Miao Pandeng, Yan Yifan, Du Shuaijing, Du Yingxiang
Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing, 210009, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, PR China.
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095, USA.
Anal Chim Acta. 2024 Nov 22;1330:343303. doi: 10.1016/j.aca.2024.343303. Epub 2024 Oct 4.
Chirality is one of the most fundamental features of nature. In terms of biological activities, pharmacological effects, etc., enantiomers often show great differences among each other. Therefore, it is important to develop highly efficient enantioseparation and analysis methods. Capillary electrochromatography (CEC) is one of the most popular methods in the field of enantioseparation. In the chiral stationary phase of CEC, chiral molecularly imprinted polymers (CMIPs) and chiral metal-organic frameworks (CMOFs) have shown great potential of enantioseparation. However, the enantioseparation performance of CMOFs and CMIPs alone as chiral separation media is less satisfactory.
In this work, a novel nanomaterial synthesized by CMOFs and CMIPs was used as stationary phase in CEC synergistic enantioseparation system and the relevant reports have not been internationally found by authors. As a proof-of-concept demonstration, a coated capillary column was prepared by a one-step method using l-malic acid (template), [Cu(D-Cam)Dabco] (Cu-MOF) and dopamine (functional monomer/cross-linking agent), which greatly simplified the modification process of the capillary columns. Compared with Cu-MOF and CMIP alone, the CEC synergistic enantioseparation system based on Cu-MOF@MIP has significantly better enantioseparation performance of malic acid enantiomers (resolution: 1.03/0.58 → 4.22), and there is also a satisfactory performance in the quantitative analysis in real samples. Finally, through molecular docking and adsorption experiments, it was systematically proved that Cu-MOF@MIP had a significantly stronger binding ability for l-malic acid than d-malic acid.
Cu-MOF with chiral recognition ability have synergize with CMIPs to greatly improve the chiral selectivity of Cu-MOF@MIP, which is firstly used for the construction of the CEC chiral separation system. This pioneering synergistic chiral separation system creates a potential direction for efficient enantioseparation. Considering the diversity of CMOFs and CMIPs, the stationary phases hold great promise in chiral separation science.
手性是自然界最基本的特征之一。在生物活性、药理作用等方面，对映体之间往往表现出很大差异。因此，开发高效的对映体分离和分析方法具有重要意义。毛细管电色谱（CEC）是对映体分离领域最常用的方法之一。在CEC的手性固定相中，手性分子印迹聚合物（CMIPs）和手性金属有机框架（CMOFs）展现出了巨大的对映体分离潜力。然而，单独作为手性分离介质的CMOFs和CMIPs的对映体分离性能并不理想。
在本研究中，一种由CMOFs和CMIPs合成的新型纳米材料被用作CEC协同对映体分离系统的固定相，作者在国际上尚未发现相关报道。作为概念验证示范，采用一步法以L-苹果酸（模板）、[Cu(D-Cam)Dabco]（Cu-MOF）和多巴胺（功能单体/交联剂）制备了涂覆毛细管柱，大大简化了毛细管柱的改性过程。与单独的Cu-MOF和CMIP相比，基于Cu-MOF@MIP的CEC协同对映体分离系统对苹果酸对映体具有显著更好的对映体分离性能（分离度：1.03/0.58 → 4.22），并且在实际样品的定量分析中也有令人满意的表现。最后，通过分子对接和吸附实验，系统地证明了Cu-MOF@MIP对L-苹果酸的结合能力明显强于D-苹果酸。
具有手性识别能力的Cu-MOF与CMIPs协同作用，极大地提高了Cu-MOF@MIP的手性选择性，首次用于构建CEC手性分离系统。这种开创性的协同手性分离系统为高效对映体分离创造了一个潜在方向。考虑到CMOFs和CMIPs的多样性，该固定相在手性分离科学中具有广阔前景。
