Equation Theory Of Molecular Liquids Research Articles

Study of the thermodynamic inconsistency of the potential of mean force calculated using the integral equation theory of molecular liquids

In this study, we investigated thermodynamic inconsistency in the potential of mean force (PMF) calculated using the Ornstein-Zernike (OZ), one-dimensional reference interaction site model (1D-RISM), and three-dimensional OZ (3D-OZ) theories. Two methods were used to obtain the PMF: converting the radial distribution function (RDF) into the PMF, and utilizing the solvation free energy (SFE) of the diatomic solute molecule with an added direct interaction between the two solute atoms. Both for the Lennard-Jones (LJ) and Coulomb systems, the hypernetted chain (HNC) closure showed the best performance among the closure relationships tested in this study. However, the performance of the HNC was not perfect and exhibited significant inconsistency in the PMF. The Kovalenko–Hirata and Kobryn–Gusarov–Kovalenko closures were also tested, with fair results when combined with the 1D-RISM equation but poor results when combined with the 3D-OZ equation. The Verlet-modified (VM) closure was found to be inapplicable to Coulomb systems. In contrast, the modified HNC (MHNC) closure showed relatively good results at high temperatures. Furthermore, we modified the Martynov–Sarkisov (MS) closure for Coulomb systems, resulting in a modified MS closure that yields relatively accurate PMF results. We also discuss the behavior of the SFE for Coulomb systems obtained from the 1D-RISM theory, a thorough analysis of both the RDF and the integrand in the Kirkwood charging formula.

Recent developments and applications of reference interaction site model self-consistent field with constrained spatial electron density (RISM-SCF-cSED): A hybrid model of quantum chemistry and integral equation theory of molecular liquids

The significance of solvent effects in electronic structure calculations has long been noted, and various methods have been developed to consider this effect. The reference interaction site model self-consistent field with constrained spatial electron density (RISM-SCF-cSED) is a hybrid model that combines the integral equation theory of molecular liquids with quantum chemistry. This method can consider the statistically convergent solvent distribution at a significantly lower cost than molecular dynamics simulations. Because the RISM theory explicitly considers the solvent structure, it performs well for systems where hydrogen bonds are formed between the solute and solvent molecules, which is a challenge for continuum solvent models. Taking advantage of being founded on the variational principle, theoretical developments have been made in calculating various properties and incorporating electron correlation effects. In this review, we organize the theoretical aspects of RISM-SCF-cSED and its distinctions from other hybrid methods involving integral equation theories. Furthermore, we carefully present its progress in terms of theoretical developments and recent applications.

Computational Analysis of Excited-State Properties of MoS2 Nanosheet Modified with a Pyrene Derivative

MoS2, a representative transition metal dichalcogenides (TMD), is known to undergo the hydrogen evolution reaction in the exfoliated state, and its use as an auxiliary catalyst in place of platinum has been widely reported. Recently, the exfoliation of bulk MoS2 and efficient covalent modification of MoS2 nanosheets with N-bromobenzylmaleimide was successfully achieved using a planetary ball mill. For the photofunctionalization of MoS2, further coupling reaction with a pyrene derivative produced pyrene-benzyl-maleimide-MoS2 (Py-Bn-Mal-MoS2) nanosheet. The absorption spectrum of Py-Bn-Mal-MoS2 shows peaks similar to that of 1-phenylpyrene. On the other hand, the emission spectrum of Py-Bn-Mal-MoS2 is much different from that of 1-phenylpyrene. Furthermore, the emission peak of Py-Bn-Mal-MoS2 is more redshifted with increasing solvent polarity. However, the detailed mechanism is unclear. In this study, we investigated the excited-state properties of Py-Bn-Mal-MoS2 with theoretical methods. First, we constructed model systems of Py-Bn-Mal-MoS2 nanosheet and performed time-dependent density functional theory (TDDFT) calculations. The calculated molecular orbitals and dipole moment changes demonstrated that the emission is a charge transfer transition from the pyrene moiety to MoS2 nanosheet. Next, we performed three-dimensional reference interaction site model (3D-RISM) calculations, which is based on the integral equation theory of molecular liquids, to assess the solvent dependence of emission energies. The calculated results reproduced the experimental solvent dependence well. The distributions of polar solvent molecules showed strong interaction between the excited state of Py-Bn-Mal-MoS2 and solvent molecules. This study supports the potential of covalent modification of MoS2 for photocatalytic applications.

