In situ preparation of chiral-induced covalent organic framework stationary phase for enantioseparation of drugs.

BACKGROUND: In open-tubular capillary electrochromatography (OT-CEC), the trade-off between chiral recognition ability and loading capacity remains a major bottleneck for the development of chiral stationary phases (CSPs). Traditional CSPs are plagued by uneven distribution of chiral selectors, discontinuous structures, poor mechanical stability and low column efficiency. Covalent organic frameworks (COFs) possess large specific surface areas and abundant porous structures, making them ideal carriers for chiral selectors. Nevertheless, the size mismatch between chiral selectors and COFs pores, conformational changes of chiral reagents during preparation, as well as the complicated fabrication procedures of chiral COFs, severely restrict their applications in chiral separation.

RESULTS: A novel chiral-induced COF (Λ)-TpPa-Py was in-situ grown on quartz capillaries under mild conditions to fabricate high-performance CSPs for enantioseparation. The coating achieved a good balance between chiral selectivity and loading capacity. Characterizations verified successful synthesis and stable immobilization of (Λ)-TpPa-Py. The column realized baseline separation of six chiral drugs with resolution (Rs) ranging from 1.50 to 2.72, and showed excellent repeatability (RSD < 5.40%) and long-term stability. Molecular docking and adsorption kinetics indicated that hydrogen bonding, π-π stacking, hydrophobic and π-sigma interactions jointly droved chiral recognition.

SIGNIFICANCE: This work introduces chiral-induced COF into CSPs for OT-CEC, addressing the issues of complex preparation procedures and poor stability of traditional CSPs. Furthermore, this in-situ fabrication strategy for chiral-induced COF provides a facile and scalable route to high-performance CSPs. It also broadens the enantioseparation scope of chiral-induced COF-based stationary phases, showing great potential for practical separation of chiral drugs. Notably, the (Λ)-TpPa-Py@column exhibited insufficient resolution for a small number of weakly interacting chiral analytes, which restricts its wider practical application scope.