Hydrophobic properties of anticonvulsant phenylacetanilides. Relationship between octanol-water partition coefficient and capacity factor determined by reversed-phase liquid chromatography.

Abstract

Partition coefficients (octanol-water), P, for a series of phenylacetanilides, PhCH2CONHC6H4-Xm,p, were determined by the shaking-flask method. The observed .pi. values (.pi. = log P(I)-log PPhCH2CONHPh) were analyzed in terms of substituent effects to give the relationship .pi. = 0.833.pi.x +0.788.sigma.x + 0.040, where .pi.x = logPhx - logPhH. The capacity factors for these compounds, k'', which are regarded as an alternative hydrophobic parameter, were determined and analyzed by using reversed-phase high-performance liquid chromatography (RP-HPLC) in different H2O-organic solvent mixtures. The substituent effects on the log k'' value were influenced by the organic modifier in the mobile phase. Linear relationships between log P and log k'' were generally observed but there were some outliers such as OH, CN and NO2 derivatives. The deviation of phenolic compounds from the log P-log k'' linearity can be explained in terms of the difference in partitioning behavior between the octanol-water system and the lipophilic stationary phase-mobile phase system.