Polarizable Model Research Articles

Induced Polarization in Molecular Dynamics Simulations of the 5-HT3 Receptor Channel.

Ion channel proteins form water-filled nanoscale pores within lipid bilayers, and their properties are dependent on the complex behavior of water in a nanoconfined environment. Using a simplified model of the pore of the 5-HT3 receptor (5HT3R) which restrains the backbone structure to that of the parent channel protein from which it is derived, we compare additive with polarizable models in describing the behavior of water in nanopores. Molecular dynamics simulations were performed with four conformations of the channel: two closed state structures, an intermediate state, and an open state, each embedded in a phosphatidylcholine bilayer. Water density profiles revealed that for all water models, the closed and intermediate states exhibited strong dewetting within the central hydrophobic gate region of the pore. However, the open state conformation exhibited varying degrees of hydration, ranging from partial wetting for the TIP4P/2005 water model to complete wetting for the polarizable AMOEBA14 model. Water dipole moments calculated using polarizable force fields also revealed that water molecules remaining within dewetted sections of the pore resemble gas phase water. Free energy profiles for Na+ and for Cl– ions within the open state pore revealed more rugged energy landscapes using polarizable force fields, and the hydration number profiles of these ions were also sensitive to induced polarization resulting in a substantive reduction of the number of waters within the first hydration shell of Cl– while it permeates the pore. These results demonstrate that induced polarization can influence the complex behavior of water and ions within nanoscale pores and provides important new insights into their chemical properties.

Nonresonant Polarized Raman Spectra Calculations of Nitrogen-Doped Single-Walled Carbon Nanotubes: Diameter, Chirality, and Doping Concentration Effects.

Raman spectra of nitrogen-doped single-walled carbon nanotubes are calculated using the spectral moment's method combined with the bond polarizability model. The influence of the nanotube diameter and chirality is investigated. We also address the important question of the effect of the N-doping concentration, and we propose an equation to estimate the doping concentration from the knowledge of the tube diameter and the frequency of the radial breathing mode.

Nature of Alkali Ion-Water Interactions: Insights from Many-Body Representations and Density Functional Theory. II.

Interaction energies of alkali ion-water dimers, M+(H2O), and trimers, M+(H2O)2, with M = Li, Na, K, Rb, and Cs, are investigated using various many-body potential energy functions and exchange-correlation functionals selected across the hierarchy of density functional theory approximations. Analysis of interaction energy decompositions indicates that close-range interactions such as Pauli repulsion, charge transfer, and charge penetration must be captured in order to reproduce accurate interaction energies. In particular, it is found that simple classical polarizable models must be supplemented with dedicated terms which account for these close-range interactions in order to achieve chemical accuracy. It is also found that the exchange-correlation functionals mostly differ from each other in their Pauli repulsion + dispersion energies and, hence, benefit from the inclusion of nonlocal terms such as Hartree-Fock exchange and dependence on the electronic kinetic energy density in order to reproduce the interactions that contribute to this term, namely, Pauli repulsion and intermediate-range dispersion. As a continuation of the analysis performed in J. Chem. Theory Comput. 2019, 15, 2983, 10.1021/acs.jctc.9b00064, we make comparisons between findings for alkali ion-water interactions with those for halide-water interactions.

Ergodicity Breaking in Thermal Biological Electron Transfer? Cytochrome C Revisited II

