Scholarlink

<p>Host-guest binding has been used to develop a universal antagonistic agent for clinically used neuromuscular blocking agents (NMBAs) by preparing ten deuterated acyclic cucurbit[<i>n</i>]urils (ACBs). Train-of-four test with rats reveals that, compared with the nondeuterated counterpart, tetradeuterated compound <b>dACB-4</b> displays improved activity for reversing the blockade of all clinically used NMBAs, particularly cisatracurium with 43% improvement. Binding constant measurement supports that deuteration provides <b>dACB-4</b> with increased binding affinity for all NMBAs. The dynamic light scattering experiment shows that, different from the nondeuterated counterpart, which undergoes strong self-aggregation, <b>dACB-4</b> does not aggregate even at the high concentration of 60 mM. Density functional theory calculation illustrates that deuteration causes the acidity of the CH units to reduce by 1 p<i>K</i><sub>a</sub> unit. Thus, the activity improvement of <b>dACB-4</b> has been tentatively attributed to the contribution of deuteration to weaken intermolecular hydrogen bonds and thus its self-aggregation. <i>In vitro</i> and <i>in vivo</i> studies further confirm that <b>dACB-4</b> also has improved biocompatibility, with general performance surpassing that of all reported ACBs.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Deuteration for enhancing the antagonistic activity of an acyclic cucurbit[n]uril for neuromuscular blocking agents through host-guest complexation

  • 期刊论文

  • 发表日期：

    2026年2月3日

查看全文
  • Ke Feng,
  • Yue-Yang Liu,
  • Cui Yu,
  • Haofeng Zhu,
  • Yang Zong,
  • Zhuo Lei,
  • Sheng-Yi Zhuang,
  • Yan Wu,
  • Shang-Bo Yu,
  • Qiao-Yan Qi,
  • Jia Tian,
  • Wei Zhou,
  • Da Ma,
  • Gang Zhao,
  • Xiao-Song Xue,
  • Dan-Wei Zhang,
  • Zhan-Ting Li

摘要

Host-guest binding has been used to develop a universal antagonistic agent for clinically used neuromuscular blocking agents (NMBAs) by preparing ten deuterated acyclic cucurbit[n]urils (ACBs). Train-of-four test with rats reveals that, compared with the nondeuterated counterpart, tetradeuterated compound dACB-4 displays improved activity for reversing the blockade of all clinically used NMBAs, particularly cisatracurium with 43% improvement. Binding constant measurement supports that deuteration provides dACB-4 with increased binding affinity for all NMBAs. The dynamic light scattering experiment shows that, different from the nondeuterated counterpart, which undergoes strong self-aggregation, dACB-4 does not aggregate even at the high concentration of 60 mM. Density functional theory calculation illustrates that deuteration causes the acidity of the CH units to reduce by 1 pKa unit. Thus, the activity improvement of dACB-4 has been tentatively attributed to the contribution of deuteration to weaken intermolecular hydrogen bonds and thus its self-aggregation. In vitro and in vivo studies further confirm that dACB-4 also has improved biocompatibility, with general performance surpassing that of all reported ACBs.