Chiral Covalent Organic Framework Composite CCOF‐301@SiO ₂ for Multi‐Mode HPLC Enantiomeric Separation

Chiral covalent organic frameworks (CCOFs) show great potential for chromatographic separation, due to their abundant chiral recognition sites and unique structures. A novel CCOF core-shell composite, CCOF-301@SiO₂, was constructed by post-synthesis modification (PSM) and in-situ growth strategies, and the effect of the amount of acetic acid catalyst on the synthesis of CCOF-301@SiO₂ core-shell microspheres was discussed. The prepared CCOF-301@SiO₂ microspheres composite was used as a multifunctional chiral stationary phase (CSP) for HPLC enantiomeric separation under normal-phase (NP) and reversed-phase (RP) modes. The experimental results showed that the CCOF-301@SiO₂ column exhibited excellent separation performance, with 20 chiral compounds being separated in NP mode and 12 chiral compounds in RP mode, including alcohols, esters, ketones, and amines. Compared with the commercially available Chiralpak AD-H column, the CCOF-301@SiO₂ column exhibited good complementarity in enantiomeric separation performance. In addition, the effects of analyte mass, column temperature, and mobile phase composition on the separation were investigated. Good repeatability and stability of the CCOF-301@SiO₂ column for enantioseparation were observed. This study demonstrates that the CCOFs@SiO₂ constructed by PSM and in-situ growth strategies have great potential as an HPLC stationary phase.