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This article investigates the relaxation dynamics of the ionized 2a1 state of a water molecule within a water dimer. The study was motivated by findings from two previous pieces of research that focused on the relaxation behaviors of the inner-valence ionized water dimer. The present study discloses an observation indicating that water dimers display specific fragmentation patterns following inner-valence ionization, depending on the position of the vacancy. Vacancies were created in the 2a1 state of the proton-donating water molecule (PDWM) and proton-accepting water molecule (PAWM). Utilizing Born–Oppenheimer molecular dynamics simulations, the propagation of the 2a1 ionized state was carried out for both scenarios. The results revealed proton transfer occurred when the vacancy resided in the PDWM, accompanied by the closing of decay channels for O–H bond distance (RO–H) > 1.187 Å (matching Richter et al.'s findings). Conversely, when vacancy was on PAWM, we observed no closing of decay channels (aligning with Jahnke et al.'s findings). This difference translates to distinct fragmentation pathways. In PDWM cases, 2a1 state ionization leads to H3O+ −OH• formation. In contrast, PAWM vacancies result in decay pathways leading to H2O+–H2O+ products. [ABSTRACT FROM AUTHOR]

The iron(III) complexes [Fe(H2O)n(OH)m]3−m (n + m = 5, 6, m ≤ 3) and corresponding proton transfer reactions are studied with total energy calculations, the nudged elastic band (NEB) method, and molecular dynamics (MD) simulations using ab initio and a modification of reactive force field potentials, the ReaxFF-AQ potentials, based on the implementation according to Böhm et al. [J. Phys. Chem. C 120, 10849–10856 (2016)]. Applying ab initio potentials, the energies for the reactions [Fe(H2O)n(OH)m]3−m + H2O → [Fe(H2O)n−1(OH)m+1]2−m + H3O+ in a gaseous environment are in good agreement with comparable theoretical results. In an aqueous (aq) or alkaline environment, with the aid of NEB computations, respective minimum energy paths with energy barriers of up to 14.6 kcal/mol and a collective transfer of protons are modeled. Within MD simulations at room temperature, a permanent transfer of protons around the iron(III) ion is observed. The information gained concerning the geometrical and energetic properties of water and the [Fe(H2O)n(OH)m]3−m complexes from the ab initio computations has been used as reference data to optimize parameters for the O–H–Fe interaction within the ReaxFF-AQ approach. For the optimized ReaxFF-AQ parameter set, the statistical properties of the basic water model, such as the radial distribution functions and the proton hopping functions, are evaluated. For the [Fe(H2O)n(OH)m]3−m complexes, it was found that while geometrical and energetic properties are in good agreement with the ab initio data for gaseous environment, the statistical properties as obtained from the MD simulations are only partly in accordance with the ab initio results for the iron(III) complexes in aqueous or alkaline environments. [ABSTRACT FROM AUTHOR]

The pH-dependent change in protonation of ionizable lipids is crucial for the success of lipid-based nanoparticles as mRNA delivery systems. Despite their widespread application in vaccines, the structural changes upon acidification are not well understood. Molecular dynamics simulations support structure prediction but require an a priori knowledge of the lipid packing and protonation degree. The presetting of the protonation degree is a challenging task in the case of ionizable lipids since it depends on pH and on the local lipid environment and often lacks experimental validation. Here, we introduce a methodology of combining all-atom molecular dynamics simulations with experimental total-reflection x-ray fluorescence and scattering measurements for the ionizable lipid Dlin-MC3-DMA (MC3) in POPC monolayers. This joint approach allows us to simultaneously determine the lipid packing and the protonation degree of MC3. The consistent parameterization is expected to be useful for further predictive modeling of the action of MC3-based lipid nanoparticles. [ABSTRACT FROM AUTHOR]

Interfacial processes involving metal (oxyhydr)oxide phases are important for the mobility and bioavailability of nutrients and contaminants in soils, sediments, and water. Consequently, these processes influence ecosystem health and functioning, and have shaped the biological and environmental co-evolution of Earth over geologic time. Here we employ reactive molecular dynamics simulations, supported by synchrotron X-ray spectroscopy to study the molecular-scale interfacial processes that influence surface complexation in ferrihydrite-water systems containing aqueous MoO 4 2 - . We validate the utility of this approach by calculating surface complexation models directly from simulations. The reactive force-field captures the realistic dynamics of surface restructuring, surface charge equilibration, and the evolution of the interfacial water hydrogen bond network in response to adsorption and proton transfer. We find that upon hydration and adsorption, ferrihydrite restructures into a more disordered phase through surface charge equilibration, as revealed by simulations and high-resolution X-ray diffraction. We observed how this restructuring leads to a different interfacial hydrogen bond network compared to bulk water by monitoring water dynamics. Using umbrella sampling, we constructed the free energy landscape of aqueous MoO 4 2 - adsorption at various concentrations and the deprotonation of the ferrihydrite surface. The results demonstrate excellent agreement with the values reported by experimental surface complexation models. These findings are important as reactive molecular dynamics opens new avenues to study mineral-water interfaces, enriching and refining surface complexation models beyond their foundational assumptions. [ABSTRACT FROM AUTHOR]

Near-neutral HCO3– aqueous solution plays an essential role in respiratory, mineralization and catalysis, yet the interconversion between hydrated CO2, HCO3– and CO32– and the associated proton transfer under such proton-deficient conditions remain uncovered. Here we reveal that cation enables HCO3– to self-dissociate into OH– and CO2 through a pH-independent process, where CO2 hydration and subsequent proton transfer in acid-base reactions lead to the overall exchange of oxygen isotopes between HCO3– and H2O tracked by oxygen isotope-labeled Raman spectroscopy. Isolating HCO3– from cations with crown ether impedes HCO3– dissociation and the following reactions. Further molecular dynamics simulations demonstrate that the interplay between HCO3– and hydrated cations drives HCO3– dissociation. This study suggests a natural proton channel upon coupling HCO3– with cations. Unlike the traditional views that HCO3- anions transit to either CO2 or CO32- upon suffering pH changes. Here, the authors report that cation enables HCO3- to self-dissociate into OH- and CO2 through a pH independent process, leading to the formation of acid-base encounter pairs for proton transfer. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Molecular ferroelastics with the natural features of mechanical flexibility and switchable spontaneous strain have attracted widespread attention in the scientific community due to their potential applications in tunable gratings, flexible memorizers, strain sensors, and intelligent actuators. However, most designs of molecular ferroelastics remain in the stage of blind exploration, posing a challenge to achieve a functional ferroelastic more effectively. Herein, we have successfully obtained a molecular ferroelastic, [Me2NH(CH2)2NH3](ReO4)2 (Me2NH(CH2)2NH3 = N,N‐dimethylethylenediammonium), under the guidance of the mono‐/double‐protonation strategy. The double‐protonated [Me2NH(CH2)2NH3](ReO4)2 undergoes a paraelastic‐ferroelastic phase transition with the Aizu notation of 2/mF1¯ at 322 K. Meanwhile, the theoretical calculation and experimental measurement simultaneously show that [Me2NH(CH2)2NH3](ReO4)2 possesses good mechanical flexibility, because its elastic modulus (E) of 8.26 GPa and hardness (H) of 0.45 GPa are smaller than the average values of organic crystals (E of 12.05 GPa and H of 0.5 GPa), which makes it promising to apply in wearable pressure sensors, implantable medical sensors, high‐precision tuners, etc. This work further enriches the molecular ferroelastic family and demonstrates that mono‐/double‐protonation is one of the effective molecular modification strategies for designing ferroelastics. [ABSTRACT FROM AUTHOR]

