Use of distribution coefficients in quantitative structure-activity relations

Abstract

The use of distribution coefficients (log D) for the analysis of structure-activity relationships of ionizable compounds is described. (D is the ratio of the equilibrium concentration of compound in an organic phase to the total concentration of unionized and ionized species in the aqueous phase at a given pH.) Simpler equations, often with improved correlations, have resulted. This method has the advantage that the influence of pKa or equivalent electronic factors on distribution can be distinguished from electronic effects related to mechanism of action. Several absorption studies are reanalyzed as well as studies on membrane conductance and uncoupling of oxidative phosphorylation.