It was recently suggested that cytochrome c operates in an ergodicity-breaking regime characterized by unusually large energy gap thermal fluctuations and associated reorganization free energies for heme oxidation of up to 3.0 eV. The large fluctuations were reported to lower activation free energy for oxidation of the heme cofactor by almost a factor of 2 compared to the case where ergodicity is maintained. Our group has recently investigated this claim computationally at several levels of theory and found no evidence for such large energy gap fluctuations. Here we address the points of our earlier work that have raised criticism and we also extend our previous investigation by considering a simple linear polarizability model for cytochrome c oxidation. We find very consistent results among all our computational approaches, ranging from classical molecular dynamics, to the linear polarizability model to QM(PMM)/MM to full QM(DFT)/MM electrostatic emdedding. None of them support the notion of very large energy gap fluctuations or ergodicity breaking. The deviation between our simulations and the ones reported in [ J. Phys. Chem. B 2017, 121, 4958] is traced back to rather large electric fields at the Fe site of the heme c cofactor in that study, not seen in our simulations, neither with the AMBER nor with the CHARMM force field. While ergodicity breaking effects may well occur in other biological ET, our numerical evidence suggests that this is not the case for cytochrome c.

Synthesis, experimental and in silico studies of N-fluorenylmethoxycarbonyl-O-tert-butyl-N-methyltyrosine, coupled with CSD data: a survey of interactions in the crystal structures of Fmoc-amino acids.

Recently, fluorenylmethoxycarbonyl (Fmoc) amino acids (e.g. Fmoc-tyrosine or Fmoc-phenylalanine) have attracted growing interest in biomedical research and industry, with special emphasis directed towards the design and development of novel effective hydrogelators, biomaterials or therapeutics. With this in mind, a systematic knowledge of the structural and supramolecular features in recognition of those properties is essential. This work is the first comprehensive summary of noncovalent interactions combined with a library of supramolecular synthon patterns in all crystal structures of amino acids with the Fmoc moiety reported so far. Moreover, a new Fmoc-protected amino acid, namely, 2-{[(9H-fluoren-9-ylmethoxy)carbonyl](methyl)amino}-3-{4-[(2-hydroxypropan-2-yl)oxy]phenyl}propanoic acid or N-fluorenylmethoxycarbonyl-O-tert-butyl-N-methyltyrosine, Fmoc-N-Me-Tyr(t-Bu)-OH, C29H31NO5, was successfully synthesized and the structure of its unsolvated form was determined by single-crystal X-ray diffraction. The structural, conformational and energy landscape was investigated in detail by combined experimental and in silico approaches, and further compared to N-Fmoc-phenylalanine [Draper et al. (2015). CrystEngComm, 42, 8047-8057]. Geometries were optimized by the density functional theory (DFT) method either in vacuo or in solutio. The polarizable conductor calculation model was exploited for the evaluation of the hydration effect. Hirshfeld surface analysis revealed that H...H, C...H/H...C and O...H/H...O interactions constitute the major contributions to the total Hirshfeld surface area in all the investigated systems. The molecular electrostatic potentials mapped over the surfaces identified the electrostatic complementarities in the crystal packing. The prediction of weak hydrogen-bonded patterns via Full Interaction Maps was computed. Supramolecular motifs formed via C-H...O, C-H...π, (fluorenyl)C-H...Cl(I), C-Br...π(fluorenyl) and C-I...π(fluorenyl) interactions are observed. Basic synthons, in combination with the Long-Range Synthon Aufbau Modules, further supported by energy-framework calculations, are discussed. Furthermore, the relevance of Fmoc-based supramolecular hydrogen-bonding patterns in biocomplexes are emphasized, for the first time.

Modeling Intermolecular and Intramolecular Modes of Liquid Water Using Multiple Heat Baths: Machine Learning Approach.

The vibrational motion of molecules in dissipative environments, such as solvation and protein molecules, is composed of contributions from both intermolecular and intramolecular modes. The existence of these collective modes introduces difficulty into quantum simulations of chemical and biological processes. In order to describe the complex molecular motion of the environment in a simple manner, we introduce a system-bath model in which the intramolecular modes with anharmonic mode-mode couplings are described by a system Hamiltonian, while the other degrees of freedom, arising from the environmental molecules, are described by a heat bath. Employing a machine-learning-based approach, we determine not only the system parameters of the intramolecular modes but also the spectral distribution of the system-bath coupling to describe the intermolecular modes, using the atomic trajectories obtained from molecular dynamics (MD) simulations. The capabilities of the present approach are demonstrated for liquid water using MD trajectories calculated from the SPC/E model and the polarizable water model for intramolecular and intermolecular vibrational spectroscopies (POLI2VS) by determining the system parameters describing the symmetric-stretch, asymmetric-stretch, and bend modes with intramolecular interactions and the bath spectral distribution functions for each intramolecular mode representing the interaction with the intramolecular modes. From these results, we were able to elucidate the energy relaxation pathway between the intramolecular modes and the intermolecular modes in a nonintuitive manner.

