Proton Transfer Events Research Articles

Classical Models of Hydroxide for Proton Hopping Simulations.

Hydronium (H3O+) and hydroxide (OH-) ions perform structural diffusion in water via sequential proton transfers ("Grotthuss hopping"). This phenomenon can be accounted for by interspersing stochastic proton transfer events in classical molecular dynamics simulations. The implementation of OH--mediated proton hopping is particularly challenging because classical force fields are known to produce overcoordinated solvation structures around the OH- ion. Here, we first explore the ability of two-particle point-charge models to reproduce both the solvation free energy and coordination number in TIP3P water. We find that this is possible only with unphysical changes in the nonbonded parameters which create problems in proton hopping simulations. We then construct a classical OH- model with the charge of oxygen distributed among three auxiliary particles. This model favors a lower coordination number by accepting three hydrogen bonds and weakly donating one. The model was implemented in the MOBHY module of the CHARMM program and was fit to reproduce the experimental aqueous diffusion coefficient of OH-. This parameterization gave reasonable electrophoretic mobilities and the expected accelerated transport under nanoconfinement.

Exploring the catalytic mechanism of the 10-23 DNAzyme: insights from pH-rate profiles.

The 10-23 DNAzyme, a catalytic DNA molecule with RNA-cleaving activity, has garnered significant interest for its potential therapeutic applications as a gene-silencing agent. However, the lack of a detailed understanding about its mechanism has hampered progress. A recent structural analysis has revealed a highly organized conformation thanks to the stabilization of specific interactions within the catalytic core of the 10-23 DNAzyme, which facilitate the cleavage of RNA. In this configuration, it has been shown that G14 is in good proximity to the cleavage site which suggests its role as a general base, by activating the 2'-OH nucleophile, in the catalysis of the 10-23 DNAzyme. Also, the possibility of a hydrated metal acting as a general acid has been proposed. In this study, through activity assays, we offer evidence of the involvement of general acid-base catalysis in the mechanism of the 10-23 DNAzyme by analyzing its pH-rate profiles and the role of G14, and metal cofactors like Mg2+ and Pb2+. By substituting G14 with its analogue 2-aminopurine and examining the resultant pH-rate profiles, we propose the participation of G14 in a catalytically relevant proton transfer event, acting as a general base. Further analysis, using Pb2+ as a cofactor, suggests the capability of the hydrated metal ion to act as a general acid. These functional results provide critical insights into the catalytic strategies of RNA-cleaving DNAzymes, revealing common mechanisms among nucleic acid enzymes that cleave RNA.

Proton Transport in Aqueous Phosphoric, Sulfuric, and Nitric Acids: An Ab Initio Study

Proton transport plays a pivotal role in various electrochemical processes and technologies. It occurs through two primary mechanisms: the vehicular mechanism where a protonic defect moves with the aid of a molecular entity; and the ‘Grotthuss mechanism’ where a proton diffuses by being transferred between host molecules via hydrogen bonds. Recently, results from ab initio molecular dynamics (AIMD) simulations combined with dielectric spectroscopy, light, and quasielastic neutron scattering revealed that protons in neat phosphoric acid indeed move by surprisingly short jumps (~0.5-0.7 Å)1,2. In the present work, we continue to delve into the solvation and transport of protons in aqueous acid using AIMD simulations.Aqueous systems of phosphoric acid (PA), sulfuric acid (SA), and nitric acid (NA) were examined at two different ratios of acid to water 1:1 and 1:3 to understand the similarities and differences in proton transport mechanisms in these aqueous acids. The solvation structure of H3O+ in these acid solutions resembles that in the slightly acidic water but varies in the strength of hydrogen bonds formed with the acid molecules. Our results demonstrate that the strong hydrogen bonds between the PA molecules are slightly influenced by the presence of water molecules. Furthermore, the simulations reveal that H3O+ diffuses significantly faster in the aqueous PA systems than in the solutions of either SA or NA due to the assistance of PA molecules. Proton transfer events in the process of H3O+ transport show that the acid molecule can accept a proton from H3O+, either enhancing the H3O+ diffusion by shuttling a proton through a collective proton hopping or impeding it via rattling. The shuttling event significantly contributes to the H3O+ diffusion in aqueous PA, rarely occurring in the aqueous SA and never in the aqueous NA. Moreover, decomposition of H3O+ diffusion into vehicular and structural diffusion components indicates that the higher diffusion in aqueous PA is primarily due to the structural mechanism aided by the PA molecules. In the aqueous NA systems, however, the vehicular diffusion is dominant at low water contents, while increasing water content enhances the structural diffusion via connected hydrogen bonds between the water molecules. These findings shed light on the role of acid molecules in proton transport within their aqueous solutions, advancing our understanding of these fundamental mechanisms.

