The Journal of Physical Chemistry B最新文献

Cryopreservation is the preservation and storage of biomaterials using low temperatures. There are several approaches to cryopreservation, and these often include the use of cryoprotectants, which are solutes used to lower the freezing point of water. Isochoric (constant-volume) cryopreservation is a form of cryopreservation that has been gaining interest over the past 18 years. This method utilizes the anomalous nature of water in that it expands as it freezes. The expansion of ice on freezing is used to induce a pressure in the system that limits ice growth. In this work, we use Gibbsian thermodynamics, the Elliott et al. multisolute osmotic virial equation, the Feistel and Wagner correlation for ice Ih, and the Grenke and Elliott correlation for the thermodynamic properties of liquid water at low temperatures and high pressures to predict how the pressure, volume fraction of ice, and solute concentration in the unfrozen fraction change as the solution is cooled isochorically. We then verified our model by predicting experimental results for saline solutions and ternary aqueous solutions containing NaCl and organic compounds commonly used as cryoprotectants: glycerol, ethylene glycol, propylene glycol, and dimethyl sulfoxide. We found that our model accurately predicts experimental data that were collected for cryoprotectant concentrations as high as 5 M, and temperatures as low as −25 °C. Since we have shown that our liquid water correlation, on which this work was based, makes accurate predictions to −70 °C, as long as the pressure is not higher than 400 MPa, we anticipate that the prediction methods presented in this work will be accurate down to −70 °C. In this work we also modeled how sealing the isochoric chamber at room temperature versus at the nucleation temperature impacts isochoric freezing. The prediction methods developed in this work can be used in the future design of isochoric cryopreservation experiments and protocols.

Noncovalent interactions, particularly hydrogen bonding, play a pivotal role in determining the structural stability and functional properties of molecules, including bioactive compounds like resveratrol. This study focuses on the hydrogen-bonding behavior and other noncovalent interactions in gas-phase resveratrol-ethanol (EtOH) and resveratrol-methanol (MtOH) complexes, referred to as System 1 and System 2, respectively. These systems were optimized using the ωB97XD functional and cc-pVDZ basis set, providing a detailed picture of their stability and intermolecular interactions. By employing advanced methods such as Domain-Based Local Pair Natural Orbital Coupled Cluster (DLPNO–CCSD)(T) for energy decomposition, natural bond orbital (NBO) for charge analysis, atoms in molecule (AIM) for electron density topology, and noncovalent interaction (NCI) techniques, we decompose interaction energies into meaningful components like electrostatic, dispersion, and exchange-repulsion. The findings indicate that, while hydrogen bonding contributes to the stability of these complexes, London dispersion and other attractive interactions are substantial factors as well. The resveratrol-EtOH and resveratrol-MtOH systems demonstrate a robust electronic environment with significant contributions from various intermolecular forces, underscoring the importance of noncovalent interactions in stabilizing bioactive compounds. This study adds to our understanding of molecular interactions in resveratrol complexes, with potential implications for medicinal chemistry and material science, particularly where solvation effects are critical.

In this study, we investigated the stability of the fully activated conformation of the orexin receptor 2 (OX₂R) embedded in a pure POPC bilayer using MD simulations. Various thermodynamic ensembles (i.e., NPT, NVT, NVE, NPAT, μVT, and NPγT) were employed to explore the dynamical heterogeneity of the system in a comprehensive way. In addition, informational similarity metrics (e.g., Jensen-Shannon divergence) as well as Markov state modeling approaches were utilized to elucidate the receptor kinetics. Special attention was paid to assessing surface tension within the simulation box, particularly under NPγT conditions, where 21 nominal surface tension constants were evaluated. Our findings suggest that traditional thermodynamic ensembles such as NPT may not adequately control physical properties of the POPC membrane, impacting the plausibility of the OX₂R model. In general, the performed study underscores the importance of employing the NPγT ensemble for computational investigations of membrane-embedded receptors, as it effectively maintains zero surface tension in the simulated system. These results offer valuable insights for future research aimed at understanding receptor dynamics and designing targeted therapeutics.

