The efficiency of RP-TLC for lipophilicity assessment. A comparative study on a series of pyrrolyl-acetic acid derivatives, inhibitors of aldose reductase

Abstract

The lipophilicity of a series of pyrrolyl-acetic acid derivatives, inhibitors of the aldose reductase enzyme, was assessed by reversedphase thin layer chromatography (RP-TLC). The role of the carbon content of the stationary phase in reproducing the octanol-water partitioning was examined using RP-18 F254S and RP-8 F254S plates. Retention on RP-8 plates was found to be more uniform, while these plates exhibit some advantages for the lipophilicity assessment of acidic compounds, compared to the most commonly used RP-18 plates. However, in both cases, different energetics between octanol-water partitioning and RP-TLC retention seem to be involved. On both plates the influence of ionization of the acid functional group was found to be more pronounced on retention in comparison with previous findings for basic compounds. Both sets of R Mw values were compared with HPLC chromatographic indices, reported previously. They were found to correlate better with logk w values, if the latter have been determined in the presence of noctanol as mobile phase additive. In all cases, best relationships were obtained with R Mw(C18). The performance of R Mw indices in regression equations modeling the aldose reductase inhibitory activity was evaluated. Results were comparable with those previously generated using logP. Both R Mw(C8) and R Mw(C18) proved to perform equally well as lipophilicity indices in correlating biological activity, if combined with the ionization correction term Q and Abraham's basicity term B as additional parameters. © Akadémiai Kiadó, Budapest