to be very small. This general approach was also extended to electrochemical PCET and produced total reorganization energies in close agreement with experimental values for two experimentally studied PCET systems

Role of Proton Diffusion in the Nonexponential Kinetics of Proton-Coupled Electron Transfer from Photoreduced ZnO Nanocrystals

Experiments have suggested that photoreduced ZnO nanocrystals transfer an electron and a proton to organic radicals through a concerted proton-coupled electron transfer (PCET) mechanism. The kinetics of this process was studied by monitoring the decay of the absorbance that reflects the concentration of electrons in the conduction bands of the nanocrystals. Interestingly, this absorbance exhibited nonexponential decay kinetics that could not be explained by heterogeneities of the nanoparticles or electron content. To determine if proton diffusion from inside the nanocrystal to reactive sites on the surface could lead to such nonexponential kinetics, herein this process is modeled using kinetic Monte Carlo simulations. These simulations provide the survival probability of a proton hopping among bulk, subsurface, and surface sites within the nanocrystal until it reaches a reactive surface site where it transfers to an organic radical. Using activation barriers predominantly obtained from periodic density functional theory, the simulations reproduce the nonexponential decay kinetics. This nonexponential behavior is found to arise from the broad distribution of lifetimes caused by different types of subsurface and surface sites. The longer lifetimes are associated with the proton becoming temporarily trapped in a subsurface site that does not have direct access to a reactive surface site due to capping ligands. These calculations suggest that movement of the protons rather than the electrons dominate the nonexponential kinetics of the PCET reaction. Thus, the impact of both bulk and surface properties of metal-oxide nanoparticles on proton conductivity should be considered when designing heterogeneous catalysts

Role of Proton Diffusion in the Nonexponential Kinetics of Proton-Coupled Electron Transfer from Photoreduced ZnO Nanocrystals

Experiments have suggested that photoreduced ZnO nanocrystals transfer an electron and a proton to organic radicals through a concerted proton-coupled electron transfer (PCET) mechanism. The kinetics of this process was studied by monitoring the decay of the absorbance that reflects the concentration of electrons in the conduction bands of the nanocrystals. Interestingly, this absorbance exhibited nonexponential decay kinetics that could not be explained by heterogeneities of the nanoparticles or electron content. To determine if proton diffusion from inside the nanocrystal to reactive sites on the surface could lead to such nonexponential kinetics, herein this process is modeled using kinetic Monte Carlo simulations. These simulations provide the survival probability of a proton hopping among bulk, subsurface, and surface sites within the nanocrystal until it reaches a reactive surface site where it transfers to an organic radical. Using activation barriers predominantly obtained from periodic density functional theory, the simulations reproduce the nonexponential decay kinetics. This nonexponential behavior is found to arise from the broad distribution of lifetimes caused by different types of subsurface and surface sites. The longer lifetimes are associated with the proton becoming temporarily trapped in a subsurface site that does not have direct access to a reactive surface site due to capping ligands. These calculations suggest that movement of the protons rather than the electrons dominate the nonexponential kinetics of the PCET reaction. Thus, the impact of both bulk and surface properties of metal-oxide nanoparticles on proton conductivity should be considered when designing heterogeneous catalysts

Computational Insights into Five- versus Six-Coordinate Iron Center in Ferrous Soybean Lipoxygenase

Soybean lipoxygenase (SLO) serves as a prototype for fundamental understanding of hydrogen tunneling in enzymes. Its reactivity depends on the active site structure around a mononuclear, nonheme iron center. The available crystal structures indicate five-coordinate iron, while magnetic circular dichroism experiments suggest significant populations of both five-coordinate (5C) and six-coordinate (6C) iron in ferrous SLO. Quantum mechanical calculations of gas phase models produce only 6C geometries. Herein mixed quantum mechanical/molecular mechanical (QM/MM) calculations are employed to identify and characterize the 5C and 6C geometries. These calculations highlight the importance of the protein environment, particularly two Gln residues in a hydrogen-bonding network with Asn694, the ligand that can dissociate. This hydrogen-bonding network is similar in both geometries, but twisting of a dihedral angle in Asn694 moves its oxygen away from the iron in the 5C geometry. These insights are important for future simulations of SLO

Fundamental Insights into Proton-Coupled Electron Transfer in Soybean Lipoxygenase from Quantum Mechanical/Molecular Mechanical Free Energy Simulations

The proton-coupled electron transfer (PCET) reaction catalyzed by soybean lipoxygenase has served as a prototype for understanding hydrogen tunneling in enzymes. Herein this PCET reaction is studied with mixed quantum mechanical/molecular mechanical (QM/MM) free energy simulations. The free energy surfaces are computed as functions of the proton donor–acceptor (C–O) distance and the proton coordinate, and the potential of mean force is computed as a function of the C–O distance, inherently including anharmonicity. The simulation results are used to calculate the kinetic isotope effects for the wild-type enzyme (WT) and the L546A/L754A double mutant (DM), which have been measured experimentally to be ∼80 and ∼700, respectively. The PCET reaction is found to be exoergic for WT and slightly endoergic for the DM, and the equilibrium C–O distance for the reactant is found to be ∼0.2 Å greater for the DM than for WT. The larger equilibrium distance for the DM, which is due mainly to less optimal substrate binding in the expanded binding cavity, is primarily responsible for its higher kinetic isotope effect. The calculated potentials of mean force are anharmonic and relatively soft at shorter C–O distances, allowing efficient thermal sampling of the shorter distances required for effective hydrogen tunneling. The primarily local electrostatic field at the transferring hydrogen is ∼100 MV/cm in the direction to facilitate proton transfer and increases dramatically as the C–O distance decreases. These simulations suggest that the overall protein environment is important for conformational sampling of active substrate configurations aligned for proton transfer, but the PCET reaction is influenced primarily by local electrostatic effects that facilitate conformational sampling of shorter proton donor–acceptor distances required for effective hydrogen tunneling