Detoxification of the Toxic Sulfur Mustard Simulant by a Supramolecular Antidote in Vitro and in Vivo
| Autor: | Wangzi Li, Qi Zhao, Shanshan Liu, Jiahao Zhao, Hong Chen, Mingchang Zhang, Shigui Chen, Feihong Lu, Wei Liu, Yueqi Wang, Hongqiang Dong, Lu Wang, Siyuan Zhou |
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| Rok vydání: | 2021 |
| Předmět: |
Materials science
Eye Diseases Cell Survival Macromolecular Substances Sulfonium Potassium Antidotes Respiratory Tract Diseases Supramolecular chemistry chemistry.chemical_element Alkylation Medicinal chemistry chemistry.chemical_compound In vivo Materials Testing Mustard Gas Animals Humans General Materials Science Cytotoxicity Density Functional Theory Molecular Structure Sulfur mustard Rats HEK293 Cells chemistry Salts Titration |
| Zdroj: | ACS Applied Materials & Interfaces. 13:58291-58300 |
| ISSN: | 1944-8252 1944-8244 |
| DOI: | 10.1021/acsami.1c15890 |
| Popis: | 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 simulant CEES (4) in vitro and in vivo by carboxylatopillar[5]arene potassium salts (CP[5]AK 1) efficiently based on host-guest interactions. The encapsulation of CEES (4) by the cavity of the pillar[5]arene 2 is driven by C-H···π interactions between CEES (4) and the electron-rich cavity of pillar[5]arene 2, which was investigated by 1H 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]AK 1 efficiently, 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]AK 1 has a good therapeutic effect on the damages caused by CEES (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). |
| Databáze: | OpenAIRE |
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