Abstract
Organophosphorus compounds (OP) are part of a group of compounds that may be hazardous to health. They are called neurotoxic agents because of their action on the nervous system, inhibiting the acetylcholinesterase (AChE) enzyme and resulting in a cholinergic crisis. Their high toxicity and rapid action lead to irreversible damage to the nervous system, drawing attention to developing new treatment methods. The diisopropyl fluorophosphatase (DFPase) enzyme has been considered as a potent biocatalyst for the hydrolysis of toxic OP and has potential for bioremediation of this kind of intoxication. In order to investigate the degradation process of the nerve agents Tabun, Cyclosarin and Soman through the wild-type DFPase, and taking into account their stereochemistry, theoretical studies were carried out. The intermolecular interaction energy and other parameters obtained from the molecular docking calculations were used to construct a data matrix, which were posteriorly treated by statistical analyzes of chemometrics, using the PCA (Principal Components Analysis) multivariate analysis. The analyzed parameters seem to be quite important for the reaction mechanisms simulation (QM/MM). Our findings showed that the wild-type DFPase enzyme is stereoselective in hydrolysis, showing promising results for the catalytic degradation of the neurotoxic agents under study, with the degradation mechanism performed through two proposed pathways.
Highlights
The use of chemical substances in wars was boosted in the 1930s with the discovery of the toxic properties of organophosphorus compounds (OP)
The most common way to graphically represent the results of the PCA decomposition is to plot, on a graph, the samples and weights of the principal components chosen, most often creating a two-dimensional graph that allows a clearer view of the arrangement of these samples and the contribution of the initial variables
It is important to keep in mind that the RP enantiomers of Cyclosarin and Tabun allowed a better interaction and stabilization in the active site, and this conformation led to the formation of hydrogen bonds with amino acid residues, unlike the SP enantiomer
Summary
The use of chemical substances in wars was boosted in the 1930s with the discovery of the toxic properties of organophosphorus compounds (OP). The members of this family, called nerve agents or neurotoxic agents, are the most lethal [5], due to their high toxicity Given these characteristics, they have potential for use warfare agents, beingagents, considered mass destruction weapons [2]. DFPase, there is yet no consensus in the literature describing the exact reaction pathway This feature indicates the need for a better understanding of the hydrolysis mechanisms and reactivity for the presented bioremediation process. There are certain resources available for treatment, there is not a universal antidote efficient against all existing OP agents In this context, considering that the bioremediation is an expanding field, and that the knowledge about the wild-type DFPase enzyme has brought significant contributions for the medicinal chemistry, more studies become necessary [10,14,15].
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