A linear solvation energy relationship analysis of selected imidazoline derivatives in reversed-phase thin-layer chromatography

Abstract

A linear solvation energy relationship (LSER) analysis of 19 selected imidazoline derivatives was performed using retention data obtained from four different thin-layer chromatography (TLC) systems with the same mobile phase consisting of methanol‒water‒ammonia and with different polarities of the stationary phase (CN, RP2, RP8, and RP18). Stepwise multiple linear regression and partial least square regression were applied to examine the most significant Abraham’s descriptors affecting retention under the investigated conditions. The results obtained showed that the Abraham descriptors with the most significant contribution to the retention mechanism in all studied TLC systems were molecular volume (V) and solute basicity (B), with V having a positive influence and B a negative influence on retention. All models created met very strict internal and external validation criteria, indicating their high reliability in predicting the retention behavior of compounds containing the imidazoline scaffold. Furthermore, correlation studies between retention data and pharmacokinetic properties, such as volume of distribution, rate of brain penetration, and blood‒brain partition coefficient revealed the potential of the examined reversed-phase systems as an alternative biomimetic tool for the rapid profiling of novel imidazoline analogs