Chiral Ionic Covalent Organic Framework Core-Shell Composite Material CD-COF-Li@SiO₂ for HPLC Enantioseparation

Ionic covalent organic frameworks (iCOFs), as a branch of emerging organic framework materials, integrate charged functional sites with periodically ordered pore structures. Owing to their distinctive merits, including adjustable electrostatic interactions, permanent porosity, well-defined pore channels, and excellent structural designability, iCOFs have aroused widespread research interest. In this study, a novel HPLC chiral stationary phase (CD-COF-Li@SiO₂) was prepared by an in situ growth strategy. The CD-COF-Li@SiO₂ column showed good chiral separation performance for 19 pairs of enantiomers, including alcohols, esters, ketones, organic acids, and aldehydes. Most of the analytes were baseline-separated, and the resolution of some enantiomers (1-(4-chlorophenyl) ethanol and 2-chloro-2-phenylacetophenone) reached 3.00. Compared with CTpBD@SiO₂, β-CD-COF@SiO₂, and two widely used commercial chiral columns (Chiralpak AD-H and Chiralcel OD-H), it was found that the fabricated column had good chiral recognition complementarity with four chiral chromatographic columns. Furthermore, the effects of the injection mass of the analyte, column temperature, and the proportion of the mobile phase on the separation of racemates were also discussed. This column exhibited good reproducibility and stability. After hundreds of injections, the relative standard deviation (RSD) values of retention time and resolution were both below 1%. In addition, the proposed CD-COF-Li@SiO₂-based HPLC method demonstrated favorable performance for quantitative analysis by using (S)-ethyl mandelate as a model analyte. Accordingly, the limit of detection value of 0.38 µg·mL^-1 and the limit of quantitation value of 1.26 µg·mL^-1 for (S)-ethyl mandelate detection were obtained. This work highlights the promising prospects of chiral iCOFs for enantioseparation in HPLC.