Continuum Solvation Model Research Articles

Performance of molecular dynamics simulation for predicting of solvation free energy of neutral solutes in methanol

Abstract In this study, molecular dynamics simulation was applied for calculating solvation free energy of 16 solute molecules in methanol solvent. The thermodynamic integration method was used because it was possible to calculate the difference in free energy in any thermodynamic path. After comparing results for solvation free energy in different force fields, COMPASS force field was selected since it had the lowest error compared to experimental result. Group-based summation method was used to compute electrostatic and van der Waals forces at 298.15 K and 1 atm. The results of solvation free energy were obtained from molecular dynamics simulation and were compared to the results from Solvation Model Density (SMD) and Universal Continuum Solvation Model (denoted as SM8), which were obtained from other research works. Average square-root-error for molecular dynamics simulation, SMD and SM8 models were 0.096091, 0.595798, and 0.70649. Furthermore, the coefficient of determination (R 2) for molecular dynamics simulation was 0.9618, which shows higher accuracy of MD simulation for calculating solvation free energy comparing to two other models.

Improved prediction of solvation free energies by machine-learning polarizable continuum solvation model

Theoretical estimation of solvation free energy by continuum solvation models, as a standard approach in computational chemistry, is extensively applied by a broad range of scientific disciplines. Nevertheless, the current widely accepted solvation models are either inaccurate in reproducing experimentally determined solvation free energies or require a number of macroscopic observables which are not always readily available. In the present study, we develop and introduce the Machine-Learning Polarizable Continuum solvation Model (ML-PCM) for a substantial improvement of the predictability of solvation free energy. The performance and reliability of the developed models are validated through a rigorous and demanding validation procedure. The ML-PCM models developed in the present study improve the accuracy of widely accepted continuum solvation models by almost one order of magnitude with almost no additional computational costs. A freely available software is developed and provided for a straightforward implementation of the new approach.

Toward a First-Principles Framework for Predicting Collective Properties of Electrolytes

Given the universal importance of electrolyte solutions, it is natural to expect that we have a nearly complete understanding of the fundamental properties of these solutions (e.g., the chemical potential) and that we can therefore explain, predict, and control the phenomena occurring in them. In fact, reality falls short of these expectations. But, recent advances in the simulation and modeling of electrolyte solutions indicate that it should soon be possible to make progress toward these goals. In this Account, we will discuss the use of first-principles interaction potentials based in quantum mechanics (QM) to enhance our understanding of electrolyte solutions. Specifically, we will focus on the use of quantum density functional theory (DFT) combined with molecular dynamics simulation (DFT-MD) as the foundation for our approach. The overarching concept is to understand and accurately reproduce the balance between local or short-ranged (SR) structural details and long-range (LR) correlations, allowing the prediction of the thermodynamics of both single ions in solution as well as the collective interactions characterized by activity/osmotic coefficients. In doing so, relevant collective motions and driving forces characterized by chemical potentials can be determined.In this Account, we will make the case that understanding electrolyte solutions requires a faithful QM representation of the SR nature of the ion-ion, ion-water, and water-water interactions. However, the number of molecules that is required for collective behavior makes the direct application of high-level QM methods that contain the best SR physics untenable, making methods that balance accuracy and efficiency a practical goal. Alternatives such as continuum solvent models (CSMs) and empirically based classical molecular dynamics have been extensively employed to resolve this problem but without yet overcoming the fundamental issue of SR accuracy. We will demonstrate that accurately describing the SR interaction is imperative for predicting both intrinsic properties, namely, at infinite dilution, and collective properties of electrolyte solutions.DFT has played an important role in our understanding of condensed phase systems, e.g., bulk liquid water, the air-water interface, ions in bulk, and at the air-water interface. This approach holds huge promise to provide benchmark calculations of electrolyte solution properties that will allow for the development and improvement of more efficient methods, as well as an enhanced understanding of fundamental phenomena. However, the standard protocol using the generalized gradient approximation with van der Waals (vdW) correction requires improvement in order to achieve a high level of quantitative accuracy. Simply simulating with higher level DFT functionals may not be the best route considering the significant computational cost. Alternative methods of incorporating information from higher levels of QM should be explored; e.g., using force matching techniques on small clusters, where high level benchmark calculations are possible, to develop ideal correction terms to the DFT functional is a promising possibility. We argue that DFT with statistical mechanics is becoming an increasingly useful framework enabling the prediction of collective electrolyte properties.