Roles of H-Bonding and Hydride Solvation in the Reaction of Hydrated (Di)electrons with Water to Create H2 and OH.

Even though single hydrated electrons (ehyd-'s) are stable in liquid water, two hydrated electrons can bimolecularly react with water to create H2 and hydroxide: ehyd- + ehyd- + 2H2O → H2 + 2OH-. The rate of this reaction has an unusual temperature and isotope dependence as well as no dependence on ionic strength, which suggests that cosolvation of two electrons as a single hydrated dielectron (e2,hyd2-) might be an important intermediate in the mechanism of this reaction. Here, we present an ab initio density functional theory study of this reaction to better understand the potential properties, reactivity, and experimental accessibility of hydrated dielectrons. Our simulations create hydrated dielectrons by first simulating single ehyd-'s and then injecting a second electron, providing a well-defined time zero for e2,hyd2- formation and offering insight into a potential experimental route to creating dielectrons and optically inducing the reaction. We find that e2,hyd2- immediately forms in every member of our ensemble of trajectories, allowing us to study the molecular mechanism of H2 and OH- formation. The subsequent reaction involves separate proton transfer steps with a generally well-defined hydride subintermediate. The time scales for both proton transfer steps are quite broad, with the first proton transfer step spanning times over a few ps, while the second proton transfer step varies over ∼150 fs. We find that the first proton transfer rate is dictated by whether or not the reacting water is part of an H-bond chain that allows the newly created OH- to rapidly move by Grotthuss-type proton hopping to minimize electrostatic repulsion with H-. The second proton transfer step depends significantly on the degree of solvation of H-, leading to a wide range of reactive geometries where the two waters involved can lie either across the dielectron cavity or more adjacent to each other. This also allows the two proton transfer events to take place either effectively concertedly or sequentially, explaining differing views that have been presented in the literature.

Proton Transfer via Arginine with Suppressed pKa Mediates Catalysis by Gentisate and Salicylate Dioxygenase.

Gentisate and salicylate 1,2-dioxygenases (GDO and SDO) facilitate aerobic degradation of aromatic rings by inserting both atoms of dioxygen into their substrates, thereby participating in global carbon cycling. The role of acid-base catalysts in the reaction cycles of these enzymes is debatable. We present evidence of the participation of a proton shuffler during catalysis by GDO and SDO. The pH dependence of Michaelis-Menten parameters demonstrates that a single proton transfer is mandatory for the catalysis. Measurements at variable temperatures and pHs were used to determine the standard enthalpy of ionization (ΔHion°) of 51 kJ/mol for the proton transfer event. Although the observed apparent pKa in the range of 6.0-7.0 for substrates of both enzymes is highly suggestive of a histidine residue, ΔHion° establishes an arginine residue as the likely proton source, providing phylogenetic relevance for this strictly conserved residue in the GDO family. We propose that the atypical 3-histidine ferrous binding scaffold of GDOs contributes to the suppression of arginine pKa and provides support for this argument by employing a 2-histidine-1-carboxylate variant of the enzyme that exhibits elevated pKa. A reaction mechanism considering the role of the proton source in stabilizing key reaction intermediates is proposed.

