ESOL: Estimating Aqueous Solubility Directly from Molecular Structure

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
logPoctanol, 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.