Acyclic Cucurbit[n]uril as Supramolecular Antagonist for Rapidly Reversing the Neuromuscular Blockade of Succinylcholine through Host-Guest Complexation

doi:10.6023/cjoc202601042

Abstract

Seven new acyclic cucurbit[n]urils have been prepared. One of the compounds (ACB-p2) displays high water-solubility and high biocompatibility, with maximum tolerated dose reaching 1500 mg/kg for mice. The compound is revealed to have high binding affinity (K_a = 1.7 × 10⁵ M^-1) in water for succinylcholine (SCH), clinically used short-duration neuromuscular blocking agent. ¹H NMR and density functional theory calculation show that ACB-p2 binds to SCH mainly by encapsulating the choline segment of SCH in its hydrophobic cavity, which is stabilized by multiple intermolecular C-H۰۰۰O hydrogen bonds. The high binding affinity of ACB-p2 for SCH leads to rapid antagonism of the neuromuscular blockade of SCH. For rats, compound ACB-p2 of the 80 and 160 mg/kg doses is capable of shortening the recovery time for spontaneous respiration averagely from 195 seconds to 38 and 23 seconds, respectively, corresponding to therapeutic an index of 11.8 and 5.9.

Key words: host-guest chemistry, acyclic cucurbit[n]uril, succinylcholine, antidote, neuromuscular blockade, supramolecular antagonism, drug design

Cite this article

Dan-Wei Zhang, Rui Gao, Ke Feng, Shang-Bo Yu, Hui Wang, Wei Zhou, Zhan-Ting Li. Acyclic Cucurbit[n]uril as Supramolecular Antagonist for Rapidly Reversing the Neuromuscular Blockade of Succinylcholine through Host-Guest Complexation[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202601042.

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