Bottom-up synthesis of bridged Bis(β-cyclodextrin)-functionalized chiral COFs@SiO2 for enantioseparation in liquid chromatography.

Chiral covalent organic frameworks (CCOFs) have attracted considerable attention as promising materials for enantioseparation. In this work, a series of β-cyclodextrin-bridged chiral COFs with precisely tunable chiral-site densities were synthesized via a bottom-up strategy using the 1,3,5-tris(4-aminophenyl)benzene (TPB) linkers and newly designed BPTA-CD monomers. The BPTA-CD unit was synthesized by grafting mercapto-β-cyclodextrin (SH-β-CD) onto 2,5-bis(prop‑2-yn-1-yloxy) terephthalaldehyde (BPTA) via a thiol-alkyne "click" reaction. By adjusting the BPTA-CD/BPTA ratio, the density of chiral recognition sites within the COF framework could be finely regulated. The resulting CCOFs were covalently grafted onto silica microspheres to yield COF-grafted silica stationary phases for HPLC enantioseparation. Under optimized conditions, these stationary phases successfully separated 14 out of 19 dansylated amino acids (DNS-AAs) and exhibited high thermal stability and good reproducibility. Increasing the chiral-site density led to markedly enhanced enantioresolution, demonstrating the pivotal role of tunable chiral environments in recognition performance. This work provides an effective strategy for constructing chiral-site-controllable COFs for high-performance liquid chromatographic enantioseparation.