Detoxification of the Toxic Sulfur Mustard Simulant by a Supramolecular Antidote in Vitro and in Vivo
Detoxification of the Toxic Sulfur Mustard Simulant by a Supramolecular Antidote in Vitro and in Vivo
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超分子解毒剂对有毒硫芥模拟物的体外和体内解毒作用
DOI：
10.1021/acsami.1c15890
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发表时间：
2021
影响因子：
9.5
通讯作者：
Chen Shigui
中科院分区：
文献类型：
--
作者：
Zhou Siyuan;Li Wangzi;Zhao Qi;Dong Hongqiang;Wang Yueqi;Lu Feihong;Zhao Jiahao;Liu Shanshan;Chen Hong;Wang Lu;Liu Wei;Zhang Mingchang;Chen Shigui
虽然芥菜仍然存在巨大的潜在危害和威胁，但目前还没有针对芥菜中毒的专门药物或治疗方法。在此，我们已经证明了一种基于主-客相互作用的超分子方法，可以在体外和体内通过羧基聚束[5]芳烃钾盐（CP[5]AK1）有效地解毒芥菜模拟物cees(4)。采用1h NMR滴定法、密度泛函理论研究和独立梯度模型研究等方法研究了cees(4)与[5]- arene2矿柱空腔之间的C-H···π相互作用驱动了cees(4)被[5]- arene2矿柱空腔封装的机理。CEES(4)在水介质中迅速降解为反应性磺化盐，导致DNA和蛋白质的烷基化。CP[5] ak1能有效地包封磺胺盐，使磺胺盐的降解速度加快约14倍。细胞和动物实验表明，磺胺盐的生物活性被稳定的主客体复合物的形成所抑制，CP[5] ak1在处理前或处理后对cees引起的损伤都有良好的治疗作用(4)。阴离子柱[5]芳烃具有较低的细胞毒性和良好的治疗效果，有望作为芥子气（HD）的特异性解毒剂得到开发。
Although great potential hazards and threats still occur from sulfur mustard, there are no specific medicine or therapy for the intoxication of sulfur mustard. Herein, we have demonstrated a supramolecular approach for the detoxification of the sulfur mustard simulantCEES(4) in vitro and in vivo by carboxylatopillar[5]arene potassium salts (CP[5]AK1) efficiently based on host–guest interactions. The encapsulation ofCEES(4) by the cavity of the pillar[5]arene2is driven by C–H···π interactions betweenCEES(4) and the electron-rich cavity of pillar[5]arene2, which was investigated by1H NMR titration, density functional theory studies, and the independent gradient model studies.CEES(4) is degradated to the reactive sulfonium salts quickly in aqueous media, resulting in the alkylation of DNA and proteins. The sulfonium salts can be encapsulated by CP[5]AK1efficiently, which accelerates the degradation of the sulfonium salts about 14 times. The cell and animal experiments indicated that the bioactivities of the sulfonium salts are inhibited with the formation of stable host–guest complexes, and CP[5]AK1has a good therapeutic effect on the damages caused byCEES(4) at either pre- or post-treatments. Due to the low cytotoxicity and good therapeutic effect, the anionic pillar[5]arenes are expected to be developed as specific antidotes against sulfur mustard (HD).