Confinement Effects on Proton Transfer in TiO2 Nanopores from Machine Learning Potential Molecular Dynamics Simulations.

Improved understanding of proton transfer in nanopores is critical for a wide range of emerging applications, yet experimentally probing mechanisms and energetics of this process remains a significant challenge. To help reveal details of this process, we developed and applied a machine learning potential derived from first-principles calculations to examine water reactivity and proton transfer in TiO2 slit-pores. We find that confinement of water within pores smaller than 0.5 nm imposes strong and complex effects on water reactivity and proton transfer. Although the proton transfer mechanism is similar to that at a TiO2 interface with bulk water, confinement reduces the activation energy of this process, leading to more frequent proton transfer events. This enhanced proton transfer stems from the contraction of oxygen-oxygen distances dictated by the interplay between confinement and hydrophilic interactions. Our simulations also highlight the importance of the surface topology, where faster proton transport is found in the direction where a unique arrangement of surface oxygens enables the formation of an ordered water chain. In a broader context, our study demonstrates that proton transfer in hydrophilic nanopores can be enhanced by controlling pore size, surface chemistry, and topology.

Exploring the interdependence of calcium and chloride activation of O2 evolution in photosystem II

Calcium and chloride are activators of oxygen evolution in photosystem II (PSII), the light-absorbing water oxidase of higher plants, algae, and cyanobacteria. Calcium is an essential part of the catalytic Mn4CaO5 cluster that carries out water oxidation and chloride has two nearby binding sites, one of which is associated with a major water channel. The co-activation of oxygen evolution by the two ions is examined in higher plant PSII lacking the extrinsic PsbP and PsbQ subunits using a bisubstrate enzyme kinetics approach. Analysis of three different preparations at pH 6.3 indicates that the Michaelis constant, KM, for each ion is less than the dissociation constant, KS, and that the affinity of PSII for Ca2+ is about ten-fold greater than for Cl−, in agreement with previous studies. Results are consistent with a sequential binding model in which either ion can bind first and each promotes the activation by the second ion. At pH 5.5, similar results are found, except with a higher affinity for Cl− and lower affinity for Ca2+. Observation of the slow-decaying Tyr Z radical, YZ•, at 77 K and the coupled S2YZ• radical at 10 K, which are both associated with Ca2+ depletion, shows that Cl− is necessary for their observation. Given the order of electron and proton transfer events, this indicates that chloride is required to reach the S3 state preceding Ca2+ loss and possibly for stabilization of YZ• after it forms. Interdependence through hydrogen bonding is considered in the context of the water environment that intervenes between Cl− at the Cl−1 site and the Ca2+/Tyr Z region.

Updates to Protex for Simulating Proton Transfers in an Ionic Liquid.

The Python-based program Protex was initially developed for simulating proton transfers in a pure protic ionic liquid via polarizable molecular dynamics simulations. This method employs a single topology approach wherein deprotonated species retain a dummy atom, which is transformed into a real hydrogen atom during the protonation process. In this work, we extended Protex to include more intricate systems and to facilitate the simulation of the Grotthuss mechanism to enhance alignment with the empirical findings. The handling of proton transfer events within Protex was further refined for increased flexibility. In the original model, each deprotonated molecule contained a single dummy atom connected to the hydrogen acceptor atom. This model posed limitations for molecules with multiple atoms that could undergo protonation. To mitigate this issue, Protex was extended to execute a proton transfer when one of these potential atoms was within a suitable proximity for the transfer event. For the purpose of maintaining simplicity, Protex continues to utilize only a single dummy atom per deprotonated molecule. Another new feature pertains to the determination of the eligibility for a proton transfer event. A range of acceptable distances can now be defined within which the transfer probability is gradually turned off. These modifications allow for a more nuanced approach to simulating proton transfer events, offering greater accuracy and control of the modeling process.

