Calculation of Electrochemical Reorganization Energies for Redox Molecules at Self-Assembled Monolayer Modified Electrodes

Electrochemical electron transfer reactions play an important role in energy conversion processes with many technological applications. Electrodes modified by self-assembled monolayers (SAMs) exhibit reduced double layer effects and are used in molecular electronics. An important quantity for calculating the electron transfer rate constant is the reorganization energy, which is associated with changes in the solute geometry and the environment. In this Letter, an approach for calculating the electrochemical reorganization energy for a redox molecule attached to or near a SAM modified electrode is presented. This integral equations formalism polarizable continuum model (IEF-PCM) approach accounts for the detailed electronic structure of the molecule, as well as the contributions from the electrode, SAM, and electronic and inertial solvent responses. The calculated total reorganization energies are in good agreement with experimental data for a series of metal complexes in aqueous solution. This approach will be useful for calculating electron transfer rate constants for molecular electrocatalysts

Multidimensional Quantum Dynamical Simulation of Infrared Spectra under Polaritonic Vibrational Strong Coupling

Recent experimental and theoretical studies demonstrate that the chemical reactivity of molecules can be modified inside an optical cavity. Here, we provide a theoretical framework for conducting multidimensional quantum simulations of the infrared (IR) spectra for molecules interacting with cavity modes. A single water molecule under polaritonic vibrational strong coupling serves as an illustrative example. Combined with accurate potential energy and dipole moment surfaces, our cavity vibrational self-consistent field/virtual state configuration interaction (cav-VSCF/VCI) approach can predict the IR spectra when the molecule is inside or outside the cavity. The spectral signatures of Rabi splittings and shifts of certain bands are found to be strongly dependent on the frequency and polarization direction of the cavity modes. Analyses of the simulated spectra show that polaritonic vibrational strong coupling can induce unconventional couplings among the molecule’s vibrational modes, suggesting that intramolecular vibrational energy transfer can be significantly accelerated by the cavity

Role of Solvent Dynamics in Photoinduced Proton-Coupled Electron Transfer in a Phenol–Amine Complex in Solution

Photoinduced proton-coupled electron transfer (PCET) plays an essential role in a wide range of energy conversion processes. Previous experiments on a phenol–amine complex in solution provided evidence of an electron–proton transfer (EPT) excited state characterized by both intramolecular charge transfer and proton transfer from the phenol to the amine. Herein we analyze hundreds of surface hopping trajectories to investigate the role of solvent dynamics following photoexcitation to the EPT state. This solvent dynamics leads to a significant decrease in the energy gap between the ground and EPT states, thereby facilitating decay to the ground state, and generates an electrostatic environment conducive to proton transfer on the EPT state. In addition to solvent reorganization, the geometrical properties at the hydrogen-bonding interface must be suitable to allow proton transfer. These mechanistic insights elucidate the underlying fundamental physical principles of photoinduced PCET processes

Charge-Transfer Excited States and Proton Transfer in Model Guanine-Cytosine DNA Duplexes in Water

Characterization of the excited electronic states and relaxation processes in DNA systems is critical for understanding the physical basis of radiation damage. Spectroscopic studies have shown evidence of coupling between the relaxation dynamics of photoinduced charge-transfer states and interstrand proton transfer in DNA duplexes, where a deuterium isotope effect was observed for duplexes with alternating sequences but not with nonalternating sequences. We performed quantum mechanical/molecular mechanical (QM/MM) calculations of the vertical excitation energies and excited state proton potential energy curves for model DNA duplexes comprised of three guanine-cytosine pairs with alternating and nonalternating sequences in aqueous solution. Our calculations indicate that the intrastrand charge-transfer states are lower in energy for the alternating sequence than for the nonalternating sequence. The more accessible intrastrand charge-transfer states could provide a relaxation pathway coupled to interstrand proton transfer, thereby providing a possible explanation for the experimentally observed deuterium isotope effect in duplexes with alternating sequences

Tuning the Ultrafast Dynamics of Photoinduced Proton-Coupled Electron Transfer in Energy Conversion Processes

Photoinduced proton-coupled electron transfer (PCET) is essential for a wide range of energy conversion processes in chemical and biological systems. Understanding the underlying principles of photoinduced PCET at a level that allows tuning and control of the ultrafast dynamics is crucial for designing renewable and sustainable energy sources such as artificial photosynthesis devices and photoelectrochemical cells. This Perspective discusses fundamental aspects of photoinduced PCET, including the characterization of different types of excited electronic states, as well as the roles of solute and solvent dynamics, nonadiabatic transitions, proton delocalization, and vibrational relaxation. It also presents strategies for tuning and controlling the charge transfer dynamics and relaxation processes by altering the nature and positions of molecular substituents, the distance associated with electron transfer, the proton transfer interface, and the solvent properties. These insights, in conjunction with further studies, will play an important role in guiding the design of more effective energy conversion devices

Effects of Active Site Mutations on Specificity of Nucleobase Binding in Human DNA Polymerase η

