Chiral covalent organic framework core-shell composite CTpBD@SiO2 used as stationary phase for HPLC enantioseparation

The fascinating framework structures and unique properties of chiral covalent organic frameworks (COFs) make them promising candidates as novel separation medium for high-performance liquid chromatography (HPLC). However, the irregular morphology, inhomogeneous particle size, and low density of conventional COF particles will lead to a low column efficiency, undesirable chromatographic peak shape, and high column backpressure of such COF-packed columns. In this work, a chiral COF CTpBD was synthesized by the Schiff base reaction between benzidine (BD) and chiral organic monomer CTp obtained through the reaction of 1,3,5-triformylphoroglucinol (Tp) and (+)-diacetyl-L-tartaric anhydride ((+)-Ac-L-Ta). The chiral COF CTpBD was immobilized on the surface of amino functionalized silica (SiO2-NH2) by an in situ growth approach to prepare the chiral COF core-shell microsphere composite CTpBD@SiO2, which was used as a novel chiral stationary phase (CSP) for HPLC enantioseparation. Various kinds of racemates were separated on the CTpBD@SiO2-packed column with a low column backpressure (8–11 bar). Some effects such as the analyte mass and column temperature on the HPLC enantioseparation have been studied in detail. The fabricated CTpBD@SiO2-packed column exhibited high column efficiency (e.g., 16,800 plates m−1 for atenolol), high enantioselectivity, and good reproducibility toward various racemates. The highest resolution value, retention factor, and separation factor reach to 2.11, 2.85, and 3.73, respectively. The relative standard deviations (RSD) of peak area, peak height, half-peak width, and retention time of atenolol were all below 3.0%.Graphical abstract