pH-Switchable Molecularly Imprinted Polymers for Enantioselective Recognition and Separation of (S)-Amlodipine Besylate from its Chiral Counterpart

Abstract

We developed pH-switchable molecularly imprinted polymers (MIPs) for the selective recognition and separation of (S)-amlodipine besylate (S-ADB) in the presence of its chiral enantiomer, (R)-amlodipine besylate (R-ADB) -a challenging task due to their identical molecular composition and high structural similarity. The silica-supported MIPs were fabricated through systematic optimization of synthesis parameters, including functional monomer selection and template ratio, resulting in materials with pH-responsive carboxyl groups that enable reversible binding through protonation-deprotonation transitions. Comprehensive characterization using SEM, FTIR, and TGA confirmed the formation of uniform imprinted layers with excellent thermal stability.The prepared MIPs exhibited remarkable performance characteristics, including rapid adsorption equilibrium attainment (within 1 min) and highly specific recognition (imprinting factor = 6.3). Selectivity tests confirmed that the MIPs demonstrated significantly superior selectivity for S-ADB over structurally similar antihypertensive drugs and notably, its chiral counterpart R-ADB. Systematic binary competitive experiments with S-ADB and R-ADB at varying molar ratios conclusively established the polymer's excellent enantiomeric discrimination capability, showing minimal interference even when the R-ADB concentration was 3 times higher than that of S-ADB-highlighting its efficacy in addressing the key challenge of chiral separation under competitive conditions. The results demonstrate the promising application of pHswitchable MIPs as a novel platform technology for high-precision chiral resolution and pharmaceutical-grade enantiomer purification.