Human DNA polymerase η (Pol η) plays a vital role in protection against skin cancer caused by damage from ultraviolet light. This enzyme rescues stalled replication forks at cyclobutane thymine–thymine dimers (TTDs) by inserting nucleotides opposite these DNA lesions. Residue R61 is conserved in the Pol η enzymes across species, but the corresponding residue, as well as its neighbor S62, is different in other Y-family polymerases, Pol ι and Pol κ. Herein, R61 and S62 are mutated to their Pol ι and Pol κ counterparts. Relative binding free energies of dATP to mutant Pol η•DNA complexes with and without a TTD were calculated using thermodynamic integration. The binding free energies of dATP to the Pol η•DNA complex with and without a TTD are more similar for all of these mutants than for wild-type Pol η, suggesting that these mutations decrease the ability of this enzyme to distinguish between a TTD lesion and undamaged DNA. Molecular dynamics simulations of the mutant systems provide insights into the molecular level basis for the changes in relative binding free energies. The simulations identified differences in hydrogen-bonding, cation−π, and π–π interactions of the side chains with the dATP and the TTD or thymine–thymine (TT) motif. The simulations also revealed that R61 and Q38 act as a clamp to position the dATP and the TTD or TT and that the mutations impact the balance among the interactions related to this clamp. Overall, these calculations suggest that R61 and S62 play key roles in the specificity and effectiveness of Pol η for bypassing TTD lesions during DNA replication. Understanding the basis for this specificity is important for designing drugs aimed at cancer treatment

Substituent Effects on Cobalt Diglyoxime Catalysts for Hydrogen Evolution

The design of efficient, robust, and inexpensive hydrogen evolution catalysts is important for the development of renewable energy sources such as solar cells. Cobalt diglyoxime complexes, Co(dRgBF₂)₂ with substituents R, are promising candidates for such electrocatalysts. The mechanism for hydrogen production requires a series of reduction and protonation steps for various monometallic and bimetallic pathways. In this work, the reduction potentials and p<i>K</i>_a values associated with the individual steps were calculated for a series of substituents. The calculations revealed a linear relation between the reduction potentials and p<i>K</i>_a values with respect to the Hammett constants, which quantify the electron donating or withdrawing character of the substituents. Additionally, the reduction potentials and p<i>K</i>_a values are linearly correlated with each other. These linear correlations enable the prediction of reduction potentials and p<i>K</i>_a values, and thus the free energy changes along the reaction pathways, to assist in the design of more effective cobaloxime catalysts

Exploring the Role of the Third Active Site Metal Ion in DNA Polymerase η with QM/MM Free Energy Simulations

The enzyme human DNA polymerase η (Pol η) is critical for bypassing lesions during DNA replication. In addition to the two Mg²⁺ ions aligning the active site, experiments suggest that a third Mg²⁺ ion could play an essential catalytic role. Herein the role of this third metal ion is investigated with quantum mechanical/molecular mechanical (QM/MM) free energy simulations of the phosphoryl transfer reaction and a proposed self-activating proton transfer from the incoming nucleotide to the pyrophosphate leaving group. The simulations with only two metal ions in the active site support a sequential mechanism, with phosphoryl transfer followed by relatively fast proton transfer. The simulations with three metal ions in the active site suggest that the third metal ion may play a catalytic role through electrostatic interactions with the leaving group. These electrostatic interactions stabilize the product, making the phosphoryl transfer reaction more thermodynamically favorable with a lower free energy barrier relative to the activated state corresponding to the deprotonated 3′OH nucleophile, and also inhibit the subsequent proton transfer. The possibility that Mg²⁺-bound hydroxide acts as the base deprotonating the 3′OH nucleophile is also explored

Calculation of Vibrational Shifts of Nitrile Probes in the Active Site of Ketosteroid Isomerase upon Ligand Binding

The vibrational Stark effect provides insight into the roles of hydrogen bonding, electrostatics, and conformational motions in enzyme catalysis. In a recent application of this approach to the enzyme ketosteroid isomerase (KSI), thiocyanate probes were introduced in site-specific positions throughout the active site. This paper implements a quantum mechanical/molecular mechanical (QM/MM) approach for calculating the vibrational shifts of nitrile (CN) probes in proteins. This methodology is shown to reproduce the experimentally measured vibrational shifts upon binding of the intermediate analogue equilinen to KSI for two different nitrile probe positions. Analysis of the molecular dynamics simulations provides atomistic insight into the roles that key residues play in determining the electrostatic environment and hydrogen-bonding interactions experienced by the nitrile probe. For the M116C-CN probe, equilinen binding reorients an active-site water molecule that is directly hydrogen-bonded to the nitrile probe, resulting in a more linear CN‑‑H angle and increasing the CN frequency upon binding. For the F86C-CN probe, equilinen binding orients the Asp103 residue, decreasing the hydrogen-bonding distance between the Asp103 backbone and the nitrile probe and slightly increasing the CN frequency. This QM/MM methodology is applicable to a wide range of biological systems and has the potential to assist in the elucidation of the fundamental principles underlying enzyme catalysis