Polarizable TIP7P Water Model with Perturbation Charges Evaluated from ABEEM.

A polarizable version of the rigid seven-site (TIP7P) water model with the atom-bond electronegativity equalization method (ABEEM) is proposed. The model uses direct polarization, where an isolated water monomer in the equilibrium geometry is assumed as a reference state and the polarization of the monomer arises from interacting with other molecules as a perturbation of the reference state. The charge on each site of the monomer splits into reference charge and perturbation charge. The perturbation charge arises only because of other reference charges. The interaction of the perturbation charge with other perturbation charges is replaced using polarization scaling to enhance the interaction of perturbation charge with the reference charges of the sites from other molecules. The perturbation charges are updated by evaluating explicit expressions once. This direct polarization is time-reversible because the charge update is independent of the charges in previous simulation steps. A Slater-type damping function moderates the short-range electrostatics to treat charge diffusion. The Ewald method corrects the long-range electrostatics both in the nuclei movement and in electronegativity equalization to diminish the size effect. The water model is parameterized by fitting the ab initio results of water clusters and the experimental results of water monomers and thermodynamic properties for liquid water. Owing to polarizability, the model performs better than the TIP7P model in terms of vaporization enthalpy, isothermal compressibility, and shear viscosity of the liquid phase. It performs better at the melting point of ice but slightly worse under critical conditions than the TIP7P model. Direct polarization has a low time complexity of O(N) and is a good choice for ABEEM to improve its computational efficiency.

The Usefulness of Spectroscopic Simulations.

This article presents a method for extracting the optical constants of homogeneous isotropic materials using the infrared spectra of that material. The method is based on using the harmonic oscillator model of molecular polarizability to obtain optical constants, then calculating the spectrum, comparing the calculated spectrum to an experimental spectrum of the material, and adjusting the model parameters until a close fit between the spectra is obtained. Corrections that need to be made to the experimental spectra in order to remove instrumental distortions are also briefly described. The remainder of the article centers on describing how the optical constants can be used to simulate spectra of that material in different experimental arrangements and the benefits that spectral simulations afford to experimentalists.

Hydrolysis and Condensation of n-BuSnCl3: Enabling Deposition of Smooth Metal Oxide Photoresist Thin Films.

Herein, we report hydrolysis and condensation chemistries of C4H9SnCl3 to molecular clusters and gel films. Precursor speciation plays a key role in film formation and quality toward realization of atomically smooth surfaces. Density functional theory investigations of C4H9SnCl3 and its reactions show that hydrolysis of the dimer (C4H9Sn)2(OH)2Cl4(H2O)2 has a high energetic penalty in the gas phase and when using a polarizable continuum solvation model based on density. These computations support our observed stability of the dimeric cluster in air, in various solvents, and through initial film deposition. It hydrolyzes and condenses to the [(C4H9Sn)12O14(OH)6]2+ dodecamer on-chip after a post film-deposition bake at 80 °C. Consequently, film surface smoothness is uniquely retained through on-wafer condensation.

Deriving a Polarizable Force Field for Biomolecular Building Blocks with Minimal Empirical Calibration.

