Here’s a nice example of the application of computed solvation energies in non-aqueous studies. Cramer and Truhlar have employed their latest SM8 technique, which is parameterized for organic solvents and for water, to estimate solvation energies in olive oil.1 Now you may wonder why solvation in olive oil of all things? But the partitioning of molecules between water and olive oil has been shown to be a good predictor of lipophilicity and therefore bioavailability of drugs! The model works reasonably well in reproducing experimental solvation energies and partition coefficients. They do make the case that fluorine substitution which appears to improve solubility in organics,originates not to more favorable solvation in organic solvents (like olive oil) but rather that fluorine substitution dramatically decreases solubility in water.


(1) Chamberlin, A. C.; Levitt, D. G.; Cramer, C. J.; Truhlar, D. G., "Modeling Free Energies of Solvation in Olive Oil," Mol. Pharmaceutics, 2008, 5, 1064-1079, DOI: 10.1021/mp800059u