Estimation of lipophilicity and retention behavior of some alpha adrenergic and imidazoline receptor ligands using rp-tlc

Abstract

The chromatographic behavior of 16 alpha adrenergic and imidazoline receptor ligands has been studied by reversed-phase thin-layer chromatography (RP-TLC) on RP-18 and CN stationary phases. Retention constant R-M(0) was determined for all tested compounds in three different chromatographic systems: methanol-water/RP-18, tetrahydrofuran-ammonia-water/RP-18, and tetrahydrofuran-ammonia-water/CN. Good correlations between determined hydrophobic parameters R-M(0) and calculated log P values were obtained for the system tetrahydrofuran-ammonia-water on both RP-18 and CN stationary phases. Experimentally obtained R-M(0) values and computed molecular parameters of the examined compounds were further used for the quantitative structure-retention relationship (QSRR) study, in order to determine the most important properties governing retention. The QSRR modeling was performed with use of the partial least squares regression, and predictive performances of the developed QSRR models were tested by use of the cross-validation and external test set prediction. The created models revealed that apart from lipophilicity, constitutional descriptors, the amount of van der Waals surface area having a property P (P_VSA-like descriptors), and hydrogen bonding properties of the tested compounds were important for the retention behavior in the RP-TLC systems.