Separation of chiral drugs through dual chiral ionic liquid functionalized composite membrane and study on chiral recognition mechanism

Abstract

With the increase of demand for single enantiomer drugs, chiral separation methods have been rapidly developed. Benefiting from the characteristics of simple preparation, low equipment requirement, continuous operation and easy scale-up, membrane separation method has great potential in realizing large-scale separation of chiral drugs. In this study, by means of ion exchange, three different amino acids were combined with mono-6-deoxy-6-(3-benzylimidazolium)-β-cyclodextrin ([β-CD-BIM]) to synthesize three dual chiral ionic liquids: [β-CD-BIM][L-Cys], [β-CD-BIM][L-Asp] and [β-CD-BIM][L-Lys]. Then, they were introduced into cellulose acetate membrane by interfacial polymerization to fabricate chiral composite membrane for enantioseparation. In order to improve the separation effect of the composite membrane for chiral molecule, the filtration conditions were investigated and optimized. Under the optimal conditions, for the chiral composite membrane applying [β-CD-BIM][TsO], [β-CD-BIM][L-Cys], [β-CD-BIM][L-Asp] and [β-CD-BIM][L-Lys], the e.e.% of racemic mandelic acid was 33.9%, 47.9%, 31.3% and 60.4% respectively, and the e.e.% obtained for racemic naproxen was 5.5%, 10.3%, 5.7% and 8.7%, individually. Finally, the separation mechanism of different dissociation form for chiral molecule and the recognition mechanism of different chiral ionic liquids were studied by molecular simulation. These findings reveal the excellent enantioseparation performance of prepared chiral membrane, providing a new perspective on the design of chiral membranes.