Ethylenediaminetetraacetic acid (EDTA), which has two amine and four carboxylate protonation sites, forms stable complexes with lanthanide ions. This work analyzes the coordination structure, in atomic resolution, of the Eu3+ ion complexed with EDTA in all its protonation states in aqueous solution. Eu‐EDTA complexes were modeled using classical molecular dynamics (MD) simulations using force field parameters optimized with ab initio molecular dynamics (AIMD) simulations. Structures from the MD simulations were used to predict extended X‐ray absorption fine structure (EXAFS) spectra and compared with EXAFS measurements of the Eu3+ aqua ion and Eu‐EDTA complexes at pH 3 and 11. This work details how Eu‐EDTA complex coordination structures change with increasing protonation of the EDTA ligand in the complex, from the tightly bound unprotonated complex to the unbinding of the fully protonated EDTA ligand from the Eu3+ ion as both become solvated by water. Agreement between predicted and measured EXAFS spectra supports the findings from simulation. [ABSTRACT FROM AUTHOR]

Glyphosate is a widely used herbicide, and its protonation and deprotonation sites are fundamental to understanding its properties. In this work, the sodiated, protonated, and deprotonated glyphosate were evaluated in the gas phase by infrared multiple photon dissociation spectroscopy to determine the exact nature of these coordination, protonation, and deprotonation states in the gas phase. In this context, Natural Bond Orbital analyses were carried out to unravel interactions that govern glyphosate (de)protonation states in the gas phase. The solvent effect on the protonation/deprotonation equilibria was also investigated by implicit (Solvation Model Based on Density and polarizable continuum models) and explicit solvation models (Monte Carlo and Molecular Dynamics simulations). These results show that glyphosate is protonated in the phosphonate group in the gas phase because of the strong hydrogen bond between the carboxylic oxygen (O7) and the protonated phosphonate group (O8–H19), while the most stable species in water is protonated at the amino group because of the preferential interaction of the NH2+ group and the solvent water molecules. Similarly, deprotonated glyphosate [Glyp−H]− was shown to be deprotonated at the phosphonate group in the gas phase but not in solution, also because of the preferential solvation of the NH2+ group present in the other deprotomers. Therefore, these results show that the stabilization of the protonated amino group by the solvent molecules is the governing factor of the (de)protonation equilibrium of glyphosate in water. [ABSTRACT FROM AUTHOR]

The TWIK-related acid-sensitive K+ channel 3 (TASK3) belongs to the two-pore domain (K2P) potassium channel family, which regulates cell excitability by mediating a constitutive "leak" potassium efflux in the nervous system. Extracellular acidification inhibits TASK3 channel, but the molecular mechanism by which channel inactivation is coupled to pH decrease remains unclear. Here, we report the cryo-electron microscopy structures of human TASK3 at neutral and acidic pH. Structural comparison revealed selectivity filter (SF) rearrangements upon acidification, characteristic of C-type inactivation, but with a unique structural basis. The extracellular mouth of the SF was prominently dilated and simultaneously blocked by a hydrophobic gate. His98 protonation shifted the conformational equilibrium between the conductive and C-type inactivated SF toward the latter by engaging a cation-p interaction with Trp78, consistent with molecular dynamics simulations and electrophysiological experiments. Our work illustrated how TASK3 is gated in response to extracellular pH change and implies how physiological stimuli might directly modulate the C-type gating of K2P channels. [ABSTRACT FROM AUTHOR]

Despite its simple molecular formula, obtaining an accurate in silico description of water is far from straightforward. Many of its very peculiar properties are quite elusive, and in particular, obtaining good estimations of the diffusion coefficients of the solvated proton and hydroxide at a reasonable computational cost has been an unsolved challenge until now. Here, I present extensive results of several unusually long ab initio molecular dynamics (MD) simulations employing different combinations of the Born–Oppenheimer and second-generation Car–Parrinello MD propagation methods with different ensembles (NVE and NVT) and thermostats, which show that these methods together with the RPBE-D3 functional provide a very accurate estimation of the diffusion coefficients of the solvated H3O+ and OH− ions, together with an extremely accurate description of several properties of neutral water (such as the structure of the liquid and its diffusion and shear viscosity coefficients). In addition, I show that the estimations of D H 3 O + and D OH − depend dramatically on the simulation length, being necessary to reach timescales in the order of hundreds of picoseconds to obtain reliable results. [ABSTRACT FROM AUTHOR]

Nanoparticles can serve as an efficient reaction environment for bimolecular reactions as the reactants concentrate either inside the nanoparticle or on the surface of the nanoparticle. The reaction rate is then controlled by the rate of formation of the reaction pairs. We demonstrate this concept on the example of electron-induced reactions in hydrogen peroxide. We consider two types of nanoparticle environments: solid argon particles, only weakly interacting with the hydrogen peroxide reactant, and ice particles with a much stronger interaction. The formation of hydrogen peroxide dimers is investigated via classical molecular dynamics (MD) simulations on a microsecond timescale. With a modified force field for hydrogen peroxide, we found out a fast formation and stabilization of the hydrogen peroxide dimer for argon nanoparticles, while the reaction pair was formed reversibly at a much slower rate on the water nanoparticles. We have further investigated the electron-induced reactions using non-adiabatic ab initio MD simulations, identifying the possible reaction products upon the ionization or electron attachment. The major reaction path in all cases corresponded to a proton transfer. The computational findings are supported by mass spectrometry experiments, where large ArM and (H2O)M nanoparticles are generated, and several hydrogen peroxide molecules are embedded on these nanoparticles in a pickup process. Subsequently, the nanoparticles are ionized either positively by 70 eV electrons or negatively by electron attachment at electron energies below 5 eV. The recorded mass spectra demonstrate the efficient coagulation of H2O2 on ArM, while it is quite limited on (H2O)M. [ABSTRACT FROM AUTHOR]

Heterostructures of 2D materials offer a fertile ground to study ion transport and charge storage. Here, we use ab initio molecular dynamics to examine the proton-transfer/diffusion and redox behavior in a water layer confined in the graphene-Ti3C2O2 heterostructure. We find that in comparison with the similar interface of water confined between Ti3C2O2 layers, the proton redox rate in the dissimilar interface of graphene-Ti3C2O2 is much higher, owing to the very different interfacial structure as well as the interfacial electric field induced by an electron transfer in the latter. Water molecules in the dissimilar interface of the graphene-Ti3C2O2 heterostructure form a denser hydrogen-bond network with a preferred orientation of water molecules, leading to an increase in proton mobility with proton concentration in the graphene-Ti3C2O2 interface. As the proton concentration further increases, proton mobility decreases due to increasingly more frequent surface redox events that slow down proton mobility due to binding with surface O atoms. Our work provides important insights into how the dissimilar interface and their associated interfacial structure and properties impact proton transfer and redox in the confined space. [ABSTRACT FROM AUTHOR]