Force field parametrization involves a complex set of linked optimization problems, with the goal of describing complex molecular interactions by using simple classical potential-energy functions that model Coulomb interactions, dispersion, and exchange repulsion. These functions comprise a set of atomic (and molecular) parameters and together with the bonded terms they constitute the molecular mechanics force field. Traditionally, many of these parameters have been fitted in a calibration approach in which experimental measures for thermodynamic and other relevant properties of small-molecule compounds are used for fitting and validation. As these approaches are laborious and time-consuming and represent an underdetermined optimization problem, we study methods to fit and derive an increasing number of parameters directly from electronic structure calculations, in order to greatly reduce possible parameter space for the remaining free parameters. In the current work we investigate a polarizable model with a higher order dispersion term for use in biomolecular simulation. Results for 49 biochemically relevant molecules are presented including updated parameters for hydrocarbon side chains. We show that our recently presented set of QM/MM derived atomic polarizabilities can be used in direct conjunction with partial charges and a higher order dispersion model that are quantum-mechanically determined, to freeze nearly all (i.e., 132 out of 138) nonbonded parameters to their quantum determined values.

Coarse grained models of graphene and graphene oxide for use in aqueous solution

Obtaining stable aqueous dispersions of graphene-based materials is a major obstacle in the development and widespread use of graphene in nanotechnology. The efficacy of atomistic simulations in obtaining a molecular-level insight into aggregation and exfoliation of graphene/graphene oxide (GO) is hindered by length and time scale limitations. In this work, we developed coarse-grained (CG) models of graphene/GO sheets, compatible with the polarizable Martini water model, using molecular dynamics, iterative Boltzmann inversion and umbrella sampling simulations. The new CG models accurately reproduce graphene/GO–water radial distribution functions and sheet–sheet aggregation free energies for small graphene (−316 kJ mol−1) and GO (−108 kJ mol−1) reference sheets. Deprotonation of carboxylic acid functionalities stabilize the exfoliated state by electrostatic repulsion, providing they are present at sufficiently high surface concentration. The simulations also highlight the pivotal role played by entropy in controlling the propensity for aggregation or exfoliation. The CG models improve the computational efficiency of simulations by an order of magnitude and the framework presented is transferrable to sheets of different sizes and oxygen contents. They can now be used to provide fundamental physical insights into the stability of dispersions and controlled self-assembly, underpinning the computational design of graphene-containing nanomaterials.

Ab Initio Molecular Dynamics Investigation of Beryllium Complexes.

Structures of aqueous [Be(H2O)4]2+, its outer-sphere and inner-sphere complexes with F-, Cl-, and SO42-, and dinuclear complexes with a [Be2(κ-OH)(κ-SO4)]+ core have been studied through Car-Parrinello molecular dynamics (CPMD) simulations with the BLYP functional. According to constrained CPMD/BLYP simulations and pointwise thermodynamic integration, the free energy of deprotonation of [Be(H2O)4]2+ and its binding free energy with F- are 9.6 and -6.2 kcal/mol, respectively, in good accord with available experimental data. The computed activation barriers for replacing a water ligand in [Be(H2O)4]2+ with F- and SO42-, 10.9 and 13.6 kcal/mol, respectively, are also in good qualitative agreement with available experimental data. These ligand-substitution reactions are indicated to follow associative interchange mechanisms with backside (SN2-like) attack of the anion relative to the aquo ligand it is displacing. Outperforming static density functional theory computations of the salient kinetic and thermodynamic quantities involving simple polarizable continuum solvent models, CPMD simulations are validated as a promising tool for studying the structures and speciation of beryllium complexes in aqueous solution.

Synthesis of silicon nanoparticles by laser ablation at low fluences in water and ethanol

Colloidal silicon nanoparticles (Si-nc) where synthesized by laser ablation of a solid Si target in water and ethanol. The target was immersed in a vessel containing the solvent and irradiated during 5 and 10 min at different fluences: 0.530, 0.608, 0.687 J cm−2. Ablation was carried out using a laser wavelength of 1064 nm. The obtained colloidal nanoparticles were irradiated after the synthesis to evaluate if laser fragmentation could be produced. In addition, a series of nanoparticles using ethanol as liquid medium was synthesized ablating with 532 nm. Colloidal nanoparticles were structurally characterized by Raman spectroscopy and Transmission Electron Microscopy. Size of the Si-nc were calculated by the theorical models: Bond Polarizability Model (BPM) and One-Phonon Confinement Model (PCM), where nanocrystals ranging from 2 to 11 nm were found.