Neural Network-Based Sum-Frequency Generation Spectra of Pure and Acidified Water Interfaces with Air.

The affinity of hydronium ions (H3O+) for the air-water interface is a crucial question in environmental chemistry. While sum-frequency generation (SFG) spectroscopy has been instrumental in indicating the preference of H3O+ for the interface, key questions persist regarding the molecular origin of the SFG spectral changes in acidified water. Here we combine nanosecond long neural network (NN) reactive simulations of pure and acidified water slabs with NN predictions of molecular dipoles and polarizabilities to calculate SFG spectra of long reactive trajectories including proton transfer events. Our simulations show that H3O+ ions cause two distinct changes in phase-resolved SFG spectra: first, a low-frequency tail due to the vibrations of H3O+ and its first hydration shell, analogous to the bulk proton continuum, and second, an enhanced hydrogen-bonded band due to the ion-induced static field polarizing molecules in deeper layers. Our calculations confirm that changes in the SFG spectra of acidic solutions are caused by hydronium ions preferentially residing at the interface.

Spurious proton transfer in hydrogen bonded dimers.

In some hydrogen bonded systems, the proton may translocate along the hydrogen bond (hb) upon geometry optimization with electronic structure methods like density functional theory (DFT). Such proton transfer (pt) events, however, may be spurious. In this work, spurious pt events are investigated in a set of hydrogen bonded dimers formed with molecules HXN, where X stands for C, Si, Ge and Sn. It is found that standard approximations to the electronic exchange and correlation (xc) functional either predict spurious pt events or too strong hbs in all the (HXN)2 dimers except the (HCN)2 one. The latter result is revealed by comparing DFT calculations against wave function methods. Such spurious pt events may be avoided by fine-tuning the percentage of exact exchange (ex) in hybrid xc-functionals. It is shown that the minimum amount of ex to avoid a spurious pt event ranged from 8% to 90%, depending on the system, basis set and xc-functional approximation used. However, these fine-tuned xc-functionals inadequately describe the hb in the (HXN)2 dimers. Moreover, it is determined that the spurious pt event originates from a wrong description of the isolated HXN molecules by xc-functionals that do not include ex or a small amount of it. Therefore, it is argued that one can determine if a pt event is spurious by analyzing the geometry and electronic structure of the isolated molecule.

The Reactivity-Enhancing Role of Water Clusters in Ammonia Aqueous Solutions.

Among the many prototypical acid-base systems, ammonia aqueous solutions hold a privileged place, owing to their omnipresence in various planets and their universal solvent character. Although the theoretical optimal water-ammonia molar ratio to form NH4+ and OH- ion pairs is 50:50, our ab initio molecular dynamics simulations show that the tendency of forming these ionic species is inversely (directly) proportional to the amount of ammonia (water) in ammonia aqueous solutions, up to a water-ammonia molar ratio of ∼75:25. Here we prove that the reactivity of these liquid mixtures is rooted in peculiar microscopic patterns emerging at the H-bonding scale, where the highly orchestrated motion of 5 solvating molecules modulates proton transfer events through local electric fields. This study demonstrates that the reaction of water with NH3 is catalyzed by a small cluster of water molecules, in which an H atom possesses a high local electric field, much like the effect observed in catalysis by water droplets [ PNAS 2023, 120, e2301206120].

Developing machine-learned potentials to simultaneously capture the dynamics of excess protons and hydroxide ions in classical and path integral simulations.

