A deep eutectic solvent-assisted green synthesis of advanced three-dimensional covalent organic framework based stationary phase for dual-mode liquid chromatography.

Two-dimensional covalent organic frameworks (2D COFs) are widely used as stationary phases in liquid chromatography, yet their simple pore structures often mandate surface modifications to attain the necessary separation selectivity. In contrast, three-dimensional COFs (3D COFs) feature customizable hierarchical channel systems with complex pore structures, high specific surface areas, and spatially diversified active sites, enabling superior separation selectivity and enhanced column efficiency. Furthermore, their rigid frameworks prevent structural collapse of stationary phase, offering unique advantages for advanced separations. Therefore, the development of innovative 3D COF@silica stationary phase represents a promising strategy that leverages the established benefits of silica supports while incorporating the tunable porosity and functionality of 3D COFs. This work presents an eco-friendly deep eutectic solvent-mediated synthesis of an imine-linked 3D-Azo-TFPM-COF@silica stationary phase, which eliminates hazardous solvents and reduces reaction time. The synthesized material demonstrated excellent chromatographic performance in separating polar compounds and positional isomers. Meanwhile, the 3D-Azo-TFPM-COF@silica column was applied to cosmetic analysis for quantifying nicotinamide content in commercial whitening essences with high accuracy (recovery: 95.82-102.92%) and good precision (RSD < 0.4%). This work presents a straightforward and green synthetic approach for 3D COF based stationary phases, broadening their application in chromatographic separations and demonstrating their potential for advanced analytical techniques.