Construction of chiral crown ethers into robust covalent organic frameworks for electrochromatographic enantioseparation

Abstract

Capillary electrochromatography (CEC) is a rapidly emerging separation technique that merges the high separation efficiency of capillary electrophoresis with the exceptional selectivity of liquid chromatography. However, it remains a synthetic challenge to design functional chiral stationary phases (CSPs) with high chemical stability against acid and base in CEC enantioseparation. Here we demonstrate that incorporating chiral crown ethers into stable covalent organic frameworks (COFs) enable efficient and stable separations of racemates by CEC. This facilitates us to craft two three-dimensional chiral COFs (CCOFs) by polycondensation of a chiral 1,1'-binaphyl-20-crown-6-derived dialdehyde and tetraamines with diisopropyl substituents. Both feature a 11-fold interpenetrated diamond framework, characterized by tubular open channels decorated with chiral crown ethers serving as enantioselective recognition and binding sites. These frameworks demonstrate excellent stability in water, acid, and base, thanks to the presence of bulky iso-propyl groups that shield the dynamic imine linkages. Moreover, the precisely defined COF channels enhanced the accessibility of the enclosed crown ethers to the analytes while providing strong protection against harsh environments, rendering them suitable for CSPs in CEC separations. They can effectively separate some important enantiomers, including ketones, epoxides, and alkaline substances, when utilized as coatings on chiral columns, particularly facilitating the chiral separation of drugs. This study advances the application of COFs in electrochromatographic separations, expanding the scope of porous materials design and engineering to create COFs with targeted enantioselective properties.