A surface area approach to determination of partition coefficients

Abstract

A suite of computer programs (AMBER, MS, SURFACE, and GENSTAT) has been used to calculate the contribution to surface area by the component atoms of a large number of benzene derivatives containing a variety of substituents such as alkyl, hydroxy, alkoxy, amino, and carbonyl functions (ester, ketone, and aldehyde). We have also considered a wide range of polyaromatic compounds. Component surface areas were related to the measured n-octanol–water partition coefficients (P) of the molecules under consideration, using linear regression analysis. This surface area group contribution approach was then used to estimate the partition coefficient of other molecules, the structures of which could be defined in terms of the components that have been used in the current model for predicting log P.