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乙酰氧肟酸盐:对抗诺维乔克神经毒剂的温和、简便且有效的降解试剂。

Acetohydroxamic acid salts: mild, simple and effective degradation reagents to counter Novichok nerve agents.

作者信息

Smolkin Boris, Nahum Victoria, Bloch-Shilderman Eugenia, Nili Uri, Fridkin Gil, Ashkenazi Nissan

机构信息

Department of Organic Chemistry, IIBR-Israel Institute for Biological Research PO Box 19 7410001 Ness Ziona Israel

Department of Pharmacology, IIBR-Israel Institute for Biological Research PO Box 19 7410001 Ness Ziona Israel.

出版信息

RSC Adv. 2024 May 8;14(21):14904-14909. doi: 10.1039/d4ra02038c. eCollection 2024 May 2.

Abstract

Novichoks is the latest known class of organophosphorus nerve agents to be developed. These highly lethal persistent agents, which exert their toxicity mainly through dermal exposure, pose new major challenges in mitigating their effect, mainly in respect to decontamination and medical countermeasures. Herein we report on the effective degradation of Novichok agents (A-230, A-232 and A-234) by hydroxamic acid salts. This class of α-nucleophiles, with emphasis on the FDA approved drug acetohydroxamic acid, were found to promote rapid hydrolysis of these extremely toxic agents. Using P NMR the Novichoks degradation rates were determined to be in time scale of minutes with the following order of reactivity A-230>A-232>A-234. The degradation efficiency was found to be dependent on the nucleophiles, their counter-cations and the specific solvent mixture used. Hence, these scavengers can serve as efficient and mild decontaminants in various scenarios including surfaces, dermal decontamination (as an alternative to active lotions such as the RSDL® kit) and also as a medical countermeasure in the form of "catch-up therapy".

摘要

诺维乔克是已知最新研发的一类有机磷神经毒剂。这些高致死性的持久性毒剂主要通过皮肤接触发挥毒性作用,在减轻其影响方面带来了新的重大挑战,主要涉及去污和医学应对措施。在此,我们报告异羟肟酸盐对诺维乔克毒剂(A - 230、A - 232和A - 234)的有效降解作用。发现这类α - 亲核试剂,尤其是美国食品药品监督管理局批准的药物乙酰异羟肟酸,能促进这些剧毒毒剂的快速水解。利用磷核磁共振确定诺维乔克毒剂的降解速率在几分钟的时间尺度内,反应活性顺序为A - 230 > A - 232 > A - 234。发现降解效率取决于亲核试剂、它们的抗衡阳离子以及所使用的特定溶剂混合物。因此,这些清除剂可在包括表面去污、皮肤去污(作为如RSDL®试剂盒等活性洗剂的替代品)等各种场景中作为高效且温和的去污剂,还可作为“追赶疗法”形式的医学应对措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e83c/11077324/c205c7c90278/d4ra02038c-f1.jpg

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