This study employs first principles and classical molecular dynamics approach to investigate distinct proton landscape and scattering events among aristotype and hettotype BaCeO 3 polymorph. We systematically sampled different migration pathways to examine the thermionic behaviour and lattice disorder against the activation energy profile as a function of operating temperatures. According to DFT outcomes, the asymmetric landscape among hettotype structures entails a feeble vacancy formation energy (E vac = 0.326 eV and 0.485 eV) with noticeable lattice strain (ε = 0.258 % and 0.167 %) and desirable proton transfer pathway relative to aristotype counterpart. The transport characteristics from molecular dynamics on the other hand reveals an accelerated proton transfer at intermediate temperatures (300–550 °C) due to symmetric hydrogen bonding around the proton neighbourhood with a curtailed translational barrier from the low frequency lattice phonons. However, repellent response at elevated temperatures (>550 °C) illustrates the advent of ambipolar characteristics (H+/O2−), structural phase transitions, defect scattering events and the rise of artificial barrier as localized proton traps via proton polaron and defect (V O.. ) interactions. The study as a result accentuates the demand of structural and dynamical coherence to extend the commercial utility of BaCeO 3 polymorph for the fuel cell technology. • Desirable proton landscape among hettotype structures favour rapid proton transport between (300–550 °C). • Low frequency lattice phonon curtails the local energy barrier for unimpeded proton migration below 550 °C. • Cationic disorder, ambipolar response and defect scattering events strengthens electrophysical fluctuations beyond 550 °C. • Very strong proton-polaron coupling beyond 600 °C trap protons due to localized artificial barrier and charge redistribution. [ABSTRACT FROM AUTHOR]

Deposition of platinum ions in the proton exchange membrane significantly affects the long-term stability and proton transport capacity of the membrane electrode assembly. In this study, the impacts of deposited Pt particles on the intrinsic properties of proton exchange membranes and its mechanisms are investigated using molecular dynamics simulation method. The effect of differently sized Pt particles on water channel connectivity and proton conductivity in proton exchange membranes under dry, normal, and saturated conditions was detailly discussed. The results reveal that Pt particles reduce water channel connectivity at low hydration level while increasing it at normal and high hydration levels. However, the enhancement mechanism is different. Moreover, proton conductivity was evaluated by examining the diffusion of hydronium ions and hydrogen bond dynamics. We found that the proton conduction performance of the membranes at low hydration levels is significantly reduced by Pt particles. We believe this study can promote the design of more robust and efficient proton exchange membranes. • The effect of Pt particles on water channel connectivity varies with hydration level. • Pt particles larger than 2 nm significantly improve the water channel connectivity. • The mechanisms by which Pt affects watershed structure differ at 3 hydration levels. • The proton conductivity at low hydration levels is reduced by Pt particles. • The inhibitory effect of Pt on the hopping mechanism increases with particle size. [ABSTRACT FROM AUTHOR]

Proton exchange membrane (PEM) is a key component of proton exchange membrane fuel cell, and its proton conductivity directly affects the performance of fuel cell. Imparting order to Nafion molecules is one of potential effective approaches that can significantly improve the proton transport performance of PEM, but the underlying mechanism of this effect as well as the regulatory mechanism is unknown. In order to investigate the regulatory mechanism of temperature, electric field, and water content on the transport mechanism of the PEM and compare the transport properties between ordered and amorphous membranes, this study examined the proton migration rate of ordered and amorphous membranes under different electric field and water contents at 300 K and 350 K with molecular dynamics methods. The simulation results indicate that the ordered PEM exhibits better proton conductivity compared with the amorphous PEM due to its ordered structure with smoothly connected proton transport channels. The proton conductivity of the ordered PEM with a water content of 16 exhibits a remarkably high proton conductivity of 0.153 S/cm at a temperature of 350 K. Additionally, it was found that increasing electric field intensity, temperature, and hydration level can enhance the diffusion of water molecules and hydrated protons and improve the proton conductivity of the PEM. Especially, at low electric field intensity, ordered PEM demonstrates superior proton conductivity compared to amorphous PEM. However, as the electric field strength increases to 0.7 V/nm, the proton diffusion behaviour of amorphous PEM gradually surpasses that of ordered PEM. Moreover, the electric field can enhance the anisotropic diffusion behaviour of PEM. As the electric field increases from 0 V/nm to 0.7 V/nm, the diffusion coefficient parallel to the direction of the electric field increases by three orders of magnitude, while the diffusion coefficient perpendicular to the direction of the electric field increases by only one order of magnitude. • Different water content systems of amorphous and ordered PEM were constructed and studied by using molecular dynamics. • The diffusion coefficient and proton conductivity of the amorphous and ordered PEM were calculated. • Increasing the order degree of Nafion molecular chain increases the proton conductivity of the proton exchange membrane. • Increasing the electric field strength, temperature and hydration level can improve the proton conductivity of the PEM. • Ordered PEM exhibits better proton conductivity than amorphous PEM at low electric field strengths. [ABSTRACT FROM AUTHOR]

After drawing comparisons between the reaction pathways of cytochrome c oxidase (CcO, Complex 4) and the preceding complex cytochrome bci (Complex 3), both being proton pumping complexes along the electron transport chain, we provide an analysis of the reaction pathways in bacterial ba3 class CcO, comparing spectroscopic results and kinetics observations with results from DFT calculations. For an important arc of the catalytic cycle in CcO, we can trace the energy pathways for the chemical protons and show how these pathways drive proton pumping of the vectorial protons. We then explore the proton loading network above the Fe heme a3-CuB catalytic center, showing how protons are loaded in and then released by combining DFT-based reaction energies with molecular dynamics simulations over states of that cycle. We also propose some additional reaction pathways for the chemical and vector protons based on our recent work with spectroscopic support. [ABSTRACT FROM AUTHOR]

The gastric proton pump (H+,K+-ATPase) transports a proton into the stomach lumen for every K+ ion exchanged in the opposite direction. In the lumen-facing state of the pump (E2), the pump selectively binds K+ despite the presence of a 10-fold higher concentration of Na+. The molecular basis for the ion selectivity of the pump is unknown. Using molecular dynamics simulations, free energy calculations, and Na+ and K+-dependent ATPase activity assays, we demonstrate that the K+ selectivity of the pump depends upon the simultaneous protonation of the acidic residues E343 and E795 in the ion-binding site. We also show that when E936 is protonated, the pump becomes Na+ sensitive. The protonation-mimetic mutant E936Q exhibits weak Na+-activated ATPase activity. A 2.5-Å resolution cryo-EM structure of the E936Q mutant in the K+-occluded E2-Pi form shows, however, no significant structural difference compared with wildtype except less-than-ideal coordination of K+ in the mutant. The selectivity toward a specific ion correlates with a more rigid and less fluctuating ion-binding site. Despite being exposed to a pH of 1, the fundamental principle driving the K+ ion selectivity of H+,K+-ATPase is similar to that of Na+,K+-ATPase: the ionization states of the acidic residues in the ion-binding sites determine ion selectivity. Unlike the Na+,K+-ATPase, however, protonation of an ion-binding glutamate residue (E936) confers Na+ sensitivity. [ABSTRACT FROM AUTHOR]

Glutathione (GSH) is a common antioxidant and its biological activity depends on the conformation and protonation state. We used molecular dynamics, Raman and Raman optical activity (ROA) spectroscopies to investigate GSH structural changes in a broad pH range. Factor analysis of the spectra provided protonation constants (2.05, 3.45, 8.62, 9.41) in good agreement with previously published values. Following the analysis, spectra of differently protonated forms were obtained by extrapolation. The complete deprotonation of the thiol group above pH 11 was clearly visible in the spectra; however, many spectral features did not change much with pH. Experimental spectra at various pH values were decomposed into the simulated ones, which allowed us to study the conformer populations and quality of molecular dynamics (MD). According to this combined ROA/MD analysis conformation of the GSH backbone is affected by the pH changes only in a limited way. The combination of ROA with the computations thus has the potential to improve the MD force field and obtain more accurate populations of the conformer species. The methodology can be used for any molecule, but for a more detailed insight better computational techniques are needed in the future. [ABSTRACT FROM AUTHOR]

