Estimation of Molecular Linear Free Energy Relation Descriptors Using a Group Contribution Approach

Abstract

Additive models for the estimation of Abraham's molecular descriptors R 2, π 2 H, Σα 2 H, Σβ 2 H, Σβ 2 O, and log L 16 have been developed. For five of the six descriptors, one set of 81 atom and functional group fragments is capable of reproducing experimentally derived results with correlation coefficients ranging from 0.95 to 0.99. However, one descriptor, Σα 2 H, required an entirely separate set of 51 fragments to be developed, resulting in a correlation coefficient of 0.97. Of particular importance is the speed of calculation (approximately 700 molecules/min), allowing so-called “high-throughput screening”. Several applications of this model for molecules containing intramolecular interactions are discussed.