Abstract
Exposure to organophosphate-based nerve agents and pesticides poses health and security threats to civilians, soldiers, and first responders. Thus, there is a need to develop effective decontamination agents that are nonhazardous to human health. To address this, we demonstrate that instantaneous hydrolysis of methyl paraoxon (Me-POX), a nerve agent simulant, can be achieved in the presence of aminoguanidine imines at pH 10: ● the pyridine-4-aldehyde aminoguanidine-imine (1) and ● the 2,3-butanedione aminoguanidine-imine (2). The hydrolysis of Me-POX under these conditions is substantially faster than that of the state-of-the-art decontaminating agent, Dekon-139 (2,3-butanedione oxime, potassium salt). Furthermore, Dekon-139 shows adverse effects when applied on skin surfaces, making it of great interest to develop safer but effective decontaminating agents for neutralizing nerve agents and pesticides exposed to skin-surface areas. Our pharmaceutically relevant aminoguanidine derivatives serve as rather nontoxic and safe decontaminating agents for organophosphate-based nerve agents and pesticides. The hydrolytic degradation products of Me-POX by our aminoguanidine-based imines and Dekon-139 are pH dependent. At pH > 10, Me-POX is hydrolyzed to give dimethyl phosphate as the exclusive product, whereas at pH < 9, the major product of hydrolysis is methyl 4-nitrophenyl phosphate (M4NP). We applied Quantum Mechanics calculations to investigate the mechanism of this dramatically accelerated decontamination process. We predict that in the rate-determining transition state, both 1 and 2 stabilize the reaction center through hydrogen bonding. Compared to Dekon-139, the rate constants of the rate-determine steps (RDS) are predicted to be over 9,000 times larger for 1 and over 600 times larger for 2, explaining the improvement. Quantum Mechanics calculations rationalize the pH-dependent hydrolysis products of the Me-POX in the gas phase, and gauge-including atomic orbital (GIAO)-31P NMR chemical shift calculations confirm the experimental values.
Recommended Citation
E. K. Darkwah et al., "Instantaneous Hydrolysis of Methyl Paraoxon Nerve Agent Simulant is Catalyzed by Nontoxic Aminoguanidine Imines," ACS Omega, American Chemical Society, Jan 2025.
The definitive version is available at https://doi.org/10.1021/acsomega.4c09946
Department(s)
Chemistry
Publication Status
Open Access
International Standard Serial Number (ISSN)
2470-1343
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2025 American Chemical Society, All rights reserved.
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution 4.0 License.
Publication Date
01 Jan 2025
Comments
U.S. Department of Defense, Grant W911NF-21-2-0259