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Issue 2, 2019
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A theoretical insight into the reaction mechanisms of a 2,4,6-trinitrotoluene nitroso metabolite with thiols for toxic effects

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Abstract

2,4,6-Trinitrotoluene (TNT) is a class C carcinogen as rated by the Environmental Protection Agency. One of the toxicity mechanisms of TNT is the covalent binding of its metabolites to critical proteins. However, knowledge about their molecular reaction mechanisms is scarce. Herein, we have provided density functional theory (DFT) simulation evidences for the reaction mechanisms of the nitroso metabolite of TNT with the sulfhydryl group of model thiols for the first time. The results show that the solvent-mediated proton-transfer mechanism plays a significant role in the entire process. For the formation of semimercaptal, the mechanism is slightly different from the previous one where the thiolate anion attacks the nitroso group. The rearrangement of semimercaptal needs to be triggered by an acid or hydrated ion (H3O+), which is consistent with the previous assumption. The other pathway, the conversion of semimercaptal to hydroxylamine, has to overcome a higher barrier, although it does not need the participation of an acid or a hydrated ion. In addition, the details on transition states, intermediates and free energy surfaces for three reactions are given, which make up for the lack of experimental knowledge. These conclusions can help to deeply understand the toxic effects of TNT and other nitroaromatic explosives.

Graphical abstract: A theoretical insight into the reaction mechanisms of a 2,4,6-trinitrotoluene nitroso metabolite with thiols for toxic effects

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Publication details

The article was received on 05 Dec 2018, accepted on 31 Jan 2019 and first published on 01 Feb 2019


Article type: Paper
DOI: 10.1039/C8TX00326B
Citation: Toxicol. Res., 2019,8, 270-276

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    A theoretical insight into the reaction mechanisms of a 2,4,6-trinitrotoluene nitroso metabolite with thiols for toxic effects

    Y. Zhou, X. Liu, W. Jiang, Y. Shu and G. Xu, Toxicol. Res., 2019, 8, 270
    DOI: 10.1039/C8TX00326B

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