COMPARATIVE-EVALUATION OF THE PREDICTIVE POWER OF CALCULATION PROCEDURES FOR MOLECULAR LIPOPHILICITY

The predictive power of four calculation procedures for molecular lipo philicity is checked by comparing with experimental data (log P and ch romatographical R(Mw)) taken from the literature. Two sets of test com pounds are used: the first comprises simple organic molecules and the second consists of more complicated drug molecules. Our comparative ev aluation leads us to conclude that the predictive power is significant ly better for not too complicated organic molecules than for drugs wit h complicated structural pattern. The four investigated calculation pr ocedures should be arranged in two groups with significantly differing predictive power: (a) Rekker and Hansch/Leo and (b) Ghose/Crippen and Suzuki/Kudo. This conclusion is based on a statistical control using log P and R(Mw) as the independent parameters. Correlations have in co mmon: (1) slopes in correlations with calculated data based on fragmen tal methods are not significantly different from 1, calculations with data from atom-based procedures show up in most cases with slopes belo w 1. (2) The accompanying overall statistics underline the superiority of the fragmental methods. We think that all four tested calculation procedures have their own restrictions; for future development we woul d advise a thorough reconsideration of structural effects not fully (o r even not at all) incorporated in the data sets. Special attention wi ll have to be paid to the conformational aspects of lipophilic behavio r.