Fullerene–phosphorene–nanoflake nanostructures: Modulation of their interaction mechanisms and electronic properties through the size of carbon fullerenes

In this work, we employed density functional theory modeling to obtain the structure, binding mechanism, and electronic/optical properties of carbon-based interfaces formed by phosphorene nanoflakes and carbon fullerenes (C24 to C70). Fullerenes form stable covalent and non-covalent complexes with phosphorene depending on their molecular size. A continuum solvation model indicates that complexes are stable in solution, independent of the solvent polarity. Two classes of covalent complexes arise by cycloaddition-like reactions (nanobuds): the first class, where short-range effects (charge-transfer and polarization) determine the stability; the second one, where short-range effects decay to avoid steric repulsion, and long-range forces (electrostatics and dispersion) favors the stability. High-size fullerenes (C50–C70) only form non-covalent complexes as experimentally obtained due to strong repulsion at shorter intermolecular distances and lack of dissociation barriers. Fullerenes also act as mild p-dopants for phosphorene, increasing its polar character and ability to acquire induced dipole moments. Moreover, small energy-bandgap (low-size) fullerenes increase the phosphorene metallic character. Fullerenes also act as active sites for orbital-controlled interactions and maximize the phosphorene light absorbance at the UV–Vis region. An outlook of these nanostructures provides practical nanotechnological applications in storage, batteries, sensing, bandgap engineering, and optoelectronics.

DFT Analysis of Organotin Catalytic Mechanisms in Dehydration Esterification Reactions for Terephthalic Acid and 2,2,4,4-Tetramethyl-1,3-cyclobutanediol.

Polyesters synthesized from 2,2,4,4-tetramethyl-1,3-cyclobutanediol (TMCD) and terephthalic acid (TPA) are improved alternatives to toxic polycarbonates based on bisphenol A. In this work, we use ωB97X-D/LANL2DZdp calculations, in the presence of a benzaldehyde polarizable continuum model solvent, to show that esterification of TMCD and TPA will reduce and subsequently dehydrate a dimethyl tin oxide catalyst, becoming ligands on the now four-coordinate complex. This reaction then proceeds most plausibly by an intramolecular acyl-transfer mechanism from the tin complex, aided by a coordinated proton donor such as hydronium. These findings are a key first step in understanding polyester synthesis and avoiding undesirable side reactions during production.

Contribution of Solvents to Geometrical Preference in the Z/E Equilibrium of N-Phenylthioacetamide.

We studied the Z/E preference of N-phenylthioacetamide (thioacetanilide) derivatives in various solvents by means of 1H NMR spectroscopy, as well as molecular dynamics (MD) and other computational analyses. Our experimental results indicate that the Z/E isomer preference of secondary (NH)thioamides of N-phenylthioacetamides shows substantial solvent dependency, whereas the corresponding amides do not show solvent dependency of the Z/E isomer ratios. Detailed study of the solvent effects based on molecular dynamics simulations revealed that there are two main modes of hydrogen (H)-bond formation between solvent and (NH)thioacetamide, which influence the Z/E isomer preference of (NH)thioamides. DFT calculations of NH-thioamide in the presence of one or two explicit solvent molecules in the continuum solvent model can effectively mimic the solvation by multiple solvent molecules surrounding the thioamide in MD simulations and shed light on the precise nature of the interactions between thioamide and solvent. Orbital interaction analysis showed that, counterintuitively, the Z/E preference of NH-thioacetamides is mainly determined by steric repulsion, while that of sterically congested N-methylthioacetamides is mainly determined by thioamide conjugation.