YiiP from Shewanella oneidensis is a prokaryotic Zn2+/H+ antiporter that serves as a model for the Cation Diffusion Facilitator (CDF) superfamily, members of which are generally responsible for homeostasis of transition metal ions. Previous studies of YiiP as well as related CDF transporters have established a homodimeric architecture and the presence of three distinct Zn2+ binding sites named A, B, and C. In this study, we use cryo-EM, microscale thermophoresis and molecular dynamics simulations to address the structural and functional roles of individual sites as well as the interplay between Zn2+ binding and protonation. Structural studies indicate that site C in the cytoplasmic domain is primarily responsible for stabilizing the dimer and that site B at the cytoplasmic membrane surface controls the structural transition from an inward facing conformation to an occluded conformation. Binding data show that intramembrane site A, which is directly responsible for transport, has a dramatic pH dependence consistent with coupling to the proton motive force. A comprehensive thermodynamic model encompassing Zn2+ binding and protonation states of individual residues indicates a transport stoichiometry of 1 Zn2+ to 2-3 H+ depending on the external pH. This stoichiometry would be favorable in a physiological context, allowing the cell to use the proton gradient as well as the membrane potential to drive the export of Zn2+. [ABSTRACT FROM AUTHOR]

The presence of carboxyl groups in a molecule delivers an affinity to metal cations and a sensitivity to the chemical environment, especially for an environment that can give rise to intermolecular hydrogen bonds. Carboxylate groups can also induce intramolecular interactions, such as the formation of hydrogen bonds with donor groups, leading to an impact on the conformational space of biomolecules. In the latter case, the protonation state of the amino groups plays an important role. In order to provide an accurate description of the modifications induced in a carboxylated molecule by the formation of hydrogen bonds, one needs a compromise between a quantum chemical description of the system and the necessity to take into account explicit solvent molecules. In this work, we propose a bottom‐up approach to study the conformational space and the carboxylate stretching band of (bio)organic anions. Starting from the anions in a continuum solvent, we then move to calculations using a microsolvation approach including one explicit water molecule per polar group, immersed in a continuum. Finally, we run QM/MM molecular dynamics simulations to analyze the solvation properties and to explore the anions conformational space. The results thus obtained are in good agreement with the description given by the microsolvation approach and they bring a more detailed description of the solvation shell and of the intermolecular hydrogen bonds. [ABSTRACT FROM AUTHOR]

In this work, a series of analyses are performed on ab initio molecular dynamics simulations of a hydrated excess proton in water to quantify the relative occurrence of concerted hopping events and "rattling" events and thus to further elucidate the hopping mechanism of proton transport in water. Contrary to results reported in certain earlier papers, the new analysis finds that concerted hopping events do occur in all simulations but that the majority of events are the product of proton rattling, where the excess proton will rattle between two or more waters. The results are consistent with the proposed "special-pair dance" model of the hydrated excess proton wherein the acceptor water molecule for the proton transfer will quickly change (resonate between three equivalent special pairs) until a decisive proton hop occurs. To remove the misleading effect of simple rattling, a filter was applied to the trajectory such that hopping events that were followed by back hops to the original water are not counted. A steep reduction in the number of multiple hopping events is found when the filter is applied, suggesting that many multiple hopping events that occur in the unfiltered trajectory are largely the product of rattling, contrary to prior suggestions. Comparing the continuous correlation function of the filtered and unfiltered trajectories, we find agreement with experimental values for the proton hopping time and Eigen–Zundel interconversion time, respectively. [ABSTRACT FROM AUTHOR]

Liquid state theories have emerged as a numerically efficient alternative to costly molecular dynamics simulations of electron transfer reactions in solution. In a recent paper [Jeanmairet et al., Chem. Sci. 10, 2130–2143 (2019)], we introduced the framework to compute the energy gap, free energy profile, and reorganization free energy using molecular density functional theory. However, this technique, as other molecular liquid state theories, overestimates the bulk pressure of the fluid. Because of the very high pressure, the predicted free energy is dramatically exaggerated. Several attempts were made to fix this issue, either based on simple a posteriori correction or by introducing bridge terms. By studying two model half reactions in water, Cl → Cl+ and Cl → Cl−, we assess the correctness of these two types of corrections to study electron transfer reactions. We found that a posteriori correction, because it violates the Variational principle, leads to an inconsistency in the definition of the reorganization free energy and should not be used to study electron transfer reactions. The bridge approach, because it is theoretically well grounded, is perfectly suitable for this type of systems. [ABSTRACT FROM AUTHOR]

Computational protein design relies on simulations of a protein structure, where selected amino acids can mutate randomly, and mutations are selected to enhance a target property, such as stability. Often, the protein backbone is held fixed and its degrees of freedom are modeled implicitly to reduce the complexity of the conformational space. We present a hybrid method where short molecular dynamics (MD) segments are used to explore conformations and alternate with Monte Carlo (MC) moves that apply mutations to side chains. The backbone is fully flexible during MD. As a test, we computed side chain acid/base constants or pKa's in five proteins. This problem can be considered a special case of protein design, with protonation/deprotonation playing the role of mutations. The solvent was modeled as a dielectric continuum. Due to cost, in each protein we allowed just one side chain position to change its protonation state and the other position to change its type or mutate. The pKa's were computed with a standard method that scans a range of pH values and with a new method that uses adaptive landscape flattening (ALF) to sample all protonation states in a single simulation. The hybrid method gave notably better accuracy than standard, fixed-backbone MC. ALF decreased the computational cost a factor of 13. [ABSTRACT FROM AUTHOR]

We explicitly compute the non-equilibrium molecular dynamics of protons in the solid acid CsH2PO4 on the micrometer length scale via a multiscale Markov model: The molecular dynamics/matrix propagation (MDM) method. Within the MDM approach, the proton dynamics information of an entire molecular dynamics simulation can be condensed into a single M × M matrix (M is the number of oxygen atoms in the simulated system). Due to this drastic reduction in the complexity, we demonstrate how to increase the length and time scales in order to enable the simulation of inhomogeneities of CsH2PO4 systems at the nanometer scale. We incorporate explicit correlation of protonation dynamics with the protonation state of the neighboring proton sites and illustrate that this modification conserves the Markov character of the MDM method. We show that atomistic features such as the mean square displacement and the diffusion coefficient of the protons can be computed quantitatively from the matrix representation. Furthermore, we demonstrate the application potential of the scheme by computing the explicit dynamics of a non-equilibrium process in an 8 μm CsH2PO4 system during 5 ms. [ABSTRACT FROM AUTHOR]

We derive a matrix formalism for the simulation of long range proton dynamics for extended systems and timescales. On the basis of an ab initio molecular dynamics simulation, we construct a Markov chain, which allows us to store the entire proton dynamics in an M × M transition matrix (where M is the number of oxygen atoms). In this article, we start from common topology features of the hydrogen bond network of good proton conductors and utilize them as constituent constraints of our dynamic model. We present a thorough mathematical derivation of our approach and verify its uniqueness and correct asymptotic behavior. We propagate the proton distribution by means of transition matrices, which contain kinetic data from both ultra-short (sub-ps) and intermediate (ps) timescales. This concept allows us to keep the most relevant features from the microscopic level while effectively reaching larger time and length scales. We demonstrate the applicability of the transition matrices for the description of proton conduction trends in proton exchange membrane materials. [ABSTRACT FROM AUTHOR]

