Predicting solvation free energies and thermodynamics in polar solvents and mixtures using a solvation-layer interface condition

Abstract

We demonstrate that with two small modifications, the popular dielectric continuum model is capable of predicting, with high accuracy, ion solvation thermodynamics (Gibbs free energies, entropies, and heat capacities) in numerous polar solvents. We are also able to predict ion solvation free energies in water-co-solvent mixtures over available concentration series. The first modification to the classical dielectric Poisson model is a perturbation of the macroscopic dielectric-flux interface condition at the solute-solvent interface: we add a nonlinear function of the local electric field, giving what we have called a solvation-layer interface condition (SLIC). The second modification is including the microscopic interface potential (static potential) in our model. We show that the resulting model exhibits high accuracy without the need for fitting solute atom radii in a state-dependent fashion. Compared to experimental results in nine water-co-solvent mixtures, SLIC predicts transfer free energies to within 2.5 kJ/mol. The co-solvents include both protic and aprotic species, as well as biologically relevant denaturants such as urea and dimethylformamide. Furthermore, our results indicate that the interface potential is essential to reproduce entropies and heat capacities. These and previous tests of the SLIC model indicate that it is a promising dielectric continuum model for accurate predictions in a wide range of conditions. Published by AIP Publishing. [http://dx.

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

“…Presently, computing the spatially varying φ static ( r ) requires expensive explicit‐solvent simulations or other slow theory, so we have instead adopted a simpler model in which the static potential is constant (uniform) throughout the solute φ static ( r ) = φ static . Depending on the application, the constant should be obtained by either parameterization against experiment , or by explicitly calculating the field at a particular point in an uncharged solute .…”

“…As the charging free energy from λ = 0 to λ = δ is very small compared to the charging free energy over the remaining interval, the charging integral can be approximated as the integral from λ = δ to λ = 1, allowing the use of the familiar linear‐response expression. Readers interested in further details are referred to earlier work . A critical assessment of these approximations is a subject of ongoing work.…”

“…This enhanced model of solvation electrostatics incorporates both the static potential created by solvent structure around the (uncharged) solute van der Waals cavity, and charge‐hydration asymmetry, using a modified boundary condition at the solute interface. We have shown that these two relatively minor changes offer a multitude of benefits for accurate computation of solvation electrostatics . First, we have shown that this model gives accurate charging free energies while using standard MD radii ( R min /2, subject to a single uniform scaling factor for all atom types) .…”

“…That is, the model recovers the correct electrostatic solvation free energy even if one inverts the sign of the charge distribution, without needing to change the atom radii. This property was the original goal of the SLIC model, and it dramatically reduces the number of free parameters in the electrostatic model, from dozens (atomic radii for different atom types) to just five (which depend purely on the solvent) . Beyond the practical advantage of simplifying parameterization procedures, the SLIC model's reduced number of free parameters mean that the model can be parameterized for solvents for which very few reference data are available .…”

“…Fifth, when combined with even a simple solvent‐accessible‐surface‐area (SASA)‐proportional treatment of the nonpolar component of solvation, SLIC is able to predict water‐octanol transfer free energies with an accuracy approaching that of explicit‐solvent MD . Sixth, the model works well for ion solvation in solvent mixtures, as well as ion solvation thermodynamics .…”