Amino Acid Interactions (INTAA) web server v2.0: a single service for computation of energetics and conservation in biomolecular 3D structures.

Interactions among amino acid residues are the principal contributor to the stability of the three-dimensional structure of a protein. The Amino Acid Interactions (INTAA) web server (https://bioinfo.uochb.cas.cz/INTAA/) has established itself as a unique computational resource, which enables users to calculate the contribution of individual residues in a biomolecular structure to its total energy using a molecular mechanical scoring function. In this update, we describe major additions to the web server which help solidify its position as a robust, comprehensive resource for biomolecular structure analysis. Importantly, a new continuum solvation model was introduced, allowing more accurate representation of electrostatic interactions in aqueous media. In addition, a low-overhead pipeline for the estimation of evolutionary conservation in protein chains has been added. New visualization options were introduced as well, allowing users to easily switch between and interrelate the energetic and evolutionary views of the investigated structures.

TD-DFT assessment of UV-vis spectra palladium and platinum complexes with thiols and disulfides.

Time-dependent density functional theory (TD-DFT) and spectrophotometric methods were used for speciation analysis in systems disulfides (cystine, cystamine, homocystine, 3,3-dithiodipropionic acid) - [PdCl4]2- or [PtCl4]2-. We use the M06-2X and CAM-B3LYP density functionals with Def2-SVP basis set to reproduce the experimental UV-vis spectra; the polarized continuum solvation model (PCM) was fitted to take into account solvation effects of the medium (water). Used methods have shown the good agrees with the experiment - theoretical values of transition energies differ from real parameters within ±0.15eV for functional CAM-B3LYP. Binuclear disulfide complexes of Pd(II) with cystine and cystamine have form S,N-coordination sites, instead of S,S-conformation. It was shown that Pd(II)thiolate complexes formed by cleavage of the disulfide bond exist as [PdCl3L] and [Pd2S2L2]. Pt(II)-disulfide systems have confirmed the presence of [Pt2Cl6(R-SS-R)] and [PtCl4(S-R)] complex species. The DFT/CAM-B3LYP/Def2-SVP/SMD level can be recommended for theoretical estimations of absorption spectra of complexes of palladium or platinum and sulfur-containing ligands.

Solvation free energy of the proton in acetonitrile

Solvation free energy of the proton in solution is used to describe proton transfer processes in that solution. In addition, the solvation free energy of the proton is involved in several chemical and biological processes. Although several methodological approaches have been used to estimate the solvation free energy of the proton in solutions (mainly in water), there is no consensus estimate of the solvation free energy of the proton. In this work, we have reported the solvation free energy of the proton in acetonitrile using the cluster continuum solvation model. To compute the solvation free energy of the proton within this model, one needs the structures of neutral and protonated acetonitrile clusters. Thus, we thoroughly explored the potential energy surfaces (PESs) of the clusters in the solvent phase using several incremental levels of theory. We generated initial structures using classical molecular dynamics. Then the generated structures have been successively optimized at the MN15/6-31++G(d,p) and MP2/aug-cc-pVDZ levels of theory. Finally, single point extrapolations to the complete basis set (CBS) limit have been performed at the MP2 level of theory. As results, the solvation free energy (respectively enthalpy) of the proton in acetonitrile is estimated to be −1022.0 kJmol−1 (respectively −1056.5 kJmol−1) at the MP2/CBS level of theory. The calculated solvation free energy of the proton in acetonitrile is found to be in excellent agreement with the experimental estimate based on the tetraphenylarsonium-tetraphenylborate (TATB) approach.

Experimental and Theoretical Characterization of Ultrafast Water-Soluble Photochromic Photoacids.