Application of the reference interaction site model self-consistent field method based on the Dirac-Hartree–Fock wave function to a chemical reaction

The reference interaction site model self-consistent field (RISM-SCF) method is a combined method of the electronic structure theory of molecules and the integral equation theory of molecular liquids. The RISM-SCF method based on the Dirac-Hartree-Fock wave function, recently proposed, is applied to a chemical reaction, specifically, a Menshutkin reaction in aqueous solution. The Helmholtz energy profile along the reaction coordinate is calculated and the characteristics of the reaction are discussed based on energy component analysis.

Solvent effects in four-component relativistic electronic structure theory based on the reference interaction-site model.

A combined method of the Dirac-Hartree-Fock (DHF) method and the reference interaction-site model (RISM) theory is reported; this is the initial implementation of the coupling of the four-component relativistic electronic structure theory and an integral equation theory of molecular liquids. In the method, the DHF and RISM equations are solved self-consistently, and therefore the electronic structure of the solute, including relativistic effects, and the solvation structure are determined simultaneously. The formulation is constructed based on the variational principle with respect to the Helmholtz energy, and analytic free energy gradients are also derived using the variational property. The method is applied to the iodine ion (I- ), methyl iodide (CH3 I), and hydrogen chalcogenide (H2 X, where X=O-Po) in aqueous solutions, and the electronic structures of the solutes, as well as the solvation free energies and their component analysis, solvent distributions, and solute-solvent interactions, are discussed.

Recent Developments of Computational Methods for pKa Prediction Based on Electronic Structure Theory with Solvation Models

The protonation/deprotonation reaction is one of the most fundamental processes in solutions and biological systems. Compounds with dissociative functional groups change their charge states by protonation/deprotonation. This change not only significantly alters the physical properties of a compound itself, but also has a profound effect on the surrounding molecules. In this paper, we review our recent developments of the methods for predicting the Ka, the equilibrium constant for protonation reactions or acid dissociation reactions. The pKa, which is a logarithm of Ka, is proportional to the reaction Gibbs energy of the protonation reaction, and the reaction free energy can be determined by electronic structure calculations with solvation models. The charge of the compound changes before and after protonation; therefore, the solvent effect plays an important role in determining the reaction Gibbs energy. Here, we review two solvation models: the continuum model, and the integral equation theory of molecular liquids. Furthermore, the reaction Gibbs energy calculations for the protonation reactions require special attention to the handling of dissociated protons. An efficient method for handling the free energy of dissociated protons will also be reviewed.

Hydration Thermodynamics of Familial Parkinson's Disease-Linked Mutants of α-Synuclein.

The hydration thermodynamics of different mutants of α-synuclein (α-syn) related to familial Parkinson's disease (PD) is explored using a computational approach that combines both molecular dynamics simulations in water and integral equation theory of molecular liquids. This analysis focuses on the change in conformational entropy, hydration free energy (HFE), and partial molar volume of α-syn upon mutation. The results show that A53T, A30P, E46K, and H50Q mutants aggregate more readily and display increased HFE and less negative interaction volume than the wild-type α-syn. In contrast, an opposite trend is observed for the G51D mutant with a lower experimental aggregation rate. The residuewise decomposition analysis of the HFE highlights that the dehydration/hydration of the hydrophilic residue-rich N- and C-termini of α-syn majorly contributes to the change upon mutation. The hydration shell contributions of different residues to the interaction volume are consistent with its increase/decrease upon mutation. This work shows that both HFE and interaction volume determine the aggregation kinetics of α-syn upon mutation and may serve as an appropriate benchmark for the treatment of PD.

Multiscale modeling of active layer of hybrid organic-inorganic solar cells for photovoltaic applications by means of density functional theory and integral equation theory of molecular liquids