Understanding Trends in Molecular Bond Angles.

Trends in bond angle are identified in a systematic study of more than a thousand symmetric A2B triatomic molecules. We show that, in series where atoms A and B are each varied within a group, the following trends hold: (1) the A–B–A bond angle decreases for more polarizable central atoms B, and (2) the A–B–A angle increases for more polarizable outer atoms A. The physical underpinning is provided by the extended Debye polarizability model for the chemical bond angle, hence our present findings also serve as validation of this simple classical model. We use experimental bond angles from the literature and, where not available, we optimize molecular geometries with quantum chemical methods, with an open mind with regards to the stability of these molecules. We consider main group elements up to and including the sixth period of the periodic table.

A Polarization-Consistent Model for Alcohols to Predict Solvation Free Energies.

Classical nonpolarizable models, normally based on a combination of Lennard-Jones sites and point charges, are extensively used to model thermodynamic properties of fluids, including solvation. An important shortcoming of these models is that they do not explicitly account for polarization effects, i.e., a description of how the electron density responds to changes in the molecular environment. Instead, polarization is implicitly included, in a mean-field sense, into the parameters of the model, usually by fitting to pure liquid properties (e.g., density). This causes problems when trying to describe thermodynamic properties that involve a change of phase (e.g., enthalpy of vaporization), that directly depend on the electronic response of the medium (e.g., dielectric constant), and that require mixing or solvation in different media (e.g., solvation free energies). Fully polarizable models present a natural route for addressing these limitations but at the price of a much higher computational cost. In this work, we combine the best of those two approaches by running fast simulations using nonpolarizable models and applying post facto corrections to the computed properties in order to account for the effects of polarization. By applying this new paradigm, a new united-atom force field for alcohols is developed that is able to predict both pure liquid properties, including dielectric constant, and solvation free energies in different solvents with a high degree of accuracy. This paves the way for the development of a generic classical nonpolarizable force field that can predict solvation of drug-like molecules in a variety of solvents.

Spectrally Tunable, Large Raman Enhancement from Nonradiative Energy Transfer in the van der Waals Heterostructure

Raman enhancement techniques are essential for fundamental studies in light-matter interactions and find widespread application in microelectronics, bio-chemical sensing, and clinical diagnosis. Two-dimensional (2D) materials and their van der Waals heterostructures (vdWHs) are emerging rapidly as potential platforms for Raman enhancement. Here, we experimentally demonstrate a new technique of Raman enhancement driven by nonradiative energy transfer (NRET) achieving a $10$-fold enhancement in the Raman intensity in a vertical vdWH comprising of a monolayer transition metal dichalcogenide (1L-TMD) placed on a multilayer SnSe\tsub2. Consequently, several weak Raman peaks become visible which are otherwise imperceptible. We also show a strong modulation of the enhancement factor by tuning the spectral overlap between the 1L-TMD and SnSe\tsub2 through temperature variation and the results are in remarkable agreement with a Raman polarizability model capturing the effect of NRET. The observed NRET driven Raman enhancement is a novel mechanism which has not been experimentally demonstrated thus far and is distinct from conventional surface (SERS), tip (TERS) or Interference enhanced Raman scattering (IERS) mechanisms that are driven solely by charge transfer or electric field enhancement. The mechanism can also be used in synergy with plasmonic nanostructures to achieve additional selectivity and sensitivity beyond hot spot engineering for applications like molecular detection using 2D/molecular hybrids. Our results open new avenues for engineering Raman enhancement techniques coupling the advantages of uniform enhancement accessible across a wide junction area in vertical vdWHs.

