Crystal morphology tuning and green post-synthetic modification of metal organic framework for HPLC enantioseparation

Abstract

Chiral metal-organic frameworks (CMOFs) served as chiral stationary phases (CSPs) show great potential in enantioseparation field. However, their performance improvement are still hindered by the difficult column packed and high back pressure due to the irregular morphology and broad size scope of CMOF particles. Here, the size and morphology of achiral Co-MOF-74 were effectively adjusted by controlling the synthetic route, temperature, the ratio of reactants and the amount of 2-methylimidazole (2-MI) at first. As a result, the uniformly spherical crystals in size of about 5 μm with good dispersion were obtained. Subsequently, a simple, green post-synthetic modification strategy was proposed for the fabrication of l-tyrosine functionalized Co-MOF-74, namely Co-MOF-74-L-Tyr in H2O by incorporating l-tyrosine into the parent framework of Co-MOF-74 to construct chiral microenvironment. The homochiral Co-MOF-74-L-Tyr CSP gave superior enantioseparation performance for the eight chiral drugs and drug intermediates, such as nitrendipine, nimodipine, benzoin, 2,2′-furoin and bi-2-naphthol to the commercial columns under normal phase condition. The good repeatability and stability of this CSP was verified by the replicate enantioseparation for nimodipine and flavanone. Furthermore, the Co-MOF-74-L-Tyr packed column was successfully applied to detect the product N-1-(1-naphthyl)ethyltosylamide (HR-8) in the asymmetric reductive amination reaction. The size/morphology-controlled synthesis coupled with the green post-synthetic modification approach paves the way to fabricate target chiral MOFs with pre-designed functional groups, which is an effective complement for the preparation of CSPs in chiral chromatography.