ESOL: Estimating Aqueous Solubility Directly from Molecular Structure

Abstract

This paper describes a simple method for estimating the aqueous solubility (ESOL − Estimated SOLubility) of a compound directly from its structure. The model was derived from a set of 2874 measured solubilities using linear regression against nine molecular properties. The most significant parameter was calculated logP_octanol, followed by molecular weight, proportion of heavy atoms in aromatic systems, and number of rotatable bonds. The model performed consistently well across three validation sets, predicting solubilities within a factor of 5−8 of their measured values, and was competitive with the well-established “General Solubility Equation” for medicinal/agrochemical sized molecules.