Methods

Before presenting a brief review of the various procedures for calculating log P, it is well to clear up some confusion in labeling and nomenclature used in the past. The "atom-based" methods must take into account the number and types of bonds to surrounding atoms, i.e. their environment. Thus "atom-centered fragments" is a more accurate designation, and it takes over 100 (and preferably over 250) of them to adequately handle a data file of moderate size and complexity. At least one method using molecular properties derived from quantum chemical theory claims a sharp contrast to the methods employing fragments of substituents "which have no scientific basis" [29]. However, the parameters derived from molecular orbital (MO) calculation must first be validated through regression analysis and then they work well only when combined with indicator variables. There can be no doubt of the desirability of calculating log P from molecular properties, rather than from the summation of parts, but that requires knowledge of the solvent-directed forces which influence conformation, hydrogen bonding, tautomeric equilibria, etc.

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