Lipophilicity measurements of benzenesulfonamide inhibitors of carbonic anhydrase by reversed-phase HPLC

Abstract

The lipophilicity of 33 meta and para substituted benzenesulfonamides has been studied by reversed-phase high-performance liquid chromatography (RPLC) using methanol/water or acetonitrile/water as the mobile phases and μ-bondapak C 18 as the stationary phase. A linear relationship between the capacity factor (log k′) and the volume fraction of the organic modifier (φ) has been established for each solute. The extrapolation of the retention to φ = 0 (0% of organic modifier) permitted the elimination of any selective and specific effects of organic modifier, to calculate log k w and finally to derive τ w for each substituent. The Hansch's π hydrophobic parameter was linearly correlated to τ w ( r = 0.953), but no improvement in the correlation equation was observed when τ w values obtained by adding silanol masking amines to the mobile phase were used. By introducing an indicator variable which takes into account the possibility of the substituent to make hydrogen bondings, a slight but significant improvement was instead observed. The replacement of π with τ w in the regression equation obtained in our recent quantitative structure-activity relationship (QSAR) study on carbonic anhydrase inhibition by benzenesulfonamides gives rise to a correlation equation with comparable statistical significance.