柔性有机框架可隔离神经肌肉阻滞剂并逆转神经肌肉阻滞。
Flexible organic frameworks sequester neuromuscular blocking agents and reverse neuromuscular block .
作者信息
Wu Yan, Liu Yue-Yang, Liu Hong-Kun, Yu Shang-Bo, Lin Furong, Zhou Wei, Wang Hui, Zhang Dan-Wei, Li Zhan-Ting, Ma Da
机构信息
Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University Shanghai 200438 China
Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules, Shanghai Institute of Organic Chemistry (SIOC), Chinese Academy of Sciences 345 Lingling Lu Shanghai 200032 China.
出版信息
Chem Sci. 2022 Jul 20;13(32):9243-9248. doi: 10.1039/d2sc02456j. eCollection 2022 Aug 17.
Supramolecular sequestration and reversal of neuromuscular block (NMB) have great clinical applications. Water-soluble flexible organic frameworks (FOFs) cross-linked by disulfide bonds are designed and prepared. Different linker lengths are introduced to FOFs to give them varied pore sizes. FOFs are anionic nanoscale polymers and capable of encapsulating cationic neuromuscular blocking agents (NMBAs), including rocuronium (Roc), vecuronium (Vec), pancuronium (Panc) and cisatracurium (Cis). A host-guest study confirms that FOFs bind NMBAs in water. The multivalency interaction between FOFs and NMBAs is able to sequester NMBAs, and prevent them from escaping. These FOFs are non-toxic and biocompatible. Animal studies show that FOFs are effective for the reversal of NMB induced by Roc, Vec and Cis, which shorten the time to a train-of-four ratio of 0.9 by 2.6, 3.8 and 5.7-fold compared to a placebo, respectively.
超分子螯合与神经肌肉阻滞（NMB）的逆转具有重大临床应用价值。设计并制备了通过二硫键交联的水溶性柔性有机框架（FOF）。向FOF中引入不同长度的连接体以赋予其不同的孔径。FOF是阴离子纳米级聚合物，能够包封阳离子神经肌肉阻滞剂（NMBA），包括罗库溴铵（Roc）、维库溴铵（Vec）、泮库溴铵（Panc）和顺式阿曲库铵（Cis）。一项主客体研究证实FOF在水中能与NMBA结合。FOF与NMBA之间的多价相互作用能够螯合NMBA，并防止其逸出。这些FOF无毒且具有生物相容性。动物研究表明，FOF对Roc、Vec和Cis诱导的NMB逆转有效，与安慰剂相比，分别将四个成串刺激比值达到0.9的时间缩短了2.6倍、3.8倍和5.7倍。
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