UV-visible transient absorption spectroscopy and quantum mechanical simulations are combined to elucidate the photochemical mechanism of two metastable merocyanine/spiropyran photoacids, 2-[(E)-2-(2-hydroxyphenyl)ethenyl]-3,3-dimethyl-1-(3-sulfopropyl)-3H-indol-1-ium (phenylhydroxy-MCH) and 2-[(E)-2-(1H-indazol-7-yl)ethenyl]-3-(3-sulfopropyl)-1,3-benzothiazol-3-ium (indazole-MCH). Transient absorption spectra demonstrate that trans-acid isomerization to the cis form results in deprotonation on a picosecond time scale. Ring closure to form spiropyran follows promptly from the appropriate conformation or follows at longer time delays (≫3.5 ns) following a barrier crossing for single-bond isomerization to the appropriate conformation. Consistent with the results of Berton et al. [ Chem. Sci. 2020, 11, 8457-8468] , we find that cis-phenylhydroxy-MCH is a stronger acid than trans-phenylhydroxy-MCH. The decrease in pKa upon isomerization is further investigated to benchmark quantum chemical methods for their accuracy. Calculations were performed with nine levels of theory including continuum solvent models and explicit water. The calculations are not sufficient to describe the ΔpKa following isomerization of these photoacids, and more work is necessary to properly evaluate the physical basis for the acidity of the cis photoacids.

Modeling Complex Solvent Effects on the Optical Rotation of Chiral Molecules: A Combined Molecular Dynamics and Density Functional Theory Study.

The challenge of assigning the absolute stereochemical configuration to a chiral compound can be overcome via accurate ab initio predictions of optical rotation, a sensitive molecular property that is further complicated by solvent effects. The solvent's "chiral imprint"-the transfer of the chirality from the solute to the surrounding achiral solvent-is explored here using conformational averaging and time-dependent density-functional theory. These complex solvent effects are taken into account via simple averaging over a molecular dynamics trajectory together with the explicit quantum mechanical consideration of the solvent molecules within the solute's cybotactic region and implicit modeling of the bulk solvent. We consider several axes along which the system's optical rotation varies, including the sampling of the dynamical trajectory, the quality of the one-electron basis set, and the use of continuum solvent models to account for bulk effects.

Catalytic Urea Synthesis from Ammonium Carbamate Using a Copper(II) Complex: A Combined Experimental and Theoretical Study.

The synthesis of urea fertilizer is currently the largest CO2 conversion process by volume in the industry. In this process, ammonium carbamate is an intermediate en route to urea formation. We determined that the tetraammineaquacopper(II) sulfate complex, [Cu(NH3)4(OH2)]SO4, catalyzed the formation of urea from ammonium carbamate in an aqueous solution. A urea yield of up to 18 ± 6% was obtained at 120 °C after 15 h and in a high-pressure metal reactor. No significant urea formed without the catalyst. The urea product was characterized by Fourier transform infrared (FT-IR), powder X-ray diffraction (PXRD), and quantitative 1H{13C} NMR analyses. The [Cu(NH3)4(OH2)]SO4 catalyst was then recovered at the end of the reaction in a 29% recovery yield, as verified by FT-IR, PXRD, and quantitative UV-vis spectroscopy. A precipitation method using CO2 was developed to recover and reuse 66 ± 3% of Cu(II). The catalysis mechanism was investigated by the density functional theory at the B3LYP/6-31G** level with an SMD continuum solvent model. We determined that the [Cu(NH3)4]2+ complex is likely an effective catalyst structure. The study of the catalysis mechanism suggests that the coordinated carbamate with [Cu(NH3)4]2+ is likely the starting point of the catalyzed reaction, and carbamic acid can be involved as a transient intermediate that facilitates the removal of an OH group. Our work has paved the way for the rational design of catalysts for urea synthesis from the greenhouse gas CO2.

Thermally activated delayed fluorescence: A critical assessment of environmental effects on the singlet-triplet energy gap.