Ferrocene is commonly used as an internal redox couple in electrochemical measurements. Therefore, understanding how the absolute oxidation potential of ferrocene is modulated by different solvents and ion concentrations is important for the comparison of experimental measurements between different electrochemical systems. While standard implicit solvation models may provide relatively good predictions in bulk solvents, they lack the ability to describe ion coordination effects that can substantially alter redox potentials in practical electrolyte systems. In this work, we utilize molecular dynamics simulations to compute absolute oxidation potentials for the ferrocene and decamethylferrocene redox couple in bulk solvents of water, acetonitrile, 1,2-dichloroethane, and trichloromethane, as well as organic electrolytes consisting of mixtures of [BMIM⁺][BF₄^–] ionic liquid and acetonitrile and 1,2-dichloroethane solvents, for a wide range of ion concentrations. The goals are twofold: first, for the bulk solvents, we compare and evaluate the consistency of redox potential predictions for polarizable and nonpolarizable force fields from explicit solvent, free energy simulations, with predictions from an implicit solvent model. Second, we evaluate how ion coordination within the organic electrolytes modulates the redox potential of ferrocene and decamethylferrocene as a function of the ionic concentration and solvent dielectric constant. Utilizing linear response theory, we analyze the solvation contribution to the redox potential in terms of distributions of anion coordination number and how the anion coordination modulates the vertical ionization energy. We show that inclusion of liquid-vacuum interfacial potentials is essential for consistent prediction/interpretation of redox potentials across different solvents and force fields in order to compensate for the artificial quadrupole trace contribution to the solute cavity interfacial potential; this important consideration was previously proposed by Harder and Roux [J. Chem. Phys. 2008, 129, 234706].

Simulating excited-state dynamics or computing spectra for molecules in condensed phases requires sampling the ground state to generate initial conditions. Initial conditions (or snapshots for spectra) are typically produced by QM/MM Boltzmann sampling following MM equilibration or optimization. Given the switch from a MM to a QM/MM potential energy surface, one should discard a set period of time (which we call the “healing time”) from the beginning of the QM/MM trajectory. Ideally, the healing time is as short as possible (to avoid unnecessary computational effort), but long enough to equilibrate to the QM/MM ground state distribution. Healing times in previous studies range from tens of femtoseconds to tens of picoseconds, suggesting the need for guidelines to choose a healing time. We examine the effect of healing time on the nonadiabatic dynamics and spectrum of a first-generation Donor–Acceptor Stenhouse Adduct in chloroform. Insufficient healing times skew the branching ratio of ground state products and alter the relaxation time for one pathway. The influence of the healing time on the absorption spectrum is less pronounced, warning that the spectrum is not a sensitive indicator for the quality of a set of initial conditions for dynamics. We demonstrate that a reasonable estimate for the healing time can be obtained by monitoring the solute temperature during the healing trajectory. We suggest that this procedure should become standard practice for determining healing times to generate initial conditions for nonadiabatic QM/MM simulations in large molecules and condensed phases.

The global health crisis triggered by the SARS-CoV-2 virus has highlighted the urgent need for effective treatments. As existing drugs are not specifically targeted at this virus, there is a growing interest in exploring natural antimicrobial peptides such as defensin as potential therapeutic options. Human β defensin type 2 (hBD-2), which is a cationic cysteine-rich peptide, serves as the initial barrier against bacterial and fungal invaders in mammals. It can bind with Spike-RBD and occupy the same site as the ACE2 receptor, thereby hindering viral entry into cells expressing ACE2. To explore the effect of different point mutations on the binding of hBD-2 with RBD, the binding dynamics and interactions between hBD-2 point mutants with RBD were studied and compared with that of RBD&hBD-2 wild-type complex. In total, 247 hBD-2 point mutants were built with the mutation sites at the binding region of hBD-2 (RES18–30) with the RBD of CoV-2. All-atom molecular dynamics simulations were carried out on RBD binding with hBD-2 point mutants. Analysis based on root-mean-square deviation (RMSD), hydrogen bonds analysis, and binding free energy using the MM/PBSA method revealed that many point mutants of hBD-2 exhibit weaker binding with RBD compared to the wild type; however, a subset of mutants, including C20I, C20K, R22W, R23H, R23L, Y24L, K25F, K25H, G28Y, T29R, and C30K, displayed enhanced binding with RBD. The findings can offer insights designing hBD-2-based novel drugs to combat SARS-CoV-2 in the long term.

