Gao Xiaoyue, Ben Teng
Department of Chemistry, Jilin University, Changchun, PR China.
Zhejiang Engineering Laboratory for Green Syntheses and Applications of Fluorine-Containing Specialty Chemicals, Institute of Advanced Fluorine-Containing Materials, Zhejiang Normal University, Jinhua, PR China.
Nat Commun. 2025 Jun 5;16(1):5210. doi: 10.1038/s41467-025-60572-0.
Chiral drugs are essential in modern medicine, but separating their enantiomers is challenging due to their similar physicochemical properties. However, traditional methods are often costly and inefficient. Here we show that chiral covalent organic framework (CCOF-300) membranes, induced by chiral dopants (L-( + )-/D-(-)-tartaric acid), can achieve high enantioselectivity in separating chiral drugs. Specifically, CCOF-300 membrane achieved 100% enantiomeric excess in separating racemic N-Fmoc-N'-[1-(4,4-Dimethyl-2,6-dioxocyclohexylidene)ethyl]-lysine (Fmoc-Lys(Dde)-OH). We found that size matching and differences in diffusion rates between enantiomers are key factors in chiral separation. Additionally, there were no significant differences in the binding energy between ibuprofen (IBU), Fmoc-Lys(Dde)-OH, and CCOF-300, indicating that binding energy is not the dominant factor in chiral separation. This study proposes a cost-effective and scalable method for chiral drug separation, highlighting the potential of chiral induction strategy in improving chiral separation technology in the pharmaceutical industry.
手性药物在现代医学中至关重要，但由于其对映体具有相似的物理化学性质，分离它们具有挑战性。然而，传统方法往往成本高昂且效率低下。在此我们表明，由手性掺杂剂（L-(+)-/D-(-)-酒石酸）诱导的手性共价有机框架（CCOF-300）膜在分离手性药物时可实现高对映选择性。具体而言，CCOF-300膜在分离外消旋N-芴甲氧羰基-N'-[1-(4,4-二甲基-2,6-二氧代环己亚基)乙基]-赖氨酸（Fmoc-Lys(Dde)-OH）时实现了100%的对映体过量。我们发现尺寸匹配以及对映体之间扩散速率的差异是手性分离的关键因素。此外，布洛芬（IBU）、Fmoc-Lys(Dde)-OH与CCOF-300之间的结合能没有显著差异，这表明结合能不是手性分离的主导因素。本研究提出了一种经济高效且可扩展的手性药物分离方法，突出了手性诱导策略在改进制药行业手性分离技术方面的潜力。
