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.
金属有机骨架材料(MOFs)是一类由金属离子(或金属簇)和有机配体组成的晶体结构化合物。手性MOFs作为一种新型的色谱手性分离材料,已被成功用于拆分手性对映体,表现出良好的手性拆分性能。该研究制备了一种可用于加压毛细管电色谱的手性金属有机骨架修饰毛细管硅胶整体柱。首先,合成了手性金属有机骨架(钴-甘氨酰-L-谷氨酸,Co-L-GG),接着将Co-L-GG作为手性功能单体通过一步原位聚合法制备手性毛细管整体柱。制备手性毛细管整体柱的最佳条件:Co-L-GG用量为5 mg,聚乙二醇用量为0.96 mg,四甲氧基硅烷用量为3.6 mL,甲基三甲氧基硅烷用量为0.4 mL。其次,研究了分离条件对手性药物拆分的影响。在外加电压为-20 kV、流动相为乙腈-20 mmol/L磷酸氢二钠(80∶20, v/v)的条件下,3 min内拆分了6种手性药物,其中氨氯地平、氟伐他汀和色氨酸达到了基线分离。所制备的手性毛细管整体柱表现出良好的重复性和稳定性。最后,使用AutoDock进行分子对接,并借助Discovery Studio对分子对接结果进行分析。结果显示,Co-L-GG与手性药物对映体间的结合自由能差越大,对映体选择性因子越大,然而,这并不一定导致分离度的增加。Co-L-GG中富含伯胺、仲胺和羰基,使其具有对映体识别能力。该研究表明,手性金属有机骨架可用作手性功能单体制备手性毛细管整体柱,在手性化合物的分离和分析中具有广阔的应用前景。
Keywords: chiral metal organic frameworks (CMOF); chiral separation; molecular docking; pressurized capillary electrochromatography (pCEC); recognition mechanism; silica monolithic capillary column.