Glutathione-functionalized covalent organic frameworks@silica as a hydrophilic-hydrophobic balanced mixed-mode stationary phase for highly efficient separation of compounds with a wide range of polarity

Background Covalent organic frameworks (COFs) are a highly promising stationary phase for high-performance liquid chromatography (HPLC), but the separation of polar compounds is limited by their low hydrophilicity. Therefore, it is crucial to develop novel COFs-based stationary phases with balanced hydrophilicity-hydrophobicity for the efficient separation of different polar compounds. Results In this paper, glutathione (GSH)-functionalized COFs@silica microspheres (GSH-COFs@SiO 2 ) were synthesized via a two-step, post-synthesis modification strategy. The COFs particles was constructed onto silica surface by the covalent conjugation of 1,3,5-tris(4-aminophenyl)benzene and 2,5-divinylterephthalaldehyde. GSH containing abundant –NH 2 and –COOH groups was bonded onto the surface of COFs@SiO 2 to further enhance hydrophilicity. The resulting GSH-COFs@SiO 2 exhibited balanced hydrophilicity-hydrophobicity and can be used in hydrophilic/reversed-phase liquid chromatography modes through multiple retention mechanisms. Consequently, a variety of compounds with different polarity, including nucleosides/bases, benzoic acids, anilines, phenols, alkylbenzenes and polycyclic aromatic hydrocarbons, were well separated with ideal resolution, satisfactory column efficiency and good peak shapes. Furthermore, this novel column exhibited remarkable column stability, as evidenced by intra-day relative standard deviations of 0.08 %–0.18 % for retention time and 0.45 %–1.47 % for peak area. Significance and novelty This work demonstrates the superior hydrophilic-hydrophobic selectivity of GSH-COFs@SiO 2 stationary phases towards compounds with a wide range of polarity and provides a very facile and easily popularized post-synthetic modification route for hydrophilic-hydrophobic balanced COFs-based HPLC stationary phases.