Steric and lipophobic components of the hydrophobic fragmental constant

Abstract

Newly calculated increments of molar volumes and surface areas were compared with hydrophobic fragmental constants in an effort to establish a relationship between these parameters. For completely non-polar fragments, the hydrophobicity is directly and linearly related to the volume or surface area. In the case of most fragments, however, the hydrophobicity is found to result from two factors, namely, a) a volume- or surface-related lipophilicity, and b) a lipophobicity effect, designated. The physical meaning of this parameter is unclear at present and may be related to hydration effects. The parameter may be of interest in QSAR studies. This is illustrated by an example in which the combined use of V and discriminates between the steric and lipophobic contributions of the partition coefficient to the biological activity.