Abstract:

Metal organic frameworks (MOFs) are crystalline compounds composed of metal ions (or metal clusters) and organic ligands. Chiral MOFs have been successfully utilized as novel materials for the separation of chiral enantiomers by chromatography, demonstrating excellent chiral separation performance. In this study, a chiral MOF-modified silica monolithic capillary column was used for pressurized capillary electrochromatography. First, a chiral MOF (Co-glycyl-L-glutamic acid, Co-L-GG) was synthesized. This MOF was then used to prepare a chiral capillary monolithic column via a one-step in situ polymerization method. The optimal conditions for preparing the chiral capillary monolithic column were determined as follows: Co-L-GG amount, 5 mg; polyethylene glycol amount, 0.96 mg; tetramethoxysilane dosage, 3.6 mL; trimethoxymethylsilane dosage, 0.4 mL. Next, the effects of the separation conditions on the separation of chiral drugs were investigated. Under the conditions of an applied voltage of -20 kV and a mobile phase consisting of acetonitrile and 20 mmol/L disodium hydrogen phosphate (80∶20, v/v), six chiral drugs were separated within 3 min, with baseline separation achieved for amlodipine, fluvastatin, and tryptophan. Moreover, the prepared chiral capillary monolithic column exhibited good reproducibility and stability. Finally, molecular docking studies were conducted using AutoDock to explore the chiral recognition mechanism, and the results were analyzed using Discovery Studio. The results indicated that larger differences in binding free energy between Co-L-GG and the enantiomers of the chiral drugs were correlated with higher enantioselectivity factors. However, this correlation did not necessarily lead to an increase in resolution. Co-L-GG, which is enriched with primary amines, secondary amines, and carbonyl groups, demonstrated enantiomeric recognition capability. In conclusion, this study demonstrates that chiral MOFs can be effectively used as chiral functional monomers to prepare chiral monolithic capillary columns, highlighting their significant potential for the separation and analysis of chiral compounds. The comprehensive exploration of the synthesis, characterization, and applications of these MOFs will help provide valuable insights into the development of advanced separation technologies.

Key words: chiral metal organic frameworks (CMOF), silica monolithic capillary column, chiral separation, recognition mechanism, molecular docking, pressurized capillary electrochromatography (pCEC)