Insights into the Mechanism of the Reaction between Tetrachloro‐p‐Benzoquinone and Hydrogen Peroxide and their Implications in the Catalytic Role of Water Molecules in Producing the Hydroxyl Radial

Abstract

Detailed mechanisms for the formation of hydroxyl or alkoxyl radicals in the reactions between tetrachloro-p-benzoquinone (TCBQ) and organic hydroperoxides are crucial for better understanding the potential carcinogenicity of polyhalogenated quinones. Herein, the mechanism of the reaction between TCBQ and H2O2 has been systematically investigated at the B3LYP/6-311++G** level of theory in the presence of different numbers of water molecules. We report that the whole reaction can easily take place with the assistance of explicit water molecules. Namely, an initial intermediate is formed first. After that, a nucleophilic attack of H2O2 onto TCBQ occurs, which results in the formation of a second intermediate that contains an OOH group. Subsequently, this second intermediate decomposes homolytically through cleavage of the O-O bond to produce a hydroxyl radical. Energy analyses suggest that the nucleophilic attack is the rate-determining step in the whole reaction. The participation of explicit water molecules promotes the reaction significantly, which can be used to explain the experimental phenomena. In addition, the effects of F, Br, and CH3 substituents on this reaction have also been studied.

Theoretical insights into the reaction mechanisms between 2,3,7,8-tetrachlorodibenzofuran and the methylidyne radical

“…Nowadays, the density functional theory (DFT) method has been widely applied in computational chemistry since its reliability and efficiency in predicting the geometries and properties has been veried by a lot of studies including the CH radical. [30][31][32][33][34][46][47][48][49][50][51][52][53][54][55][56][57] Therefore, all the species in the whole reactions have been fully optimized at the B3LYP/6-311++G** level of theory. Subsequently, vibrational frequency analysis has been performed at the same level of theory to identify the nature of the optimized structures.…”

Chloro-benzoquinones cause oxidative DNA damage through iron-mediated ROS production in Escherichia coli

“…Moreover, subsequent research displayed that HBQs produce 8-oxo-7,8-dihydro-2 0 -deoxyguanosine (8-oxodG), a DNA oxidative damage marker, more efficiently in double-stranded DNA (calf thymus DNA) than in dG under the participation of H 2 O 2 via not only a metal-independent but also an intercalation-enhanced oxidation mechanism (Yin et al, 2013). Finally, H 2 O 2 has been shown to attack the nucleophile of TCBQ and form an unstable TriCBQ-OOH intermediate that decomposes homolytically through the cleavage of the O-O bond to produce a hydroxyl radical with the assistance of water molecules (Zhu et al, 2007;Li et al, 2013). All these findings provide the possibility that the CBQ-induced DNA damage revealed in this study does not depend on iron, thus resulting in the partial maintenance of DNA when CBQ was added in the presence of iron chelators or ROS scavengers.…”

Theoretical Investigations on the Reactivity of Methylidyne Radical toward 2,3,7,8-Tetrachlorodibenzo-p-Dioxin: A DFT and Molecular Dynamics Study

“…Recently, the density functional theory (DFT) method has been widely applied in a variety of systems since it can provide many properties comparable in accuracy to experimental results and higher-level theories at a modest computational cost [ 36 , 37 , 38 , 39 , 40 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. In this study, considering the compromise between the computational cost and accuracy as well as to keep the consistency of the results for the optimization and molecular dynamics calculations using the same method, the B3LYP method [ 62 , 63 ] has been employed plus the 6-311++G** basis set, which has also been used to explore the reactivity of CH radical toward TCDF dioxin [ 51 ].…”