Reversed-phase thin-layer chromatographic and computational evaluation of lipophilicity parameters of α,β-unsaturated acids

Abstract

The retention behavior of 10 previously synthesized α,β-unsaturated acids that exhibited antimicrobial activity was studied using 12 reversed-phase thin-layer chromatography (RP-TLC) systems. The mobile phases consisted of three solvent combinations (methanol‒water, acetonitrile‒water, and acetone‒water) in four different ratios (50:50, 60:40, 70:30, and 80:20, V/V). The chromatographic parameters ${R}_{M}^{0}$, a, and C₀ were calculated for each system. The lipophilicity parameters of the tested compounds were predicted using various computational methods. The acetone‒water system demonstrated the highest correlation coefficients between the chromatographic and calculated lipophilicity parameters, which makes it the most suitable for evaluating the lipophilicity of the tested compounds. This system successfully reflected the effect of the lipophilic properties of the compounds on their retention behavior. To elucidate the retention mechanisms, the molecular properties of the tested compounds were calculated and a genetic algorithm was used to identify the properties with the greatest influence on the retention behavior. The interpretation of these descriptors revealed structural and physicochemical properties crucial for the behavior of the tested compounds. In addition, the pharmacokinetic properties of the compounds were estimated using in silico methods. The observed correlation between the retention mechanism and physicochemical properties affecting membrane transport and physiological binding ability highlights the applicability of RP-TLC conditions for rapid profiling of newly synthesized α,β-unsaturated acids.