Simultaneous determination of acid dissociation constants and true partition coefficients by analyses of the apparent partition coefficients. I.

Abstract

Since the partition coefficient P and the dissociation constant pKa are important in studies of structure-activity relationships, the pH dependence of the apparent partition coefficient Pa was quantitatively studied for the cases of acids and bases. Linear relations for mono-acids and mono-bases, but parabolic relations for the dissociation of two functional groups in the pH region studied were derived between Pa and proton concentration. The equations, however, are different for acids and bases. These equations make it possible to determine pKa and the log P simultaneously. Some experimental systems have been measured and compared with the results obtained by other techniques ; the agreement was good. A consideration of the dissociation in the organic phase showed that the correction factor due to ionic dissociation in the organic phase for an octanolbuffer system is negligible in the pH region near the pKa value, but is not negligible in the general equation connecting the Pa and P values.