The transport of excess protons and hydroxide ions in water underlies numerous important chemical and biological processes. Accurately simulating the associated transport mechanisms ideally requires utilizing abinitio molecular dynamics simulations to model the bond breaking and formation involved in proton transfer and path-integral simulations to model the nuclear quantum effects relevant to light hydrogen atoms. These requirements result in a prohibitive computational cost, especially at the time and length scales needed to converge proton transport properties. Here, we present machine-learned potentials (MLPs) that can model both excess protons and hydroxide ions at the generalized gradient approximation and hybrid density functional theory levels of accuracy and use them to perform multiple nanoseconds of both classical and path-integral proton defect simulations at a fraction of the cost of the corresponding abinitio simulations. We show that the MLPs are able to reproduce abinitio trends and converge properties such as the diffusion coefficients of both excess protons and hydroxide ions. We use our multi-nanosecond simulations, which allow us to monitor large numbers of proton transfer events, to analyze the role of hypercoordination in the transport mechanism of the hydroxide ion and provide further evidence for the asymmetry in diffusion between excess protons and hydroxide ions.

Intramolecular proton transfer reaction dynamics using machine-learned ab initio potential energy surfaces

Hydrogen bonding interactions, which are central to various physicochemical processes, are investigated in the present study using ab initio-based machine learning potential energy surfaces. Abnormally strong intramolecular O–H⋯O hydrogen bonds, occurring in β-diketone enols of malonaldehyde and its derivatives, with substituents ranging from various electron-withdrawing to electron-donating functional groups, are studied. Machine learning force fields were constructed using a kernel-based force learning model employing ab initio molecular dynamics reference data. These models were used for molecular dynamics simulations at finite temperature, and dynamical properties were determined by computing proton transfer free-energy surfaces. The chemical systems studied here show progression toward barrier-less proton transfer events at an accuracy of correlated electronic structure methods. Markov state models of the conformational states indicate shorter intramolecular hydrogen bonds exhibiting higher proton transfer rates. We demonstrate how functional group substitution can modulate the strength of intramolecular hydrogen bonds by studying the thermodynamic and kinetic properties.

Proton-Tunneling Dynamics along Low-Barrier Hydrogen Bonds: A Full-Dimensional Instanton Study of 6-Hydroxy-2-formylfulvene.

Understanding the dynamics of proton transfer along low-barrier hydrogen bonds remains an outstanding challenge of great fundamental and practical interest, reflecting the central role of quantum effects in reactions of chemical and biological importance. Here, we combine ab initio calculations with the semiclassical ring-polymer instanton method to investigate tunneling processes on the ground electronic state of 6-hydroxy-2-formylfulvene (HFF), a prototypical neutral molecule supporting low-barrier hydrogen-bonding. The results emerging from a full-dimensional ab initio instanton analysis reveal that the tunneling path does not pass through the instantaneous transition-state geometry. Instead, the tunneling process involves a multidimensional reaction coordinate with concerted reorganization of the heavy-atom skeletal framework to substantially reduce the donor-acceptor distance and drive the ensuing intramolecular proton-transfer event. The predicted tunneling-induced splittings for HFF isotopologues are in good agreement with experimental findings, leading to percentage deviations of only 20-40%. Our full-dimensional results allow us to characterize vibrational contributions along the tunneling path, highlighting the intrinsically multidimensional nature of the attendant hydron-migration dynamics.

Mechanistic roles of metal- and ligand-protonated species in hydrogen evolution with [Cp*Rh] complexes