The effective design of dyes optimized for thermally activated delayed fluorescence (TADF) requires the precise control of two tiny energies: the singlet-triplet gap, which has to be maintained within thermal energy, and the strength of spin-orbit coupling. A subtle interplay among low-energy excited states having dominant charge-transfer and local character then governs TADF efficiency, making models for environmental effects both crucial and challenging. The main message of this paper is a warning to the community of chemists, physicists, and material scientists working in the field: the adiabatic approximation implicitly imposed to the treatment of fast environmental degrees of freedom in quantum-classical and continuum solvation models leads to uncontrolled results. Several approximation schemes were proposed to mitigate the issue, but we underline that the adiabatic approximation to fast solvation is inadequate and cannot be improved; rather, it must be abandoned in favor of an antiadiabatic approach.

Potential-Dependent Mechanistic Study of Ethanol Electro-oxidation on Palladium.

We herein used the density functional theory (DFT) method and the implicit continuum solvation model to study the potential-dependent mechanism of ethanol oxidation reaction (EOR) on palladium (Pd). Energy evolutions of the EOR on low-index Pd surfaces, including (111), (110), and (100), were obtained as a function of the electrode potential. Moreover, the onset potentials for key intermediates and products were calculated. In addition, the potential range for adsorbed ethanol as the most stable adsorption state for proceeding the EOR was determined to be between 0.15 and 0.78 V via the calculated Pourbaix diagrams when considering hydrogen underpotential deposition and Pd(II) oxide formation as competing reactions. Specifically, the behavior of Pd(111) as the dominating facet decided the overall activity of the EOR with onset potentials to acidic acid/acetate at 0.40 V, to carbon dioxide at 0.71 V, and to oxide formation at 0.78 V. Pd(110) was predicted to exhibit the optimal activity toward the EOR with the lowest onset potentials to both the first dehydrogenation process and carbon dioxide at 0.08 and 0.60 V, respectively. A computational potential-dependent mechanism of the EOR was proposed, which agrees well with the experimental curve of linear sweeping voltammetry on the commercial Pd/C electrocatalyst. Our study suggests that targeted control of products can be tuned with proper overpotential and thus provides a foundation for the future development of EOR electrocatalysts.

Efficient Photogeneration of Hydrogen Boosted by Long-Lived Dye-Modified Ir(III) Photosensitizers and Polyoxometalate Catalyst

Efficient Photogeneration of Hydrogen Boosted by Long-Lived Dye-Modified Ir(III) Photosensitizers and Polyoxometalate Catalyst

A Density Functional Theory Study of Optical Rotation in Some Aziridine and Oxirane Derivatives.

We present time-dependent density functional theory (TDDFT) calculations of the electronic optical rotation (ORP) for seven oxirane and two aziridine derivatives in the gas phase and in solution and compare the results with the available experimental values. For seven of the studied molecules it is the first time that their optical rotation was studied theoretically and we have therefore investigated the influence of several settings in the TDDFT calculations on the results. This includes the choice of the one-electron basis set, the exchange-correlation functional or the particular polarizable continuum model (PCM). We can confirm that polarized quadruple zeta basis sets augmented with diffuse functions are necessary for converged results and find that the aug-pc-3 basis set is a viable alternative to the frequently employed aug-cc-pVQZ basis set. Based on our study, we cannot recommend the generalized gradient functional KT3 for calculations of the ORP in these compounds, whereas the hybrid functional PBE0 gives results quite similar to the long-range correct CAM-B3LYP functional. Finally, we observe large differences in the solvent effects predicted by the integral equation formalism of PCM and the SMD variant of PCM. For the majority of solute/solvent combinations in this study, we find that the SMD model in combination with the PBE0 functional and the aug-pc-3 basis set gives the best agreement with the experimental values.

Basis Set Selection for Calculation of Structural and Electronic Properties of Systems Incorporating a Superoxide Radical in an Aqueous Medium

In this work, computer simulation has been carried out, and the molecular parameters of oxygen and a superoxide ion have been calculated to select the most optimal basis set of functions for further quantum mechanical calculations that include the presence of reactive oxygen species. For each particle, the equilibrium bond lengths and averaged polarizabilities in a continuous dielectric aqueous medium are obtained with the Conductor-like Polarizable Continuum Model (CPCM) and Solvation Model based on Density (SMD). Calculations for the 16 basic sets are conducted using the Orca software package. The obtained numerical values are compared with experimental data. The electron affinity energy of the oxygen molecule is used as the main selection criterion. The total time of computer calculations for each basis set is considered, and the most optimal basis sets are selected. The basis sets 6-31+G(d), 6-311+G, def2-TZVPD, and aug-cc-pVDZ are recommended for numerical calculations of molecular systems incorporating molecular oxygen and superoxide radical as its reduction product.

