Hydrophobicity Parameters Determined by Reversed-Phase Liquid Chromatography. X. Relationship between Capacity Factor and Octanol-Water Partition Coefficients of Monosubstituted Thiophenes.

Abstract

Capacity factors, k', of monosubstituted thiophenes were obtained by reversed-phase high-performance liquid chromatography, using three kinds of octadecyl silica (ODS) columns and methanol-buffer (pH 7.4) eluents. The relationship between log k' and log P (P : octanol-water partition coefficient) was analyzed in terms of the H-bonding properties of the substituents as a function of the mobile phase composition. Non-hydrogen-bonders and H-acceptors gave a good linear log k'-log P relationship in the eluent containing 50% methanol. As the methanol content was decreased, ester substituents, which are strong H-acceptors, deviated from the regression line. Amide groups, amphiprotic substituents, behaved differently from the non-amphiprotics, as is usually observed. The log kw approach (log kw; the extrapolated log k' value in water) correctly predicted the log P value for non-hydrogen-bonders and weak H-acceptors such as H, alkyls, halogens and OMe, but over-estimated log P for the others. The H-bonding effect of the thiophene ring seems to be small, and hence, the retention behavior of thiophene derivatives is considered to be mainly dependent upon the H-bonding property of substituents.