Estimation of Hydrophobicity Based on the Solvent-Accessible Surface Area of Molecules

Abstract

A novel method of estimating Hansch's hydrophobic constant (logP) by making use of the solvent-accessible surface area (SA) with correction for the hydrophilic effect of any polar moiety (SH) is proposed. The correlation coefficient (r) between observed and estimated values of log P was 0.995 with 138 miscellaneous compounds. The method can reproduce the differences of logP among geometrical isomers. Such differences are not calculable by using other available methods. An application of SAand SHto the regression analysis of water-solubility data of 156 different organic liquids gave r = 0.981. The proposed method may offer new insight into the physico-chemical nature of hydrophobic phenomena. © 1985, The Pharmaceutical Society of Japan. All rights reserved.