Here, we present a parametrization of the metadynamics simulations for reactions involving breaking the chemical bonds along a single collective variable coordinate. The parameterization is based on the similarity between the bias potential in metadynamics and the quantum potential in the de Broglie–Bohm formalism. We derive the method and test it on two prototypical reaction types: proton transfer and breaking of the cyclohexene cycle (reversed Diels–Alder reaction). [ABSTRACT FROM AUTHOR]

Protonation of key histidine residues has been long implicated in the acid-mediated cellular action of the diphtheria toxin translocation (T-) domain, responsible for the delivery of the catalytic domain into the cell. Here, we use a combination of computational (constant-pH Molecular Dynamics simulations) and experimental (NMR, circular dichroism, and fluorescence spectroscopy along with the X-ray crystallography) approaches to characterize the initial stages of conformational change happening in solution in the wild-type T-domain and in the H223Q/H257Q double mutant. This replacement suppresses the acid-induced transition, resulting in the retention of a more stable protein structure in solutions at pH 5.5 and, consequently, in reduced membrane-disrupting activity. Here, for the first time, we report the pKa values of the histidine residues of the T-domain, measured by NMR-monitored pH titrations. Most peaks in the histidine side chain spectral region are titrated with pKas ranging from 6.2 to 6.8. However, the two most up-field peaks display little change down to pH 6, which is a limiting pH for this protein in solution at concentrations required for NMR. These peaks are absent in the double mutant, suggesting they belong to H223 and H257. The constant-pH simulations indicate that for the T-domain in solution, the pKa values for histidine residues range from 3.0 to 6.5, with those most difficult to protonate being H251 and H257. Taken together, our experimental and computational data demonstrate that previously suggested cooperative protonation of all six histidines in the T-domain does not occur. [ABSTRACT FROM AUTHOR]

In bacterial voltage-gated sodium channels, the passage of ions through the pore is controlled by a selectivity filter (SF) composed of four glutamate residues. The mechanism of selectivity has been the subject of intense research, with suggested mechanisms based on steric effects, and ion-triggered conformational change. Here, we propose an alternative mechanism based on ion-triggered shifts in pKa values of SF glutamates. We study the NavMs channel for which the open channel structure is available. Our free-energy calculations based on molecular dynamics simulations suggest that pKa values of the four glutamates are higher in solution of K+ ions than in solution of Na+ ions. Higher pKa in the presence of K+ stems primarily from the higher population of dunked conformations of the protonated Glu sidechain, which exhibit a higher pKa shift. Since pKa values are close to the physiological pH, this results in predominant population of the fully deprotonated state of glutamates in Na+ solution, while protonated states are predominantly populated in K+ solution. Through molecular dynamics simulations we calculate that the deprotonated state is the most conductive, the singly protonated state is less conductive, and the doubly protonated state has significantly reduced conductance. Thus, we propose that a significant component of selectivity is achieved through ion-triggered shifts in the protonation state, which favors more conductive states for Na+ ions and less conductive states for K+ ions. This mechanism also suggests a strong pH dependence of selectivity, which has been experimentally observed in structurally similar NaChBac channels. [ABSTRACT FROM AUTHOR]

Introduction: Enalapril maleate is an antihypertensive ethyl ester pro-drug with two crystalline forms. A network of hydrogen bonds in both polymorphs plays an important role on solid-state stability, charge transfer process and degradation reactions (when exposed to high humidity, temperature and/or pH changes). Computational Procedures: Supramolecular arrangement was proposed by Hirshfeld surface using the CrystalExplorer17 software and quantum theory of atoms in molecules. The electronic structure properties were calculated using the functional hybrid M06-2X with 6–311++G** base function employing diffuse and polarization functions to improve the description of hydrogen atoms on intermolecular interactions. Also, the H+ charge transfer between enalapril and maleate molecules was performed using Car-Parrinello molecular dynamics with the Verlet algorithm. In both simulations, the temperature of the ionic system was maintained around 300 K using the Nosé-Hoover thermostat and the electronic system evolved without the use of the thermostat. Results: This work evaluates the effect of maleate on the structural stability of enalapril maleate solid state. The electronic structural analysis points out a partially covalent character for N1-H∙∙∙O7 interaction; and the molecular dynamic showed a decentralized hydrogen on maleate driving a decomposition by charge transfer process while a centered hydrogen driving the stabilization. The charge transfer process and the mobility of the proton (H+) between enalapril and maleate molecules was demonstrated using supramolecular modeling analyses and molecular dynamics calculations. [ABSTRACT FROM AUTHOR]

Flaviviruses are enveloped viruses which include human pathogens that are predominantly transmitted by mosquitoes and ticks. Some, such as dengue virus, exhibit the phenomenon of antibody-dependent enhancement (ADE) of disease, making vaccine-based routes of fighting infections problematic. The pH-dependent conformational change of the envelope (E) protein required for fusion between the viral and endosomal membranes is an attractive point of inhibition by antivirals as it has the potential to diminish the effects of ADE. We examined six flaviviruses by employing large-scale molecular dynamics (MD) simulations of raft systems that represent a substantial portion of the flaviviral envelope. We utilised a benzene-mapping approach that led to a discovery of shared hotspots and conserved cryptic sites. A cryptic pocket previously shown to bind a detergent molecule exhibited strain-specific characteristics. An alternative conserved cryptic site at the E protein domain interfaces showed a consistent dynamic behaviour across flaviviruses and contained a conserved cluster of ionisable residues. Constant-pH simulations revealed cluster and domaininterface disruption under low pH conditions. Based on this, we propose a cluster-dependent mechanism that addresses inconsistencies in the histidine-switch hypothesis and highlights the role of cluster protonation in orchestrating the domain dissociation pivotal for the formation of the fusogenic trimer. [ABSTRACT FROM AUTHOR]

Despite numerous studies investigating histamine and its receptors, the impact of histamine protonation states on binding to the histamine H 1 -receptor (H 1 R) has remained elusive. Therefore, we assessed the influence of different histamine tautomers (τ -tautomer, π -tautomer) and charge states (mono- vs. dicationic) on the interaction with the ternary histamine-H 1 R-Gq complex. In atomistic molecular dynamics simulations, the τ -tautomer formed stable interactions with the receptor, while the π -tautomer induced a rotation of the histamine ring by 180° and formed only weaker hydrogen bonding interactions. This suggests that the τ -tautomer is more relevant for stabilization of the active ternary histamine-H 1 R-Gq complex. In addition to the two monocationic tautomers, the binding of dicationic histamine was investigated, whose interaction with the H 1 R had been observed in a previous experimental study. Our simulations showed that the dication is less compatible with the ternary histamine-H 1 R-Gq complex and rather induces an inactive conformation in the absence of the Gq protein. Our data thus indicate that the charge state of histamine critically affects its interactions with the H 1 R. Ultimately these findings might have implications for the future development of new ligands that stabilize distinct H 1 R activation states. [ABSTRACT FROM AUTHOR]

