Instantaneous Hydrolysis of Methyl Paraoxon Nerve Agent Simulant Is Catalyzed by Nontoxic Aminoguanidine Imines

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.