Modeling polymer brushes is essential for understanding their complex behavior at surfaces and interfaces, enabling the design of materials with tunable properties. We present a computational protocol to model polymer brushes composed of grafted, brush-like chains of the charged polymer poly(N,N-dimethylaminoethyl methacrylate) (p(DMAEMA)) using an all-atom representation that captures detailed molecular interactions and structural properties. The approach is flexible and non-grid-based and allows for randomized strand configurations and the incorporation of periodic boundary conditions, enabling the construction of asymmetric polymer brush setups. An atactic p(DMAEMA) configuration is demonstrated as an example, though the protocol can be readily adapted to construct other brush-like polymer systems with varying tacticities or compositions, depending on the pH environment. Furthermore, this can be extended to stimuli-responsive materials, which generate conformation or charge upon changes in pH value or other external triggers. Molecular dynamics simulations are then employed to gain insights into the conformational behavior of the grafted p(DMAEMA) brushes and their surrounding aqueous environment, as well as their response to temperature, protonation, and variations in grafting densities, in terms of the solvent-accessible surface area, radius of gyration, and radial distribution functions. This versatile protocol provides a robust tool for simulating and analyzing the properties of diverse polyelectrolyte polymer brush systems and also as composite materials.

Since the advent of time-resolved spectroscopy based on precision frequency technology of laser sources, it has been considered an alternative way to study dynamic processes in photochemical systems. This Perspective introduces asynchronous and interferometric nonlinear spectroscopy (AI-NS), a spectroscopic technique that combines asynchronously generated laser pulses and interferometric detection, offering an unprecedented temporal dynamic range with high spectral resolution and rapid data acquisition capabilities. By eliminating the need for mechanical delay stages, AI-NS facilitates the rapid collection of time-resolved data on dynamics ranging from femtoseconds to nanoseconds while simultaneously distinguishing frequency-dependent responses. Here, we detail the technical methodology of AI-NS and explore its applications to the studies of various systems, including semiconductors and biological systems. Additionally, we highlight prospective advancements, such as integration with multidimensional spectroscopy techniques. AI-NS not only expands the scope of spectroscopic analysis but also opens new avenues for the exploration of diverse materials and molecular systems.

We report a computational protocol for simulating electric field gradient dynamics around Na⁺ cations in mixtures of 1-ethyl-3-methylimidazolium tetrafluoroborate ([Im₂₁][BF₄]) and water validated by comparison to measurements of nuclear magnetic resonance (NMR) T₁ relaxation times. Our protocol combines classical molecular dynamics simulations of a scaled charge model of [Im₂₁][BF₄] and TIP4Pew water to generate the electric field gradient (EFG) correlation function, C_EFG(t), with quantum chemical calculations for determining the EFG variance $⟨V_{zz}^2⟩$. Although we demonstrate that the Sternheimer approximation is as valid in these mixtures as it is in neat water, we do not recommend using the Sternheimer approximation as it underestimates $⟨V_{zz}^2⟩$ by ∼10% compared to a set of computationally efficient density functional theory calculations. Our protocol is capable of reproducing both the composition- and temperature-dependence of T₁ over the full range of experimentally accessible [Im₂₁][BF₄]/water compositions and a temperature range of 285–350 K. We also show that scaling the [Im₂₁][BF₄] charges does not simply speed up the dynamics of the solvent, but has effects on the shape of C_EFG(t). Following validation of our protocol, we analyze the shape and relaxation times of C_EFG(t) to show that the mechanism by with T₁ changes is different when the composition of the mixture varies compared to changes in temperature. As composition changes, the balance between inertial and diffusive relaxation alters, whereas temperature only affects the time scale of the diffusion portion of the relaxation. We also show that solvation shell of Na⁺ in these mixtures is significantly more labile than in neat [Im₂₁][BF₄] and that water and BF₄^– anions compete to be in the Na⁺ solvation shell. This validated computational protocol opens the door to more detailed interpretation of NMR T₁ relaxation experiments of monatomic ions in complex liquid environments.

Computationally designed 29-residue peptides yield tetra-α-helical bundles with D₂ symmetry. The "bundlemers" can be bifunctionally linked via thiol-maleimide cross-links at their N-termini, yielding supramolecular polymers with unusually large, micrometer-scale persistence lengths. To provide a molecularly resolved understanding of these systems, all-atom molecular modeling and simulations of linked bundlemers in explicit solvent are presented. A search over relative orientations of the bundlemers identifies a structure, wherein at the bundlemer-bundlemer interface, interior hydrophobic residues are in contact, and α-helices are aligned with a pseudocontiguous α-helix that spans the interface. Calculation of a potential of mean force confirms that the structure in which the bundlemers are in contact and colinearly aligned is a stable minimum. Analyses of hydrogen bonds and hydrophobic complementarity highlight the complementary interactions at the interface. The molecular insight provided reveals the molecular origins of bundlemer alignment within the supramolecular polymers.