van der Waals Volume and the Related Parameters for Hydrophobicity in Structure-Activity Studies

Abstract

The correlations of Hansch’s hydrophobic constant (log P) with van der Waals volume (Vw) and with van der Waals surface area (Aw) were studied using 60 molecules including apolar organic compounds and inert gases, and superiority of Vw over Aw was recognized. From the obtained highly significant relation of Vw to log P and a great number of log P values for polar molecules, hydrophilic effects (VH) of various polar groups were evaluated. These parameters (Vw and VH) could be satisfactorily applied to the regression analysis of water-solubility of 156 organic liquids and frog muscle narcosis of 39 drugs. These parameters may especially be useful for drug design because they can easily be calculated for a wide variety of molecules. © 1976, The Pharmaceutical Society of Japan. All rights reserved.