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Hydrolysis of nerve agents by model nucleophiles: a computational study
Jeremy M Beck1, Christopher M Hadad
1Department of Chemistry, The Ohio State University, 100 W. 18th Avenue, Columbus, OH 43210, USA.
Chemico-Biological Interactions
|June 10, 2008
Summary
Density functional theory reveals nerve agent reactions with nucleophiles. Charged nucleophiles like ethoxide show exothermic reactions, while neutral nucleophiles exhibit endothermic reactions, with solvation significantly impacting charged species.
Area of Science:
- Computational Chemistry
- Toxicology
- Biochemistry
Background:
- Nerve agents pose significant threats, necessitating research into their mechanisms of action.
- Understanding the chemical reactions of nerve agents with biological nucleophiles is crucial for developing effective countermeasures.
Purpose of the Study:
- To investigate the reaction pathways and thermochemistry of nerve agents with model nucleophiles using computational methods.
- To compare the reactivity of charged versus neutral nucleophiles (ethoxide, ethanethiolate, ethaneselenolate) with nerve agents.
- To assess the influence of solvation on these reactions.
Main Methods:
- Density Functional Theory (DFT) calculations were performed.
- The B3LYP/6-311++G(2d,p) level of theory was utilized.
- A polarizable continuum model (PCM) simulated solvation effects, specifically in chloroform.
Main Results:
- Reactions between ethoxide (EtO-) and nerve agents were predicted to be exothermic.
- Reactions with ethanethiolate (EtS-) and ethaneselenolate (EtSe-) were significantly more endothermic than with ethoxide.
- Neutral nucleophiles (EtXH) exhibited more endothermic reactions compared to their charged counterparts.
- Solvation modeling showed a substantial exothermic shift for charged nucleophile reactions, but a minimal shift for neutral nucleophiles.
Conclusions:
- The nucleophilicity of EtX- decreases in the order O > S > Se, impacting reaction energetics.
- Charged nucleophiles are more reactive towards nerve agents than neutral ones.
- Solvation plays a critical role in the reaction thermochemistry, particularly for charged nucleophiles, influencing their efficacy in mitigating nerve agent toxicity.
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