Photovoltaic devices convert solar energy into electricity and are promising candidates to reduce carbon emission while providing an alternative way to meet increasing demand in energy consumption. In recent years, organic or hybrid organic-inorganic photovoltaic devices demonstrate steady increase in performance and stability and a promising tendency toward the low production cost. To make them attractive for commercial production, however, a deep understanding and ability to predict physical, chemical and electrochemical processes occurring in photovoltaic conversion layer is needed. Here, we present multiscale modeling of electronic and structural properties of hybrid organic-inorganic perovskites (OIP) of the type CH3NH3PbX3, X = Br, Cl, I, in contact with organic molecules of P3BT, P3HT, or SQ02, including adsorption on inorganic substrates of TiO2. Our methodology is based on Density Functional Theory (DFT) and integral equation theory of molecular liquids in the Reference Interaction Site Model (RISM). We apply it to study the photovoltaic thin film nanomorphology and determine the key factors affecting the performance of OIP-based bulk heterojunction solar cells through their influence on charge separation, charge transport and recombination losses in donor-acceptor blends. These factors include chemical composition of heterojunctions and mutual orientation of molecules on the border of the donor-acceptor or donor-acceptor-substrate systems. Since the formation of thin active layer of solar cells occurs in fluidic phase, we also provide a detailed microscopic insight into the organization of solvent molecules in the solvation shell structure and their contribution to the solvation thermodynamics. In total, these properties define charge transfer processes from donor to acceptor and are utilized in development of new generation organic and hybrid organic-inorganic solar cells. The calculated nanoscale morphologies serve as a guide in rational design of organic or hybrid photovoltaics.

A noniterative mean-field QM/MM-type approach with a linear response approximation toward an efficient free-energy evaluation.

Mean-field treatment of solvent provides an efficient technique to investigate chemical processes in solution in quantum mechanics/molecular mechanics (QM/MM) framework. In the algorithm, an iterative calculation is required to obtain the self-consistency between QM and MM regions, which is a time-consuming step. In the present study, we have proposed a noniterative approach by introducing a linear response approximation (LRA) into the solvation term in the one-electron part of Fock matrix in a hybrid approach between molecular-orbital calculations and a three-dimensional (3D) integral equation theory for molecular liquids (multicenter molecular Ornstein-Zernike self-consistent field [MC-MOZ-SCF]; Kido et al., J. Chem. Phys. 2015, 143, 014103). To save the computational time, we have also developed a fast method to generate electrostatic potential map near solute and the solvation term in Fock matrix, using Fourier transformation (FT) and real spherical harmonics expansion (RSHE). To numerically validate the LRA and FT-RSHE method, we applied the present approach to water, carbonic acid, and their ionic species in aqueous solution. Molecular properties of the solutes were evaluated by the present approach with four different types of initial wave functions and compared with those by the original (MC-MOZ-SCF). We found that an initial wave function considering solvation effects is needed to appropriately reproduce the properties by MC-MOZ-SCF. Furthermore, a benchmark test for 32 solute molecules was performed to evaluate the accuracy of the present approach for solvation free energy (SFE) and measure the speedup ratio for MC-MOZ-SCF. The error of SFE for MC-MOZ-SCF does not correlate with the SFE but increases in proportion to the electronic reorganization energy. Similar to water and carbonic acid, an initial wave function with solvation effects is also important to make the error small. From the averaged speed up ratio, the present approach is 13.5 times faster than MC-MOZ-SCF. © 2019 Wiley Periodicals, Inc.

Organic-Inorganic Nanohybrid Materials for Photovoltaic Applications

Thin film morphology is a key factor determining the performance of bulk heterojunction organic-inorganic solar cells through its influence on charge separation, charge transport and recombination losses in donor-acceptor blends. With this respect, both descriptive and predictive modeling of structural properties of blends of organic-inorganic perovskites of the type CH3NH3PbX3 (X=Cl, Br, or I) with P3HT or P3BT, including adsorption on TiO2 clusters having rutile (110) surface, is presented with the use of a methodo-logy that allows computing the microscopic structure of blends on the nanometer scale. The methodology is based on the integral equation theory of molecular liquids in the reference interaction site model and uses the universal force field. It provides a detailed microscopic insight into the organization of solvent molecules in the solvation shell structure and their contribution to the solvation thermodynamics. The calculated nanoscale morphologies serve as an instrument in rational design of hybrid photovoltaics.

