Water dynamics and sum-frequency generation spectra at electrode/aqueous electrolyte interfaces.

The dynamics of water at interfaces between an electrode and an electrolyte is essential for the transport of redox species and for the kinetics of charge transfer reactions next to the electrode. However, while the effects of electrode potential and ion concentration on the electric double layer structure have been extensively studied, a comparable understanding of dynamical aspects is missing. Interfacial water dynamics presents challenges since it is expected to result from the complex combination of water-water, water-electrode and water-ion interactions.

Ultrafast Rotational and Translational Energy Relaxation in Neat Liquids.

The excess energy flow pathways during rotational and translational relaxation induced by rotational or translational excitation of a single molecule of and within each of four different neat liquids (HO, MeOH, CCl, and CH) are studied using classical molecular dynamics simulations and energy flux analysis. For all four liquids, the relaxation processes for both types of excitation are ultrafast, but the energy flow is significantly faster for the polar, hydrogen-bonded (H-bonded) liquids HO and MeOH. Whereas the majority of the initial excess energy is transferred into hindered rotations (librations) for rotational excitation in the H-bonded liquids, an almost equal efficiency for transfer to translational and rotational motions is observed in the nonpolar, non-H-bonded liquids CCl and CH.

Electron Flow Characterization of Charge Transfer for Carbonic Acid to Strong Base Proton Transfer in Aqueous Solution.

Protonation of the strong base methylamine CHNH by carbonic acid HCO in aqueous solution, HOCOOH···NHCH → HOCOO···HNHCH, has been previously studied ( 2016, 109, 2271-2280; 2016, 109, 2281-2290) via Car-Parinnello molecular dynamics. This proton transfer (PT) reaction within a hydrogen (H)-bonded complex was found to be barrierless and very rapid, with key reaction coordinates comprising the proton coordinate, the H-bond separation , and a solvent coordinate, reflecting the water solvent rearrangement involved in the neutral to ion pair conversion. In the present work, the reaction's charge flow aspects are analyzed in detail, especially a description via Mulliken charge transfer for PT (MCTPT).

A Model Electron Transfer Reaction in Confined Aqueous Solution.

Liquid water confined within nanometer-sized channels exhibits a strongly reduced local dielectric constant perpendicular to the wall, especially at the interface, and this has been suggested to induce faster electron transfer kinetics at the interface than in the bulk. We study a model electron transfer reaction in aqueous solution confined between graphene sheets with classical molecular dynamics. We show that the solvent reorganization energy is reduced at the interface compared to the bulk, which explains the larger rate constant.

Confined Water's Dielectric Constant Reduction Is Due to the Surrounding Low Dielectric Media and Not to Interfacial Molecular Ordering.

Liquid water confined within nanometer-sized channels exhibits a surprisingly low dielectric constant along the direction orthogonal to the channel walls. This is typically assumed to result from a pronounced heterogeneity across the sample: the dielectric constant would be bulk-like everywhere except at the interface, where it would be dramatically reduced by strong restrictions on interfacial molecules. Here we study the dielectric properties of water confined within graphene slit channels via classical molecular dynamics simulations.

Extracellular Ca-Sensing Fluorescent Protein Biosensor Based on a Collagen-Binding Domain.

The importance of extracellular gradients of biomolecules is increasingly appreciated in the processes of tissue development and regeneration, in health and disease. In particular, the dynamics of extracellular calcium concentration is rarely studied. Here, we present a low affinity Ca biosensor based on Twitch-2B fluorescent protein fused with the cellulose- and collagen-binding peptides.

Solvation Dynamics in Water. 4. On the Initial Regime of Solvation Relaxation.

It is shown, by means of numerical and analytic work, that initial molecular momenta play little significant role in the initial fast solvation relaxation that follows electronic excitation of, and charge creation for, a standard model system of a solute in water. Instead, the nonequilibrium dynamics are predominantly described by noninertial "steering" by the torques directly generated by the newly created charge distribution. It is this process that largely overcomes inertia and drives the relaxation dynamics on a time scale of a few tens of femtoseconds in the key initial regime of the dynamics.

