Solvation thermodynamics of neutral and charged solutes using the solvation‐layer interface condition continuum dielectric model

Abstract

We demonstrate that the solvation-layer interface condition (SLIC) continuum dielectric model for molecular electrostatics, combined with a simple solvent-accessible-surface-area (SASA)-proportional model for nonpolar solvent effects, accurately predicts solvation entropies of neutral and charged small molecules. The SLIC/SASA model has only seven fitting parameters in total and achieves this accuracy using a training set with only 20 compounds. Despite this simplicity, solvation free energies and entropies are nearly as accurate as those predicted by the more sophisticated Langevin dipoles solvation model. Surprisingly, the model automatically reproduces the negligible contribution of electrostatics to the solvation of hydrophobic compounds.Opportunities for improvement include nonpolar solvation, anion solvation entropies, and heat capacities. More molecular realism may be needed for these quantities. To enable a future, explicit-solvent-based assessment of the SLIC/SASA implicit-solvent model, we predict solvation entropies for the Mobley test set, which are available as Supporting Information.

Solv: An Alternative Continuum Model Implementation Based on Fixed Atomic Charges, Scaled Particle Theory, and the Atom–Atom Potential Method

“…These obstacles spurred the development of computationally cheap implicit solvation models in which the solvent is described as a dielectric. Over the last few decades, a number of dielectric continuum models − have been suggested: various flows of the polarizable continuum model (PCM), , Poisson–Boltzmann model, and generalized Born solvation model SM12; conductor-like solvation model (COSMO) , and its extension to real solvents (COSMO-RS and COSMO-SAC); linear scaling domain decomposition PCM (ddPCM) and COSMO (ddCOSMO) , approaches of Stamm and co-workers with their adjustment for quantum mechanical, semiempirical, and force field methods; , solvation model based on density (SMD); composite method for implicit representation of solvent (CMIRS); − self-consistent continuum solvation (SCCS), , easy solvation energy (ESE), extended easy solvation estimation (xESE), easy solvation estimation using PM7 charges (ESE-PM7), and universal easy solvation evaluation (uESE) approaches; solvation-layer interface condition continuum dielectric model for molecular electrostatics; the charge-asymmetric nonlocally determined local-electric solvation model; generalized finite-difference Poisson–Boltzmann approach in the CRYSTAL code; , and multiscale solvation-layer interface condition continuum model to name a few. Finally, the performance of continuum models is often enhanced through the introduction of a few explicit solvent molecules around the solvent opening, the so-called hybrid or cluster-continuum approach that is reviewed elsewhere. − …”

Energy-Scaled Debye–Hückel Theory for the Electrostatic Solvation Free Energy in Size-Asymmetric Electrolyte Solutions

“…Solvation in solutions is a fundamental process in physical chemistry, biochemistry, and solution chemistry. The solvation thermodynamics has important implications in understanding the salt effect, − surface tension of electrolyte solutions, − self-assembly at surfaces, , protein crystallization, , protein folding, , ligand binding, , stability of colloidal suspensions, − and structure of electric double layers. − An important thermodynamic property of solvation is the solvation free energy, also called excess chemical potential μ ex . The solvation free energy μ ex can be split into a cavity formation energy μ cav , a van der Waals (vdw) solvation energy μ vdw , and an electrostatic solvation free energy (ESFE) μ e .…”

Inclusion of Water Multipoles into the Implicit Solvation Framework Leads to Accuracy Gains

“…The electrostatic effects ,− are described by the electrostatic part of the total solvation free energy, Δ G el , which is often the most time-consuming computation in practical models. Accurate estimates of the total solvation energy, Δ G solv , and especially its change upon conformational transitions, require an accurate estimate of the nonpolar part, ,− Δ G np . Coupling between Δ G el and Δ G np , currently neglected by most practical implicit solvent models, can also be important − when high levels of accuracy are required.…”