Organic-Inorganic Nanohybrid Materials for Photovoltaic Applications

Thin film morphology is a key factor determining the performance of bulk heterojunction organic solar cells through its influence on charge separation, charge transport and recombination losses in donor-acceptor blends. With this respect, both descriptive and predictive modeling of structural properties of blends of PCBM or organic-inorganic hybrid perovskites of the type CH3NH3PbX3 (X=Cl, Br, I) with P3HT, P3BT or some squaraine SQ2 dye sensitizer, including adsorption on TiO2 clusters having rutile (110) surface, is presented with the use of a methodology that allows computing the microscopic structure of blends on the nanometer scale and getting insight on miscibility of its components at various thermodynamic conditions. The methodology is based on the integral equation theory of molecular liquids in the reference interaction site representation/model (RISM) and uses the universal force field. It is statistical mechanical theory to describe the equilibrium structure of molecular liquids in terms of the site-site pair correlation functions, from which all the thermodynamic quantities can be derived. It provides a detailed microscopic insight into the organization of solvent molecules in the solvation shell structure and their contribution to the solvation thermodynamics. Input parameters for RISM, such as optimized molecular geometries and charge distribution of interaction sites, are derived with the use of the density functional theory (DFT) methods. In particular, the environment effects were taken into account by Conductor-like Screening Model (COSMO) while the charges were obtained by fitting them to reproduce the molecular electrostatic potential (ESP). To compare the diffusivity of the PCBM in binary blends with P3HT and P3BT, respectively, the study is complemented with MD simulation. In addition, the analysis of MD trajectories allows us to better choose the initial positions of molecules in the follow-up DFT analysis which is focused on the study of electronic properties on the border of the perovskite-polymer or perovskite-macromolecule system. These properties define charge transfer processes from donor to acceptor and are utilized in development of new generation organic solar cells. For better understanding, the DFT analysis is also run to study the electronic structure of perovskite surfaces cleaved by (001) and (110) planes. To explore the dependence from the layer thickness we use slabs of different width formed by clusters of unit cells in a slab plain, while to characterize the dependence of electronic structure from layer width we refer to induced partial charges of surface sites (lead and halogens) as well as their electrophilic and nucleophilic Fukui indexes (local softness and hardness), which could be used as quantitative indications for chemical reactivity. As the result of this multiscale modeling approach that includes DFT, RISM, and MD, a remarkably good agreement with available experimental data and results of alternative modeling/simulation is observed for PCBM in P3HT system. We interpret this as a step in validation of the use of our approach for organic photovoltaics and support of its results for new systems that do not have reference data for comparison or calibration. In particular, for the less studied P3BT our results show that expectations about its performance in binary blends with PCBM may be overestimated, as it does not demonstrate the required level of miscibility and short-range structural organization. The RISM model is very sensitive to the blend composition, which happens to be in very good agreement with experimental observations. The inability to find physically meaningful solutions to RISM equations at certain solute concentrations is interpreted as an indicator of the existence of an unstable region on the composition-temperature phase diagram. In case of PCBM in P3BT, the physically meaningful solutions to RISM equations were found for the infinite dilution only, which suggests a much stronger tendency toward phase segregation in PCBM-P3BT blends. This suggestion was confirmed once again in MD simulations that we run (also with the universal force fields) to quickly estimate the diffusion coefficients of PCBM solute in P3HT or P3BT solvents at infinite dilution. Quantitatively, the diffusion coefficients of PCBM in P3HT fall into the range of the ones that are typical for high polymers, while the diffusion coefficients of PCBM in P3BT are closer to the ones that are found for diffusion in fluids. The performance of P3BT with perovskites, however, seems as expected. The calculated nanoscale morphologies of blends of P3HT, P3BT or SQ2 with perovskites, including adsorption on TiO2, are all new and serve as an instrument in rational design of organic/hybrid photovoltaics. They are used in collaboration with experts who actually make prototypes or devices for practical applications.

The Effect of Molecular Structure and Environment on the Miscibility and Diffusivity in Polythiophene-Methanofullerene Bulk Heterojunctions: Theory and Modeling with the RISM Approach.

Although better means to model the properties of bulk heterojunction molecular blends are much needed in the field of organic optoelectronics, only a small subset of methods based on molecular dynamics- and Monte Carlo-based approaches have been hitherto employed to guide or replace empirical characterization and testing. Here, we present the first use of the integral equation theory of molecular liquids in modelling the structural properties of blends of phenyl-C-butyric acid methyl ester (PCBM) with poly(3-hexylthiophene) (P3HT) and a carboxylated poly(3-butylthiophene) (P3BT), respectively. For this, we use the Reference Interaction Site Model (RISM) with the Universal Force Field (UFF) to compute the microscopic structure of blends and obtain insight into the miscibility of its components. Input parameters for RISM, such as optimized molecular geometries and charge distribution of interaction sites, are derived by the Density Functional Theory (DFT) methods. We also run Molecular Dynamics (MD) simulation to compare the diffusivity of the PCBM in binary blends with P3HT and P3BT, respectively. A remarkably good agreement with available experimental data and results of alternative modelling/simulation is observed for PCBM in the P3HT system. We interpret this as a step in the validation of the use of our approach for organic photovoltaics and support of its results for new systems that do not have reference data for comparison or calibration. In particular, for the less-studied P3BT, our results show that expectations about its performance in binary blends with PCBM may be overestimated, as it does not demonstrate the required level of miscibility and short-range structural organization. In addition, the simulated mobility of PCBM in P3BT is somewhat higher than what is expected for polymer blends and falls into a range typical for fluids. The significance of our predictive multi-scale modelling lies in the insights it offers into nanoscale morphology and charge transport behaviour in multi-component organic semiconductor blends.