Water dynamics at electrified graphene interfaces: a jump model perspective.

The reorientation dynamics of water at electrified graphene interfaces was recently shown [J. Phys. Chem.

Water Structure, Dynamics, and Sum-Frequency Generation Spectra at Electrified Graphene Interfaces.

The properties of water at an electrified graphene electrode are studied via classical molecular dynamics simulations with a constant potential approach. We show that the value of the applied electrode potential has dramatic effects on the structure and dynamics of interfacial water molecules. While a positive potential slows down the reorientational and translational dynamics of water, an increasing negative potential first accelerates the interfacial water dynamics before a deceleration at very large magnitude potential values.

Insights into pancreatic β cell energy metabolism using rodent β cell models.

Mitochondrial diabetes is primarily caused by β-cell failure, a cell type whose unique properties are important in pathogenesis. By reducing glucose, we induced energetic stress in two rodent β-cell models to assess effects on cellular function. Culturing rat insulin-secreting INS-1 cells in low glucose conditions caused a rapid reduction in whole cell respiration, associated with elevated mitochondrial reactive oxygen species production, and an altered glucose-stimulated insulin secretion profile.

Dynamical Recrossing in the Intercalation Process of the Anticancer Agent Proflavine into DNA.

Intercalation into DNA is the interaction mode of some anthracycline antibiotics. Recently, the molecular mechanism of this process was explored using the static free energy landscape. Here we explore the dynamical effects in the intercalation of proflavine into DNA by calculating the transmission coefficient κ-providing a measure of the departure from transition state theory for the reaction rate constant-by examination of the recrossing events at the transition state.

Intact carbonic acid is a viable protonating agent for biological bases.

Carbonic acid HCO (CA) is a key constituent of the universal CA/bicarbonate/CO buffer maintaining the pH of both blood and the oceans. Here we demonstrate the ability of intact CA to quantitatively protonate bases with biologically-relevant pKs and argue that CA has a previously unappreciated function as a major source of protons in blood plasma. We determine with high precision the temperature dependence of pK(CA), pK(T) = -373.

Benzimidazoles as Metal-Free and Recyclable Hydrides for CO Reduction to Formate.

We report a novel metal-free chemical reduction of CO by a recyclable benzimidazole-based organo-hydride, whose choice was guided by quantum chemical calculations. Notably, benzimidazole-based hydride donors rival the hydride-donating abilities of noble-metal-based hydrides such as [Ru(tpy)(bpy)H] and [Pt(depe)H]. Chemical CO reduction to the formate anion (HCOO) was carried out in the absence of biological enzymes, a sacrificial Lewis acid, or a base to activate the substrate or reductant.

Renewable Hydride Donors for the Catalytic Reduction of CO: A Thermodynamic and Kinetic Study.

Increasing atmospheric CO concentration and dwindling fossil fuel supply necessitate the search for efficient methods for CO conversion to fuels. Assorted studies have shown pyridine and its derivatives capable of (photo)electrochemically reducing CO to methanol, and some mechanistic interpretations have been proposed. Here, we analyze the thermodynamic and kinetic aspects of the efficacy of pyridines as hydride-donating catalytic reagents that transfer hydrides via their dihydropyridinic form.

High-Throughput Analysis of Mitochondrial Oxygen Consumption.

Interest in the investigation of mitochondrial dysfunction has seen a resurgence over recent years due to the implication of such dysfunction in both drug-induced toxicity and a variety of disease states. Here we describe a methodology to assist in such investigations whereby the oxygen consumption of isolated mitochondria is assessed in a high-throughput fashion using a phosphorescent oxygen-sensitive probe , standard microtiter plates, and plate reader detection. The protocols provided describe the required isolation procedures, initial assay optimization, and subsequent compound screening.

Bringing in vitro analysis closer to in vivo: Studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling.

