Optimization of solute cavities and van der Waals parameters in ab initio MST‐SCRF calculations of neutral molecules

The cavity used to represent the solute/water interface in Miertus–Scrocco–Tomasi self‐consistent reaction field (MST‐SCRF) calculations of neutral molecules has been optimized by fitting to experimental data. The study is focused on the refinement of the van der Waals radii of polar and apolar hydrogens and of the van der Waals parameters used to compute the dispersion/repulsion contribution to the total free energy of hydration. When a scaling coefficient of 1.25 is used to build the solute cavity, comparison of 6‐31G*/MST results with experimental data demonstrates that the optimum van der Waals radii for hydrogens are around 1.2 Å (apolar) and 0.9 Å (polar). The optimization of the solute cavity and the refinement of the van der Waals parameters lead to root mean square deviations in the computed free energy of hydration of only 0.9 kcal/mol for the 23 molecules considered in this study.