Partial molar volume of nonionic surfactants in aqueous solution studied by the KB/3D-RISM–KH theory

Description of self-assembly by means of atomistic models without coarse-graining and empirical adjustment is the most challenging problem in statistical mechanics of liquids. Partial molar volume (PMV) is a thermodynamic property related to effective solvation forces spontaneously driving self-assembly of amphiphilic molecules in solution. We calculate the PMV of several ethylene glycol derivatives, in particular, alkyl polyoxyethylene ethers H(CH2)m−1(CH2OCH2)nCH2OH commonly known as CmEn nonionic surfactants, in aqueous solution at infinite dilution by using the Kirkwood–Buff (KB) equation and the three-dimensional reference interaction site model with the Kovalenko–Hirata closure relation (3D-RISM–KH) integral equation theory of molecular liquids. Special attention is paid to the infinite dilution case since direct measurement of PMV of monomeric surfactants is hindered by their very low critical micelle concentration (cmc). The PMVs obtained from the KB/3D-RISM–KH approach are in good qualitative agreement with experimental data for ethylene glycol derivatives in water at 5; 25; and 45°C.

Molecular theory of solvation: Methodology summary and illustrations

Integral equation theory of molecular liquids based on statistical mechanics is quite promising as an essential part of multiscale methodology for chemical and biomolecular nanosystems in solution. Beginning with a molecular interaction potential force field, it uses diagrammatic analysis of the solvation free energy to derive integral equations for correlation functions between molecules in solution in the statistical-mechanical ensemble. The infinite chain of coupled integral equations for many-body correlation functions is reduced to a tractable form for 2- or 3-body correlations by applying the so-called closure relations. Solving these equations produces the solvation structure with accuracy comparable to molecular simulations that have converged but has a critical advantage of readily treating the effects and processes spanning over a large space and slow time scales, by far not feasible for explicit solvent molecular simulations. One of the versions of this formalism, the three-dimensional reference interaction site model (3D-RISM) integral equation complemented with the Kovalenko-Hirata (KH) closure approximation, yields the solvation structure in terms of 3D maps of correlation functions, including density distributions, of solvent interaction sites around a solute (supra)molecule with full consistent account for the effects of chemical functionalities of all species in the solution. The solvation free energy and the subsequent thermodynamics are then obtained at once as a simple integral of the 3D correlation functions by performing thermodynamic integration analytically.

Fast and General Method To Predict the Physicochemical Properties of Druglike Molecules Using the Integral Equation Theory of Molecular Liquids.

We report a method to predict physicochemical properties of druglike molecules using a classical statistical mechanics based solvent model combined with machine learning. The RISM-MOL-INF method introduced here provides an accurate technique to characterize solvation and desolvation processes based on solute-solvent correlation functions computed by the 1D reference interaction site model of the integral equation theory of molecular liquids. These functions can be obtained in a matter of minutes for most small organic and druglike molecules using existing software (RISM-MOL) (Sergiievskyi, V. P.; Hackbusch, W.; Fedorov, M. V. J. Comput. Chem. 2011, 32, 1982-1992). Predictions of caco-2 cell permeability and hydration free energy obtained using the RISM-MOL-INF method are shown to be more accurate than the state-of-the-art tools for benchmark data sets. Due to the importance of solvation and desolvation effects in biological systems, it is anticipated that the RISM-MOL-INF approach will find many applications in biophysical and biomedical property prediction.

A hybrid framework of first principles molecular orbital calculations and a three-dimensional integral equation theory for molecular liquids: multi-center molecular Ornstein-Zernike self-consistent field approach.