The transport of protons is critical in a variety of bio- and electro-chemical processes and technologies. The Grotthuss mechanism is considered to be the most efficient proton transport mechanism, generally implying a transfer of protons between 'chains' of host molecules via elementary reactions within the hydrogen bonds. Although Grotthuss proposed this concept more than 200 years ago, only indirect experimental evidence of the mechanism has been observed. Here we report the first experimental observation of proton transfer between the molecules in pure and 85% aqueous phosphoric acid. Employing dielectric spectroscopy, quasielastic neutron, and light scattering, and ab initio molecular dynamic simulations we determined that protons move by surprisingly short jumps of only ~0.5–0.7 Å, much smaller than the typical ion jump length in ionic liquids. Our analysis confirms the existence of correlations in these proton jumps. However, these correlations actually reduce the conductivity, in contrast to a desirable enhancement, as is usually assumed by a Grotthuss mechanism. Furthermore, our analysis suggests that the expected Grotthuss-like enhancement of conductivity cannot be realized in bulk liquids where ionic correlations always decrease conductivity. Although the Grotthuss mechanism of proton transfer is generally considered to be the most efficient means of proton transport, the search for experimental evidence of the mechanism has remained elusive and in certain cases confusing. Here, dielectric spectroscopy, quasieleastic neutron and light scattering, along with ab initio molecular dynamics simulations have been utilized to elucidate the mechanism of proton transfer in pure and 85% aqueous phosphoric acid. [ABSTRACT FROM AUTHOR]

The structural stability of the weakest bonded configurations of water clusters in the form of gas hydrate cavities D and T, as well as in the form of Kelvin's polyhedron, was tested using the local geometric optimization with the polarizable force field AMOEBA. A number of different barrier-free molecular rearrangements were observed. Most of the configurations changed their shapes, forming surface defects of the same type. But the main attention is paid to the concerted molecular reorientations leading to the proton shift along hydrogen bonds. A number of statements about the topology of the hydrogen-bonded network are rigorously proved. It is concluded that the structural stability of configurations and the features of structural transformations are basically determined by the arrangement of the homodromic hydrogen-bonded water rings. The stability of the configurations, which retained their original shape during local geometric optimization, was studied by the molecular dynamics method with a gradual increase in temperature. Some interesting effects were found. This is the stabilizing locking of the most polarized configurations, as well as very intense amplitude oscillations of the free OH group at the end of two-bond flips. [ABSTRACT FROM AUTHOR]

Proton transfer is crucial for electrocatalysis. Accumulating cations at electrochemical interfaces can alter the proton transfer rate and then tune electrocatalytic performance. However, the mechanism for regulating proton transfer remains ambiguous. Here, we quantify the cation effect on proton diffusion in solution by hydrogen evolution on microelectrodes, revealing the rate can be suppressed by more than 10 times. Different from the prevalent opinions that proton transport is slowed down by modified electric field, we found water structure imposes a more evident effect on kinetics. FTIR test and path integral molecular dynamics simulation indicate that proton prefers to wander within the hydration shell of cations rather than to hop rapidly along water wires. Low connectivity of water networks disrupted by cations corrupts the fast‐moving path in bulk water. This study highlights the promising way for regulating proton kinetics via a modified water structure. [ABSTRACT FROM AUTHOR]

Channelrhodopsin-2 (ChR2) has been one of the most important objects in the study of optogenetics. The retinal chromophore molecule absorbs photons and undergoes an isomerization reaction, which triggers the photocycle, resulting in a series of conformational changes. In this study, a series of intermediate structures (including D470, P500, P390-early, P390-late, and P520 states) of ChR2 in the photocycle were modeled, and molecular dynamics (MD) simulations were performed to elucidate the mechanism of ion channel opening of ChR2. The maximum absorption wavelength of these intermediates calculated by time-dependent density function theory (TD-DFT) is in general agreement with the experimental values, the distribution of water density gradually increases in the process of photocycle, and the radius of the ion channel is larger than 6 Å. All these results indicate that our structural models of the intermediates are reasonable. The evolution of protonation state of E90 during the photocycle is explained. E90 will deprotonate when the P390-early transforms into P390-late, in which the two conformations of P390-early and P390-late obtained from the simulations are consistent with the experimental descriptions. To validate the conductive P520 state, the potential mean force (PMF) of Na + ions passing through the P520 intermediate was calculated by using steered molecular dynamics (SMD) simulation combined with umbrella sampling. The result shows that the Na + ions passing through the channel with a very low energy barrier, especially in the central gate, is almost barrierless. This indicates that the channel is open in the P520 state. [ABSTRACT FROM AUTHOR]

Scale inhibitors are effective in preventing CaCO3 scaling in geothermal systems, but the scale inhibition performance and price of commercial scale inhibitors in high‐temperature and high‐salinity water are still not ideal. In this work, a novel modified carboxymethylated β‐cyclodextrin tetrameric (CAAS) scale inhibitor was synthesized using carboxymethylated β‐cyclodextrin, acrylic acid, 2‐acrylamido‐2‐methylpropanesulfonic acid (AMPS), and p‐styrenesulfonate (SSS) by free radical polymerization, and deprotonated CAAS (D‐CAAS) was prepared based on CAAS. The results of the static test showed that the CaCO3 scale inhibition efficiency of D‐CAAS reached 90.8% at 100°C and 800 mg/L Ca2+. Compared with that of previous commercial scale inhibitors, the scale inhibition efficiency of D‐CAAS was increased by 13.5%, and the price can be decreased by 26.1%. The results of SEM, XRD and molecular dynamics (MD) simulation showed that at 100°C–120°C, the deprotonation of D‐CAAS enhanced the weak interaction between D‐CAAS and CaCO3, inducing the transformation between calcite and vaterite and forming a loose scale. Deprotonation weakens the hydrogen bond between D‐CAAS and water to reduce the energy required for the binding of D‐CAAS to the surface of CaCO3. This study is expected to provide a low‐cost and high‐efficiency CaCO3 scale inhibitor for geothermal applications. [ABSTRACT FROM AUTHOR]

Molecular-level computer simulations of peptide aggregation, translocation, and protonation at and in biomembranes are impeded by the large time and length scales involved. We present a computationally efficient, coarse-grained, and solvent-free model for the interaction between lipid bilayers and peptides. The model combines an accurate description of mechanical membrane properties with a new granular representation of the dielectric mismatch between lipids and the aqueous phase. All-atom force fields can be easily mapped onto the coarse-grained model, and parameters for coarse-grained monopeptides accurately extrapolate to membrane permeation free energies for the corresponding dipeptides and tripeptides. Acid-base equilibria of titratable amino acid residues are further studied using a constant-pH ensemble, capturing protonation state changes upon membrane translocation. Important differences between histidine, lysine, and arginine are observed, which are in good agreement with experimental observations. [ABSTRACT FROM AUTHOR]

Proton hopping is a key reactive process within zeolite catalysis. However, the accurate determination of its kinetics poses major challenges both for theoreticians and experimentalists. Nuclear quantum effects (NQEs) are known to influence the structure and dynamics of protons, but their rigorous inclusion through the path integral molecular dynamics (PIMD) formalism was so far beyond reach for zeolite catalyzed processes due to the excessive computational cost of evaluating all forces and energies at the Density Functional Theory (DFT) level. Herein, we overcome this limitation by training first a reactive machine learning potential (MLP) that can reproduce with high fidelity the DFT potential energy surface of proton hopping around the first Al coordination sphere in the H-CHA zeolite. The MLP offers an immense computational speedup, enabling us to derive accurate reaction kinetics beyond standard transition state theory for the proton hopping reaction. Overall, more than 0.6 μs of simulation time was needed, which is far beyond reach of any standard DFT approach. NQEs are found to significantly impact the proton hopping kinetics up to ~473 K. Moreover, PIMD simulations with deuterium can be performed without any additional training to compute kinetic isotope effects over a broad range of temperatures. The quantum properties of hydrogen atoms in zeolite-catalyzed reactions are generally neglected due to high computational costs. Here, the authors leverage machine learning to derive accurate quantum kinetics for proton transfer reactions in heterogeneous catalysis. [ABSTRACT FROM AUTHOR]