Coupled cluster theory in the condensed phase within the singles‐T density scheme for the environment response

AbstractReliable simulations of molecules in condensed phase require the combination of an accurate quantum mechanical method for the core region, and a realistic model to describe the interaction with the environment. Additionally, this combination should not significantly increase the computational cost of the calculation compared to the corresponding in vacuo case. In this review, we describe the combination of methods based on coupled cluster (CC) theory with polarizable classical models for the environment. We use the polarizable continuum model (PCM) of solvation to discuss the equations, but we also show how the same theoretical framework can be extended to polarizable force fields. The theory is developed within the perturbation theory energy and singles‐T density (PTES) scheme, where the environmental response is computed with the CC single excitation amplitudes as an approximation for the full one‐particle reduced density. The CC‐PTES combination provides the best compromise between accuracy and computational effort for CC calculations in condensed phase, because it includes the response of the environment to the correlation density at the same computational cost of in vacuo CC. We discuss a number of numerical applications for ground and excited state properties, based on the implementation of CC‐PTES with single and double excitations (CCSD‐PTES), which show the reliability and computational efficiency of the method in reproducing experimental or full‐CC data.This article is characterized under: Electronic Structure Theory > Ab Initio Electronic Structure Methods Electronic Structure Theory > Combined QM/MM Methods Software > Quantum Chemistry

Nafion Ionomer Dispersion in Mixtures of 1‐Propanol and Water Based on the Martini Coarse‐Grained Model

ABSTRACTThe self‐assembly of Nafion ionomer in a mixture of 1‐propanol (NPA) and water was investigated using coarse‐grained molecular dynamics simulations. Ionomer formation into cylindrical bundle‐like aggregates is observed when the ionomer chain size is sufficiently large. The size of ionomer bundles decreases (the diameter decreased from ~2.5 to ~1.9 nm) with increasing NPA content, which indicates that the ionomers tend to be more dispersed at higher NPA content. The results of simulations are in good quantitative agreement with the stable size of an ionomer bundle estimated from our free energy calculations as well as the available experimental data. Furthermore, in contrast to the polarizable NPA model, the standard nonpolarizable NPA model shows the opposite trend that the ionomer size increases with increasing NPA content because of a higher localization of hydronium ions at the bundle surface, revealing that the polarization effect plays a significant role in determining the aggregation behaviors. The present study provides insight into the control of ionomer self‐assembly toward obtaining targeted structures for specific purposes. © 2020 Wiley Periodicals, Inc. J. Polym. Sci. 2020, 58, 487–499

On the physical-chemical nature of solvent polarizability and dipolarity.

The positive solvatochromism of three dyes, with a spectral behavior strongly dependents on the medium dipolarity/polarizability, was studied theoretically. Both a polarizable continuum-solvent model (CSM) and explicit solvent molecules were employed to model solvent effects. The CSM approach, coupled with ten different TDDFT methods, yielded unsatisfactory results in eleven solvents. The explicit-solvation calculations, thought of much higher computational cost, yielded excellent results. As CSM schemes are known correctly model non-specific electrostatic effects, our results indicate that the traditionally considered non-specific nature of solvent dipolarity needs to be reconsidered, requiring the explicit consideration of the solute-solvent interactions for their accurate theoretical description.

Influence of vibrational non-equilibrium on the polarizability and refraction index in air: computational study

Knowledge of optical effects accompanying hypersonic flight conditions is of critical importance to ensure reliable operation of on-board optical instrumentation. This paper presents results of calculations of scalar polarizability dependence on vibrational non-equilibrium in molecular nitrogen and oxygen. The non-equilibrium effects are evaluated on the basis of a semi-classical model for the molecular polarizability. It is shown that, depending on the vibrational and translational populations, changes in the scalar polarizability in excess of normal density and temperature scaling can be around 1%–5% at moderate gas temperatures and around 10% at high temperatures. The model was applied to predict the polarizability for non-equilibrium states in a nitrogen plasma formed by a single nanosecond pulse with different rise times.