Doxorubicin (DOX) is a chemotherapeutic agent of which the medical use is limited due to cardiotoxicity. While acute cardiotoxicity is reversible, chronic cardiotoxicity is persistent or progressive, dose-dependent and irreversible. While DOX mechanisms of action are not fully understood yet, 3 toxicity processes are known to occur in vivo: cardiomyocyte dysfunction, mitochondrial dysfunction and cell death.

Predicting Hydride Donor Strength via Quantum Chemical Calculations of Hydride Transfer Activation Free Energy.

We propose a method to approximate the kinetic properties of hydride donor species by relating the nucleophilicity (N) of a hydride to the activation free energy ΔG of its corresponding hydride transfer reaction. N is a kinetic parameter related to the hydride transfer rate constant that quantifies a nucleophilic hydridic species' tendency to donate. Our method estimates N using quantum chemical calculations to compute ΔG for hydride transfers from hydride donors to CO in solution.

Nuclear Quantum Effects in Water Reorientation and Hydrogen-Bond Dynamics.

We combine classical and ring polymer molecular dynamics simulations with the molecular jump model to provide a molecular description of the nuclear quantum effects (NQEs) on water reorientation and hydrogen-bond dynamics in liquid HO and DO. We show that while the net NQE is negligible in DO, it leads to a ∼13% acceleration in HO dynamics compared to a classical description. Large angular jumps-exchanging hydrogen-bond partners-are the dominant reorientation pathway (just as in a classical description); the faster reorientation dynamics arise from the increased jump rate constant.

Perspective: Structure and ultrafast dynamics of biomolecular hydration shells.

The structure and function of biomolecules can be strongly influenced by their hydration shells. A key challenge is thus to determine the extent to which these shells differ from bulk water, since the structural fluctuations and molecular excitations of hydrating water molecules within these shells can cover a broad range in both space and time. Recent progress in theory, molecular dynamics simulations, and ultrafast vibrational spectroscopy has led to new and detailed insight into the fluctuations of water structure, elementary water motions, and electric fields at hydrated biointerfaces.

Dihydropteridine/Pteridine as a 2H/2e Redox Mediator for the Reduction of CO to Methanol: A Computational Study.

Conflicting experimental results for the electrocatalytic reduction of CO to CHOH on a glassy carbon electrode by the 6,7-dimethyl-4-hydroxy-2-mercaptopteridine have been recently reported [ J. Am. Chem.

Water Dynamics in the Hydration Shells of Biomolecules.

The structure and function of biomolecules are strongly influenced by their hydration shells. Structural fluctuations and molecular excitations of hydrating water molecules cover a broad range in space and time, from individual water molecules to larger pools and from femtosecond to microsecond time scales. Recent progress in theory and molecular dynamics simulations as well as in ultrafast vibrational spectroscopy has led to new and detailed insight into fluctuations of water structure, elementary water motions, electric fields at hydrated biointerfaces, and processes of vibrational relaxation and energy dissipation.

Solvation Dynamics in Liquid Water. III. Energy Fluxes and Structural Changes.

In previous installments it has been shown how a detailed analysis of energy fluxes induced by electronic excitation of a solute can provide a quantitative understanding of the dominant molecular energy flow channels characterizing solvation-and in particular, hydration- relaxation dynamics. Here this work and power approach is complemented with a detailed characterization of the changes induced by such energy fluxes. We first examine the water solvent's spatial and orientational distributions and the assorted energy fluxes in the various hydration shells of the solute to provide a molecular picture of the relaxation.

Non-adiabatic transition probability dependence on conical intersection topography.

We derive a closed form analytical expression for the non-adiabatic transition probability for a distribution of trajectories passing through a generic conical intersection (CI), based on the Landau-Zener equation for the non-adiabatic transition probability for a single straight-line trajectory in the CI's vicinity. We investigate the non-adiabatic transition probability's variation with topographical features and find, for the same crossing velocity, no intrinsic difference in efficiency at promoting non-adiabatic decay between peaked and sloped CIs, a result in contrast to the commonly held view. Any increased efficiency of peaked over sloped CIs is thus due to dynamical effects rather than to any increased transition probability of topographical origin.