Betanidin (Bd) is a nitrogenous metabolite with significant bioactive potential influenced by pH. Its free radical scavenging activity and deprotonation pathway are crucial to studying its physicochemical properties. Motivated by the published discrepancies about the best deprotonation routes in Bd, this work explores all possible pathways for proton extractions on that molecule, by using the direct approach method based on pKa. The complete space of exploration is supported by a linear relation with constant slope, where the pKa is written in terms of the associated deprotonated molecule energy. The deprotonation rounds 1, ..., 6 define groups of parallel linear models with constant slope. The intercepts of the models just depend on the protonated energy for each round, and then the pKa can be trivially ordered and explained by the energy. We use the direct approximation method to obtain the value of pKa. We predict all possible outcomes based on a linear model of the energy and some related verified assumptions. We also include a new measure of similarity or dissimilarity between the protonated and deprotonated molecules, via a geometric–chemical descriptor called the Riemann–Mulliken distance (RMD). The RMD considers the cartesian coordinates of the atoms, the atomic mass, and the Mulliken charges. After exploring the complete set of permutations, we show that the successive deprotonation process does not inherit the local energy minimum and that the commutativity of the paths does not hold either. The resulting clusterization of pKa can be explained by the local acid and basic groups of the BD, and the successive deprotonation can be predicted by using the chemical explained linear models, which can avoid unnecessary optimizations. Another part of the research uses our own algorithm based on shape theory to determine the protein's active site automatically, and molecular dynamics confirmed the results of the molecular docking of Bd in protonated and anionic form with the enzyme aldose reductase (AR). Also, we calculate the descriptors associated with the SET and SPLET mechanisms. [ABSTRACT FROM AUTHOR]

Guillardia theta anion channelrhodopsin 1 (GtACR1) is a widely used inhibitor of optogenetics with unique conductance mechanisms and photochemistry. However, the molecular mechanism of light-gated anion conduction is poorly understood without a crystal structure for the intermediate state. In this study, we built the dark-state model based on the crystal structure of retinal and isomerized the model by twisting the C12-C13=C14-C15 dihedral step by step using molecular dynamics simulation. The conformational changes revealed the all-trans to 13-cis photoisomerization of the retinal chromophore cannot open the channel. There is no water influx, and a pre-opened K-like intermediate after photoisomerization of retinal is formed. During the opening of the ion channel, proton transfer occurs between E68 and D234. Steered molecular dynamics (SMD) and umbrella sampling indicated that the E68 and D234 were the key residues for chloride-ion conducting. We propose a revised channel opening pathway model of GtACR1 after analyzing (de)protonation of E68 and D234. Reprotonation of D234 will result in two different early L intermediates, named L1-like and L 1 '-like, which correspond to the L 1 and L 1 ' intermediates reported in a recent study. Simulation results showed that L 1 -like may convert by parallel paths into L 1 '-like and L 2 -like states. This model provides conformational details for the intermediate as well. [ABSTRACT FROM AUTHOR]

Fluorescent Proteins are widely studied for their multiple applications in technological and biotechnological fields. Despite this, they continue to represent a challenge in terms of a complete understanding of all the non-equilibrium photo-induced processes that rule their properties. In this context, a theoretical-computational approach can support experimental results in unveiling and understanding the processes taking place after electronic excitation. A non-standard cyan fluorescent protein, psamFP488, is characterized by an absorption maximum that is blue-shifted in comparison to other cyan fluorescent proteins. This protein is characterized by an extended Stokes shift and an ultrafast (170 fs) excited state proton transfer. In this work, a theoretical-computational study, including excited state ab initio dynamics, is performed to help understanding the reaction mechanism and propose new hypotheses on the role of the residues surrounding the chromophore. Our results suggest that the proton transfer could be indirect toward the acceptor (Glu167) and involves other residues surrounding the chromophore, despite the ultrafast kinetics. [ABSTRACT FROM AUTHOR]

Polyethyleneimine (PEI), one of the non‐viral vectors of great interest for gene delivery, was investigated at all‐atom level, with particular emphasis on its branched form. We report the extension of our previously published CHARMM force field (FF) for linear PEI, with parameters optimized specifically for branched configurations. A new residue type for the branch connector is introduced and the charges and bonded parameters are derived from ab initio calculations based on a model polymer. The new FF is validated by extensive molecular dynamics simulations of solvated branched PEIs of various protonation fractions and branch lengths. The gyration radii, end‐to‐end distances, and diffusion coefficients are compared with results for linear PEIs of similar molecular weights and protonation patterns. Solvated complexes of DNA with (linear/branched) PEI were also investigated to determine favorable attachment conformations. The parametrized atomistic force field is suitable for simulations of PEI with arbitrary branching pattern, protonation, and size, and is expected to provide relevant insights regarding optimal conditions for DNA‐PEI complex formation. [ABSTRACT FROM AUTHOR]

The octadentate hydroxypyridonate ligand 3,4,3-LI(1,2-HOPO) (t-HOPO) shows strong binding affinity with actinide cations and is considered as a promising decorporation agent used to eliminate in vivo actinides, while its dynamics in its unbound and bound states in the condensed phase remain unclear. In this work, by means of MD simulations, the folding dynamics of intact t-HOPO in its neutral (t-HOPO0) and in its deprotonated state (t-HOPO4−) were studied. The results indicated that the deprotonation of t-HOPO in the aqueous phase significantly narrowed the accessible conformational space under the simulated conditions, and it was prepared in a conformation that could conveniently clamp the cations. The simulation of UIV-t-HOPO showed that the tetravalent uranium ion was deca-coordinated with eight ligating O atoms from the t-HOPO4− ligand, and two from aqua ligands. The strong electrostatic interaction between the U4+ ion and t-HOPO4− further diminished the flexibility of t-HOPO4− and confined it in a limited conformational space. The strong interaction between the U4+ ion and t-HOPO4− was also implicated in the shortened residence time of water molecules. [ABSTRACT FROM AUTHOR]

CoFe 2 O 4 is a promising catalytic material for many chemical reactions. We used ab initio molecular dynamic simulations to study the structure and reactivity of the A- and B-terminations of the low-index CoFe 2 O 4 (001) surfaces to water adsorption at room temperature. Upon adsorption, water partly dissociates on both termination with a higher dissociation degree on the A-termination (30% versus 19%). The 2-fold coordinated Fe3+(tet) in the tetrahedral voids and the 5-fold coordinated Fe3+(oct) in the octahedral voids are the main active sites for water dissociation on the A- and B-termination, respectively. Molecular water, hydroxydes, and surface OH resulting from proton transfer to surface oxygens are present on the surfaces. Both water-free surface terminations undergo reconstruction. The outermost Fe3+(tet) on the A-termination and B-termination move towards the nearby unoccupied octahedral voids. In the presence of a thin film of 32 water molecules, the reconstructions are partially and completely lifted on the A- and B-termination, respectively. [ABSTRACT FROM AUTHOR]

