Predicting Accurate Solvation Free Energy in n‑Octanol Using 3D-RISM-KH Molecular Theory of Solvation: Making Right Choices

Molecular theory of solvation, a.k.a., three-dimensional reference interaction site model theory of solvation with Kovalenko–Hirata closure relation (3D-RISM-KH), is an accurate and fast theory predicting solvation free energy and structure. Here we report a benchmark study of n-octanol solvation free energy calculations using this theory. The choice of correct force field parameters is quintessential for the success of 3D-RISM theory, and we present a guideline to obtain them for n-octanol solvent. Our best prediction of the solvation free energy on a set of 205 small organic molecules supplemented with the so-called “universal correction” scheme yields relative mean unsigned error of 0.94 kcal/mol against the reported database. The best agreement is obtained with the united atom (UA) type force field parametrization of n-octanol with the van der Waals parameters of hydroxyl hydrogen reported by Kobryn et al. [Kobryn, A. E.; Kovalenko, A. J. Chem. Phys. 2008, 129, 134701].