In this study, we reported the development of a new quantum mechanics/molecular mechanics (QM/MM)-type framework to describe chemical processes in solution by combining standard molecular-orbital calculations with a three-dimensional formalism of integral equation theory for molecular liquids (multi-center molecular Ornstein-Zernike (MC-MOZ) method). The theoretical procedure is very similar to the 3D-reference interaction site model self-consistent field (RISM-SCF) approach. Since the MC-MOZ method is highly parallelized for computation, the present approach has the potential to be one of the most efficient procedures to treat chemical processes in solution. Benchmark tests to check the validity of this approach were performed for two solute (solute water and formaldehyde) systems and a simple SN2 reaction (Cl(-) + CH3Cl → ClCH3 + Cl(-)) in aqueous solution. The results for solute molecular properties and solvation structures obtained by the present approach were in reasonable agreement with those obtained by other hybrid frameworks and experiments. In particular, the results of the proposed approach are in excellent agreements with those of 3D-RISM-SCF.

Dissipative particle dynamics with an effective pair potential from integral equation theory of molecular liquids.

We present a method of DPD simulation based on a coarse-grained effective pair potential obtained from the DRISM-KH molecular theory of solvation. The theory is first used to calculate the radial distribution functions of all-atom solute monomers in all-atom solvent and then to invert them into an effective pair potential between coarse-grained beads such that their fluid without solvent accounts for molecular specificities and solvation effects in the all-atom system. Bonded interactions are sampled in relatively short MD of the all-atom system and modeled with best multi-Gaussian fit. Replacing the heuristically defined conservative force potential in DPD, the coarse-grained effective pair potential is free from the artificial restrictions on potential range and shape and on equal volume of solute and solvent blobs inherent in standard DPD. The procedure is flexible in specifying coarse-grained mapping and enormously increases computational efficiency by eliminating solvent. The method is validated on polystyrene chains of various length in toluene at finite concentrations for room and polystyrene glass transition temperature. It yields the chain elastic properties and diffusion coefficient in good agreement with experiment and all-atom MD simulations. DPD with coarse-grained effective pair potential is capable of predicting both structural and dynamic properties of polymer solutions and soft matter with high accuracy and computational efficiency.

3D-RISM-Dock: A New Fragment-Based Drug Design Protocol.

We explore a new approach in the rational design of specificity in molecular recognition of small molecules based on statistical-mechanical integral equation theory of molecular liquids in the form of the three-dimensional reference interaction site model with the Kovalenko-Hirata closure (3D-RISM-KH). The numerically stable iterative solution of conventional 3D-RISM equations includes the fragmental decomposition of flexible ligands, which are treated as distinct species in solvent mixtures of arbitrary complexity. The computed density functions for solution (including ligand) molecules are obtained as a set of discrete spatial grids that uniquely describe the continuous solvent-site distribution around the protein solute. Potentials of mean force derived from these distributions define the scoring function interfaced with the AutoDock program for an automated ranking of docked conformations. As a case study in terms of solvent composition, we analyze cooperative interactions encountered in the binding of a flexible thiamine molecule to the prion protein at near-physiological conditions. The predicted location and residency times of computed binding modes are in excellent agreement with the available experimental data.

First-Principles Calculation of the Intrinsic Aqueous Solubility of Crystalline Druglike Molecules

We demonstrate that the intrinsic aqueous solubility of crystalline druglike molecules can be estimated with reasonable accuracy from sublimation free energies calculated using crystal lattice simulations and hydration free energies calculated using the 3D Reference Interaction Site Model (3D-RISM) of the Integral Equation Theory of Molecular Liquids (IET). The solubilities of 25 crystalline druglike molecules taken from different chemical classes are predicted by the model with a correlation coefficient of R = 0.85 and a root mean square error (RMSE) equal to 1.45 log10S units, which is significantly more accurate than results obtained using implicit continuum solvent models. The method is not directly parametrized against experimental solubility data, and it offers a full computational characterization of the thermodynamics of transfer of the drug molecule from crystal phase to gas phase to dilute aqueous solution.

A modified repulsive bridge correction to accurate evaluation of solvation free energy in integral equation theory for molecular liquids

Integral equation theory for molecular liquids is one of the powerful frameworks to evaluate solvation free energy (SFE). Different from molecular simulation methods, the theory computes SFE in an analytical manner. In particular, the correction method proposed by Kovalenko and Hirata [Chem. Phys. Lett. 290, 237 (1998); and J. Chem. Phys. 113, 2793 (2000)] is quite efficient in the accurate evaluation of SFE. However, the application has been limited to aqueous solution systems. In the present study, an improved method is proposed that is applicable to a wide range of solution systems. The SFE of a variety of solute molecules in chloroform and benzene solvents is evaluated. A key is the adequate treatment of excluded volume in SFE calculation. By utilizing the information of chemical bonds in the solvent molecule, the accurate computation of SFE is achieved.