Protonation reactions involving organometallic complexes are ubiquitous in redox chemistry and often result in the generation of reactive metal hydrides. However, some organometallic species supported by η5-pentamethylcyclopentadienyl (Cp*) ligands have recently been shown to undergo ligand-centered protonation by direct proton transfer from acids or tautomerization of metal hydrides, resulting in the generation of complexes bearing the uncommon η4-pentamethylcyclopentadiene (Cp*H) ligand. Here, time-resolved pulse radiolysis (PR) and stopped-flow spectroscopic studies have been applied to examine the kinetics and atomistic details involved in the elementary electron- and proton-transfer steps leading to complexes ligated by Cp*H, using Cp*Rh(bpy) as a molecular model (where bpy is 2,2'-bipyridyl). Stopped-flow measurements coupled with infrared and UV-visible detection reveal that the sole product of initial protonation of Cp*Rh(bpy) is [Cp*Rh(H)(bpy)]+, an elusive hydride complex that has been spectroscopically and kinetically characterized here. Tautomerization of the hydride leads to the clean formation of [(Cp*H)Rh(bpy)]+. Variable-temperature and isotopic labeling experiments further confirm this assignment, providing experimental activation parameters and mechanistic insight into metal-mediated hydride-to-proton tautomerism. Spectroscopic monitoring of the second proton transfer event reveals that both the hydride and related Cp*H complex can be involved in further reactivity, showing that [(Cp*H)Rh] is not necessarily an off-cycle intermediate, but, instead, depending on the strength of the acid used to drive catalysis, an active participant in hydrogen evolution. Identification of the mechanistic roles of the protonated intermediates in the catalysis studied here could inform design of optimized catalytic systems supported by noninnocent cyclopentadienyl-type ligands.

Crystal structure of a pre-chemistry viral RNA-dependent RNA polymerase suggests participation of two basic residues in catalysis.

The nucleic acid polymerase-catalyzed nucleotidyl transfer reaction associated with polymerase active site closure is a key step in the nucleotide addition cycle (NAC). Two proton transfer events can occur in such a nucleotidyl transfer: deprotonation of the priming nucleotide 3'-hydroxyl nucleophile and protonation of the pyrophosphate (PPi) leaving group. In viral RNA-dependent RNA polymerases (RdRPs), whether and how active site residues participate in this two-proton transfer reaction remained to be clarified. Here we report a 2.5 Å resolution crystal structure of enterovirus 71 (EV71) RdRP in a catalytically closed pre-chemistry conformation, with a proposed proton donor candidate K360 in close contact with the NTP γ-phosphate. Enzymology data reveal that K360 mutations not only reduce RdRP catalytic efficiency but also alter pH dependency profiles in both elongation and pre-elongation synthesis modes. Interestingly, mutations at R174, an RdRP-invariant residue in motif F, had similar effects with additional impact on the Michaelis constant of NTP (KM,NTP). However, direct participation in protonation was not evident for K360 or R174. Our data suggest that both K360 and R174 participate in nucleotidyl transfer, while their possible roles in acid-base or positional catalysis are discussed in comparison with other classes of nucleic acid polymerases.

Reaction within the coulomb-cage; science in retrospect

The Coulomb-cage is defined as the space where the electrostatic interaction between two bodies is more intensive than the thermal energy (kBT). For small molecule, the Coulomb-cage is a small sphere, extending only few water molecules towards the bulk and its radius is sensitive to the ionic strength of the solution. For charged proteins or membranal structures, the Coulomb-cage can engulf large fraction of the surface and provides a preferred pathway for ion propagation along the surface. Similarly, electrostatic potential at the inner space of a channel can form preferential trajectories passage for ions. The dynamics of ions inside the Coulomb-cage of ions was formulated by the studies of proton-anion recombination of excited photoacids. In the present article, we recount the study of intra- Coulomb-cage reaction taking place on the surface of macro-molecular bodies like micelles, membranes, proteins and intra-protein cavities. The study progressed stepwise, tracing the dynamics of a proton ejected from a photo-acid molecule located at defined sites (on membrane, inter-membrane space, active site of enzyme, inside Large Pore Channels etc.). Accumulation of experimental observations encouraged us to study of the reaction mechanism by molecular dynamics simulations of ions within the Coulomb-cage of proteins surface or inside large pores. The intra-Coulomb-cage proton transfer events follows closely the fine structure of the electrostatic field inside the cage and reflects the shape of nearby dielectric boundaries, the temporal ordering of the solvent molecules and the structural fluctuations of the charged side chains. The article sums some 40 years of research, which in retrospect clarifies the intra-Coulomb-cage reaction mechanism.

