Acetohydroxamic acid salts: mild, simple and effective degradation reagents to counter Novichok nerve agents
Boris Smolkin1, Victoria Nahum1, Eugenia Bloch-Shilderman2
1Department of Organic Chemistry, IIBR-Israel Institute for Biological Research PO Box 19 7410001 Ness Ziona Israel boriss@iibr.gov.il victorian@iibr.gov.il nissan.ashkenazi@iibr.gov.il.
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 31P 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".
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