Evaluation of the predictive power of calculation procedure for molecular hydrophobicity of some estradiol derivates

Several calculation procedures for log P values based on the fragmental and atomic contributions are compared with experimental reversed-phase liquid chromatography (RPLC) retention of estradiol derivates. The RPLC experiments were performed on HPTLC and HPLC commercially available stationary phases. Binary solvent mixtures of methanol-water and acetonitrile-water were used as mobile phases. The correlation between log P and various chromatographically obtained hydrophobicity parameters (R-m(o), log k(w), and phi(0)) are quantified. The R-m(o), i.e., log k(w) were obtained by linear extrapolation of retention to 0% organic modifier. phi(0) values were obtained from the slopes and intercepts of such linear relationship. The mutual relationship between phi(0,MeOH) and phi(0,ACN) values of the compounds were discussed. The obtained statistical results can be summarized in the following order of reliabilities for different log P calculation methods: Broto>ACD/>logP>Crippen> Rekker>Viswanadhan. (C) 2002 Elsevier Science B.V. All rights reserved.