Imaging Fluorescence Blinking of a Mitochondrial Localization Probe: Cellular Localization Probes Turned into Multifunctional Sensors.

Mitochondrial membranes and their microenvironments directly influence and reflect cellular metabolic states but are difficult to probe on site in live cells. Here, we demonstrate a strategy, showing how the widely used mitochondrial membrane localization fluorophore 10-nonyl acridine orange (NAO) can be transformed into a multifunctional probe of membrane microenvironments by monitoring its blinking kinetics. By transient state (TRAST) studies of NAO in small unilamellar vesicles (SUVs), together with computational simulations, we found that NAO exhibits prominent reversible singlet–triplet state transitions and can act as a light-induced Lewis acid forming a red-emissive doublet radical. The resulting blinking kinetics are highly environment-sensitive, specifically reflecting local membrane oxygen concentrations, redox conditions, membrane charge, fluidity, and lipid compositions. Here, not only cardiolipin concentration but also the cardiolipin acyl chain composition was found to strongly influence the NAO blinking kinetics. The blinking kinetics also reflect hydroxyl ion-dependent transitions to and from the fluorophore doublet radical, closely coupled to the proton-transfer events in the membranes, local pH, and two- and three-dimensional buffering properties on and above the membranes. Following the SUV studies, we show by TRAST imaging that the fluorescence blinking properties of NAO can be imaged in live cells in a spatially resolved manner. Generally, the demonstrated blinking imaging strategy can transform existing fluorophore markers into multiparametric sensors reflecting conditions of large biological relevance, which are difficult to retrieve by other means. This opens additional possibilities for fundamental membrane studies in lipid vesicles and live cells.

Serial crystallography captures dynamic control of sequential electron and proton transfer events in a flavoenzyme.

Flavin coenzymes are universally found in biological redox reactions. DNA photolyases, with their flavin chromophore (FAD), utilize blue light for DNA repair and photoreduction. The latter process involves two single-electron transfers to FAD with an intermittent protonation step to prime the enzyme active for DNA repair. Here we use time-resolved serial femtosecond X-ray crystallography to describe how light-driven electron transfers trigger subsequent nanosecond-to-microsecond entanglement between FAD and its Asn/Arg-Asp redox sensor triad. We found that this key feature within the photolyase-cryptochrome family regulates FAD re-hybridization and protonation. After first electron transfer, the FAD•- isoalloxazine ring twists strongly when the arginine closes in to stabilize the negative charge. Subsequent breakage of the arginine-aspartate salt bridge allows proton transfer from arginine to FAD•-. Our molecular videos demonstrate how the protein environment of redox cofactors organizes multiple electron/proton transfer events in an ordered fashion, which could be applicable to other redox systems such as photosynthesis.

Catalytic Mechanism of Competing Proton Transfer Events from Water and Acetic Acid by [CoII(bpbH2)Cl2] for Water Splitting Processes

We performed first principles simulations to explore the water reduction process of the cobalt complex [CoII(bpbH2)Cl2], where bpbH2 = N,N'-bis(2'-pyridine carboxamide)-1,2-benzene. We considered the sequence steps of electron reduction followed by the proton addition process to observe the hydrogen evolution process. An experimental study of the catalyst showed that the increase in the acetic acid concentration triggers catalytic current and reduction of Co(II) to Co(I), and protonation occurred, yielding a Co(III)-H intermediate. Therefore, we used water and acetic acid as the proton sources. We compare the proton transfer kinetics from both the water and acetic acid. The reduction potentials and proton transfer kinetics from water or acetic acid to the reaction center were studied in a DMF solvent through the implicit solvent model. The first proton transfer from the acetic acid is more favorable, forming a CoIII-H complex and further reducing to CoII-H. The second proton transfer from water to the CoII-H moiety requires less free energy than acetic acid and is the rate-limiting step. The nature of the reduction process is also examined through the charge analysis, which reveals that the ligand becomes softer due to the C═O groups.