Facile construction of a multifunctional β-cyclodextrin functionalized COF stationary phase for versatile HPLC applications

Covalent organic frameworks (COFs), featuring well-defined porosity, high surface area and tunable functionality, are promising materials for chromatographic separation. However, when directly used as stationary phases in HPLC, pristine COF-silica composites often exhibit inherent limitations, including excessive hydrophobicity and limited separation selectivity. To address these challenges, employing high-surface-area COF as a structural platform followed by targeted functionalization offers an effective solution. β-Cyclodextrin (β-CD), characterized by its unique cavity structure and multiple chiral centers, features hydrophobic inner edges and hydrophilic outer edges. This distinctive architecture enables β-CD to selectively form host-guest inclusion complexes with solutes, showcasing significant potential for enantiomeric separation. The integration of COF with β-CD synergistically combines their complementary advantages, establishing a versatile platform for simultaneous chiral and achiral separations. In this study, a β-CD-modified COF stationary phase (β-CD-TpBD-COF@Silica) was synthesized, employing β-CD as the chiral selector and imine-based TpBD-COF as the substrate. The β-CD facilitates stereoselective recognition via its intrinsic chiral cavity, while the TpBD-COF provides a robust immobilization platform for β-CD and synergistically enhances separation. The resulting β-CD-TpBD-COF@Silica composite integrates multiple separation mechanisms, such as hydrophobicity, hydrogen bonding and π-π interactions, to achieve multimodal separation, successfully separating hydrophobic analytes (alkylbenzenes, phenyl ketones), hydrophilic compounds (nucleosides, sulfonamides), and chiral molecules. Notably, the β-CD-TpBD-COF@Silica column exhibits outstanding repeatability and separation efficiency, achieving baseline resolutions of all analytes within 8 min, demonstrating robust chromatographic performance and operational stability. Furthermore, the β-CD-TpBD-COF@Silica column was applied to detect sulfonamides in milk, highlighting its practicality for real-world analysis. This work presents a rational design strategy for multifunctional COF-based stationary phases, offering enhanced selectivity for complex separation tasks.