Colloidal fouling of polymeric membranes is still a limiting factor in the use of filtration for polyphenol recovery. In this context, understanding the self-aggregation mechanisms of tannic acid (TA) is of great importance. In this study, molecular dynamics simulations were performed to investigate the effect of pH on TA self-aggregation. The results show a non-monotonic relationship between pH and TA self-aggregation, with different mechanisms observed for different pH conditions. At an intermediate pH, the moderate deprotonation of TAs is associated with electrostatic repulsion between the molecules, resulting in the formation of aggregates composed of a small number of TAs. Then, at lower pH, fully protonated TA molecules promote the aggregation of a larger number of TAs because of the reduced electrostatic repulsion. Conversely, at higher pH, despite the increased negative charge of TAs leading to important electrostatic repulsion, the formation of cationic TA-H 3 O+-TA bridges favours aggregation, enhancing the number of TAs per aggregate in comparison to an intermediate pH. Finally, analysis of the size and density of the aggregates shows that at higher pH less dense aggregates are formed, because of repulsion between molecules, resulting in colloid particles of larger size compared to aggregates formed from the same number of molecules at low pH. These results provide valuable insights into the pH-dependent mechanisms of TA self-aggregation, which are crucial for adjusting operating conditions to control membrane fouling and for designing effective filtration processes. [Display omitted] • Molecular Dynamic simulations revealed a non-monotonic effect of pH on tannic acid (TA) self-aggregation. • At low pH, fully protonated TAs promote TA-TA interactions and the formation of large aggregates. • The formation of TA-H 3 O+-TA bridges explained the large aggregates found at high pH. • Electrostatic repulsion induced by negatively charged TA increased with pH leading to the formation of less dense aggregates. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sodium aluminosilicate glass – water interfacial interaction investigated by using reactive MD simulations. • Glass composition and temperature effect investigated. • Hydrolysis, ion-exchange reactions, and proton transfer reaction mechanisms identified. • Proton transfer facilitates water diffusion into the glass bulk through Si-OH rather than Al-OH. • Hydrolysis reactions shows preference on Al-O-Al and Al-O-Si than Si-O-Si linkages. Reactive molecular dynamics simulations were performed to investigate interfacial reaction mechanisms of sodium aluminosilicate (NAS) glass with water. Six NAS glass-water interfacial models for glasses with varying Al 2 O 3 /Na 2 O ratios were simulated using the Diffusive Charge Reactive Potential (DCRP) at different temperatures (298 K, 323 K, 343 K, 363 K) for up to 4 ns. Hydrolysis, ion-exchange, and proton transfer reactions at the interfaces were observed and analyzed. It was found that the hydrolysis of Al-O-Si and Al-O-Al happens more easily than that of Si-O-Si. Formation of Al-(OH)-Si or Al-(OH)-Al intermediates or penta-coordinated Al was found to precede the Al-O-Al/Si bond breakage. Proton transfer facilitates water diffusion into the glass bulk mainly through Si-OH rather than Al-OH. Surface silanol concentration depends both on the temperature and alumina content. The initial reaction rates (t < 500 ps) for silanol formation at different temperatures were calculated and showed a decrease in reaction rate for glasses with higher alumina at all temperatures. [ABSTRACT FROM AUTHOR]

We present a new concept of free energy calculations of chemical reactions by means of extended sampling molecular dynamics simulations. Biasing potentials are applied on partial atomic charges, which may be combined with atomic coordinates either in a single collective variable or in multi-dimensional biasing simulations. The necessary additional gradients are obtained by solving coupled-perturbed equations within the approximative density-functional tight-binding method. The new computational scheme was implemented in a combination of Gromacs and Plumed. As a prospective application, proton-coupled electron transfer in a model molecular system is studied. Two collective variables are introduced naturally, one for the proton transfer and the other for the electron transfer. The results are in qualitative agreement with the extended free simulations performed for reference. Free energy minima as well as the mechanism of the process are identified correctly, while the topology of the transition region and the height of the energy barrier are only reproduced qualitatively. The application also illustrates possible difficulties with the new methodology. These may be inefficient sampling of spatial coordinates when atomic charges are biased exclusively and a decreased stability of the simulations. Still, the new approach represents a viable alternative for free energy calculations of a certain class of chemical reactions, for instance a proton-coupled electron transfer in proteins. [ABSTRACT FROM AUTHOR]

Although they have been widely used as models for oxide surfaces, the deprotonation behaviors of the Keggin-ions (MeAl127+) and typical oxide surfaces are very different. On Keggin-ions, the deprotonation occurs over a very narrow pH range at odds with the broad charging curve of larger oxide surfaces. Depending on the Me concentration, the deprotonation curve levels off sooner (high Me concentration) or later (for low Me concentration). The leveling off shows the onset of aggregation before which the Keggin-ions are present as individual units. We show that the atypical titration data previously observed for some GaAl12 solutions in comparison to the originally reported data can be explained by the presence of Ga2Al11 ions. The pKa value of aquo-groups bound to octahedral Ga was determined from ab initio molecular dynamics simulations relative to the pure GaAl12 ions. Using these results within a surface complexation model, the onset of deprotonation of the crude solution is surprisingly well predicted and the ratio between the different species is estimated to be in the proportion 20 (Ga2Al11) : 20 (Al13) : 60 (GaAl12). [ABSTRACT FROM AUTHOR]

Cytochrome c oxidase is a membrane protein of the respiratory chain that consumes protons and molecular oxygen to produce water and uses the resulting energy to pump protons across the membrane. Our molecular dynamics simulations with an excess proton located at different positions in one of the proton-conducting channels, the K-channel, show a clear dependence of the number of water molecules inside the channel on the proton position. A higher hydration level facilitates the formation of hydrogen-bonded chains along which proton transfer can occur. However, a sufficiently high hydration level for such proton transport is observed only when the excess proton is located above S365, i.e., the lower third of the channel. From the channel entrance up to this point, proton transport is via water molecules as proton carriers. These hydronium ions move with their surrounding water molecules, up to K362, filling and widening the channel. The conformation of K362 depends on its own protonation state and on the hydration level, suggesting its role to be proton transport from a hydronium ion at the height of K362 to the upper part of the channel via a conformational change. The protonation-dependent conformational dynamics of E101 at the bottom of the channel renders proton transfer via E101 unlikely. Instead, its role is rather that of an amplifier of H96's proton affinity, suggesting H96 as the initial proton acceptor. [ABSTRACT FROM AUTHOR]

The Nazarov cyclization is investigated in solution and within K12[Ga4L6] supramolecular organometallic cage by means of computational methods. The reaction needs acidic condition in solution but works at neutral pH in the presence of the metallocage. The reaction steps for the process are analogous in both media: (a) protonation of the alcohol group, (b) water loss and (c) cyclization. The relative Gibbs energies of all the steps are affected by changing the environment from solvent to the metallocage. The first step in the mechanism, the alcohol protonation, turns out to be the most critical one for the acceleration of the reaction inside the metallocage. In order to calculate the relative stability of protonated alcohol inside the cavity, we propose a computational scheme for the calculation of basicity for species inside cavities and can be of general use. These results are in excellent agreement with the experiments, identifying key steps of catalysis and providing an in‐depth understanding of the impact of the metallocage on all the reaction steps. [ABSTRACT FROM AUTHOR]