Energy change mechanisms of HMX solute molecules in pure solvents and binary solvent mixtures

The quantum mechanical continuum solvation models have been used to probe into the energy change mechanisms of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) solute molecules in pure solvents and binary solvent mixtures. The relation between the long-range electrostatic energy and the static dielectric constant is determined by the integral equation-formalism polarizable continuum model (IEFPCM). For solvents having hydrogen bonds, the electrostatic interaction is significantly high due to the short-range polarization induced by solute-solvent hydrogen bonding that is unfavorable to crystallization from solution. The non-electrostatic energy has been calculated by the universal solvation model (SMD), which arises from the effects of cavitation, dispersion, and solvent structure (CDS). The calculated interaction energies from different components are discussed in terms of the solvent descriptors, temperature and molecular geometries. The simulation results show that the effects of CDS are important to antisolvent crystallization in dimethyl sulfoxide (DMSO)-alcohol binary solvent mixtures and the energy change mainly originates from the short-range non-electrostatic interaction.

Phosphonate Chelators for Medicinal Metal Ions.

A family of phosphonate-bearing chelators was synthesized to study their potential in metal-based (radio)pharmaceuticals. Three ligands (H6phospa, H6dipedpa, H6eppy; structures illustrated in manuscript) were fully characterized, including X-ray crystallographic structures of H6phospa and H6dipedpa. NMR spectroscopy techniques were used to confirm the complexation of each ligand with selected trivalent metal ions. These methods were particularly useful in discerning structural information for Sc3+ and La3+ complexes. Solution studies were conducted to evaluate the complex stability of 15 metal complexes. As a general trend, H6phospa was noted to form the most stable complexes, and H6eppy associated with the least stable complexes. Moreover, In3+ complexes were determined to be the most stable, and complexes with La3+ were the least stable, across all metals. Density functional theory (DFT) was employed to calculate structures of H6phospa and H6dipedpa complexes with La3+ and Sc3+. A comparison of experimental 1H NMR spectra with calculated 1H NMR spectra using DFT-optimized structures was used as a method of structure validation. It was noted that theoretical NMR spectra were very sensitive to a number of variables, such as ligand configuration, protonation state, and the number/orientation of explicit water molecules. In general, the inclusion of an explicit second shell of water molecules qualitatively improved the agreement between theoretical and experimental NMR spectra versus a polarizable continuum solvent model alone. Formation constants were also calculated from DFT results using potential-energy optimized structures. Strong dependence of molecular free energies on explicit water molecule number, water molecule configuration, and protonation state was observed, highlighting the need for dynamic data in accurate first-principles calculations of metal-ligand stability constants.

Efficient Quantum Chemical Calculation of Structure Ensembles and Free Energies for Nonrigid Molecules.

The application of quantum chemical, automatic multilevel modeling workflows for the determination of thermodynamic (e.g., conformation equilibria, partition coefficients, pKa values) and spectroscopic properties of relatively large, nonrigid molecules in solution is described. Key points are the computation of rather complete structure (conformer) ensembles with extremely fast but still reasonable GFN2-xTB or GFN-FF semiempirical methods in the CREST searching approach and subsequent refinement at a recently developed, accurate r2SCAN-3c DFT composite level. Solvation effects are included in all steps by accurate continuum solvation models (ALPB, (D)COSMO-RS). Consistent inclusion of thermostatistical contributions in the framework of the modified rigid-rotor-harmonic-oscillator approximation (mRRHO) based on xTB/FF computed PES is also recommended.