Revisiting the Use of Quantum Chemical Calculations in LogP_{octanol-water} Prediction

Abstract

The partition coefficients of drug and drug-like molecules between an aqueous and organic phase are an important property for developing new therapeutics. The predictive power of computational methods is used extensively to predict partition coefficients of molecules. The application of quantum chemical calculations is used to develop methods to develop structure–activity relationship models for such prediction, either based on molecular fragment methods, or via direct calculation of solvation free energy in solvent continuum. The applicability, merits, and shortcomings of these developments are revisited here.

Keywords

• octanol-water partition coefficients
• quantum chemical calculations
• ab initio methods
• density functional theory
• continuum solvation models
• reference interaction site model