Liposome-cyclodextrin synergistic system for enhanced chiral separation of Fmoc-amino acid enantiomers in capillary electrophoresis.

A micro-nano structure enhanced chiral separation strategy is proposed by integrating biomimetic liposome assemblies with cyclodextrin (CD) derivatives as composite chiral selectors in capillary electrophoresis (CE). The self-assembly of weakly chiral, poorly soluble phospholipids into liposomes markedly amplifies chiral discrimination when coupled with CD-based molecular recognition, enabling highly efficient separation of multiple 9-fluorenylmethoxycarbonyl (Fmoc)-amino acid enantiomers. This enhancement is proposed to be associated with the formation of interfacial pre-enrichment microzones on liposome surfaces, where locally concentrated selectors and analytes may engage in synergistic hydrogen bonding, hydrophobic interactions, and steric effects, collectively strengthening chiral recognition. The composite system exhibits good selectivity and compatibility in mixed-sample separations, supporting simultaneous enantioseparation of multiple amino acids with high reproducibility. Beyond establishing an effective CE-based approach for amino acid enantiomer separation, this work demonstrates a proof-of-concept for transforming poorly soluble, weakly chiral substances into efficient chiral selectors through micro-nano assembly, offering preliminary insights for synergistic chiral separation systems.