Enantioseparation of warfarin derivatives on molecularly imprinted polymers for (S)- and (R)-chlorowarfarin

Monodisperse molecularly imprinted polymers (MIPs) for warfarin (WF), 4'-chlorowarfarin (CWF), (S)-CWF and (R)-CWF (MIPWF, MIPCWF, MIP(S)-CWF and MIP(R)-CWF, respectively) were prepared using 4-vinylpyridine (4-VPY) and ethylene glycol dimethacrylate (EDMA) as a functional monomer and a crosslinker, respectively, by multi-step swelling and polymerization. The molar ratio of a template molecule, 4-VPY to EDMA was 6:18:25 or 4:18:25. The retention and molecular recognition properties of MIPWF and MIPCWF were evaluated using a mixture of sodium phosphate buffer or ammonium formate and acetonitrile in reversed-phase LC. WF and CWF on these MIPs gave the maximal retentions at mobile phase pH 7, and those retentions were decreased with an increase of acetonitrile content. The retention and imprinting factors were in the order of WF < CWF < 4'-bromowarfarin (BWF) on MIPWF and MIPCWF in neutral mobile phases. On the other hands, in acidic mobile phases the retention factors were in the same order with those in neutral mobile phases, while the imprinting factors of WF and CWF were higher on the respective MIPs. These results suggest that ionic or hydrogen bonding interactions, hydrophobic interactions and pi-pi interactions could work for the retention and molecular recognition of WF, CWF and BWF on these MIPs in a reversed-phase mode. Furthermore, MIP(S)-CWF and MIP(R)-CWF could separate WF, CWF and BWF enantiomers in acidic mobile phases. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

Monodisperse molecularly imprinted polymers were prepared for warfarin and its derivatives, showing good retention and molecular recognition properties in liquid chromatography. The molecular interactions responsible for the retention and recognition of these compounds on the polymers were discussed, indicating potential applications in chiral separation.