Chiral hydroxyl-controlled covalent organic framework-modified stationary phase for chromatographic enantioseparation

Abstract

Chiral covalent organic frameworks (CCOFs) possess a superior chiral recognition environment, abundant pore configuration, and favorable physicochemical stability. In the post-synthetic chiral modification of COFs, research usually focused on increasing the density of chiral sites as much as possible, and little attention has been paid to the influence of the density of chiral sites on the spatial structure and chiral separation performance of CCOFs. In this article, 1,3,5-tris(4-aminophenyl) benzene (TPB), 2,5-dihydroxyterephthalaldehyde (DHTP), and 2,5-dimethoxyterephthalaldehyde (DMTP) served as the platform molecules to directly establish hydroxyl-controlled COFs through Schiff base condensation reactions. Then the novel chiral selectors 6-deoxy-6-[1-(2-aminoethyl)-3-(4-(4-isocyanatobenzyl)phenyl)urea]-β-cyclodextrin (UB-β-CD) were pended into the micropore structures of COFs via covalent bond for further construction the [UB-β-CD]_x-TPB-DMTP COFs (x represents the density of chiral sites). The chiral sites density on [UB-β-CD]_x-TPB-DMTP COFs was regulated by changing the construction proportion of DHTP to obtain a satisfactory CCOFs and significantly improve the ability of chiral separation. [UB-β-CD]_x-TPB-DMTP COFs were coated on the inner wall of a capillary via a covalently bonding strategy. The prepared open tubular capillary exhibited strong and broad enantioselectivity toward a variety of chiral analytes, including sixteen racemic amino acids and six model chiral drugs. By comparing the outcomes of chromatographic separation, we observed that the density of chiral sites in CCOFs was not positively correlated with their enantiomeric separation performance. The mechanism of chiral recognition [UB-β-CD]_x-TPB-DMTP COFs were further demonstrated by molecular docking simulation. This study not only introduces a new high-efficiency member of the COFs-based CSPs family but also demonstrates the enantioseparation potential of CCOFs constructed with traditional post-synthetic modification (PSM) strategy by utilizing the inherent characteristics of porous organic frameworks.

Keywords: Capillary electrochromatography; Chiral covalent organic frameworks; Chiral sites density; Enantioseparation.