Nerve Agents: A Comprehensive Review

Abstract

Nerve agents are perhaps the most feared of potential agents of chemical attack. The authors review the history, physical characteristics, pharmacology, clinical effects, and treatment of these agents.

Spectroscopic and mechanistic studies of dinuclear metallohydrolases and their biomimetic complexes

“…The question is how to eliminate the residues of these compounds from the environment to avoid hazards for aquatic organisms and human health? [52][53][54][55] As well as use as pesticides, OPs have also been used as nerve agents, for example, sarin or VX. 54 It is proposed that the mode of action of these compounds involves the organophosphate molecule undergoing nucleophilic attack by a serine-OH moiety in the active site of the enzyme acetylcholine esterase (AChE), subsequently blocking the site for the neurotransmitter acetylcholine.…”

“…54 It is proposed that the mode of action of these compounds involves the organophosphate molecule undergoing nucleophilic attack by a serine-OH moiety in the active site of the enzyme acetylcholine esterase (AChE), subsequently blocking the site for the neurotransmitter acetylcholine. 54,55 With the enzyme inhibited, acetylcholine builds up in the synapses and nerve impulses are continually transmitted. The resulting dysfunction of the parasympathetic nervous system may lead to the death of the organism.…”

“…Thiophosphates are less potent AChE inhibitors than the corresponding oxophosphates. 54,55 This is due to the former being more stable and thus less likely to react with AChE. However, desulfurization in vivo leads to a high acute toxicity of the thiophosphate pesticides.…”

Immobilization of the enzyme GpdQ on magnetite nanoparticles for organophosphate pesticide bioremediation

“…The use of pesticides has distinct benefits but there are risks to people and the environment, especially in developing countries. How to eliminate these compounds from the environment to avoid contamination of waterways and deleterious effects on human health has been raised [1][2][3][4]. As well as pesticides, OPs have also been used as nerve agents, for example sarin and VX (Chart 1) [3].…”

“…Furthermore, recent directed evolution experiments have indicated that the catalytic activity of GpdQ can be significantly enhanced by the introduction of a small number of mutations [13]. 4 The most recent crystal structure of GpdQ at high resolution (1.9 Å) illustrates an extensive hydrogen bonding network in the active site, the latter composed of two distinct metal binding sites (labelled as the α and β-sites, Chart 1) [14]. The α-site features four amino acid side chains, two aspartates (Asp50, Asp8) and two histidines (His10, His197), whereas the metal in the β-site is coordinated by two histidines (His156, His195), one aspartate (Asp50) and one asparagine (Asn80).…”