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Two-step reaction mechanism reveals new antioxidant capability of cysteine disulfides against hydroxyl radical attack.

ABSTRACT: Cysteine disulfides, which constitute an important component in biological redox buffer systems, are highly reactive toward the hydroxyl radical (^•OH). The mechanistic details of this reaction, however, remain unclear, largely due to the difficulty in characterizing unstable reaction products. Herein, we have developed a combined approach involving mass spectrometry (MS) and theoretical calculations to investigate reactions of ^•OH with cysteine disulfides (Cys-S-S-R) in the gas phase. Four types of first-generation products were identified: protonated ions of the cysteine thiyl radical (⁺Cys-S^•), cysteine (⁺Cys-SH), cysteine sulfinyl radical (⁺Cys-SO^•), and cysteine sulfenic acid (⁺Cys-SOH). The relative reaction rates and product branching ratios responded sensitively to the electronic property of the R group, providing key evidence to deriving a two-step reaction mechanism. The first step involved ^•OH conducting a back-side attack on one of the sulfur atoms, forming sulfenic acid (-SOH) and thiyl radical (-S^•) product pairs. A subsequent H transfer step within the product complex was favored for protonated systems, generating sulfinyl radical (-SO^•) and thiol (-SH) products. Because sulfenic acid is a potent scavenger of peroxyl radicals, our results implied that cysteine disulfide can form two lines of defense against reactive oxygen species, one using the cysteine disulfide itself and the other using the sulfenic acid product of the conversion of cysteine disulfide. This aspect suggested that, in a nonpolar environment, cysteine disulfides might play a more active role in the antioxidant network than previously appreciated.

SUBMITTER: Adhikari S

PROVIDER: S-EPMC7414153 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Two-step reaction mechanism reveals new antioxidant capability of cysteine disulfides against hydroxyl radical attack.

Adhikari Sarju S Crehuet Ramon R Anglada Josep M JM Francisco Joseph S JS Xia Yu Y

Proceedings of the National Academy of Sciences of the United States of America 20200717 31

Cysteine disulfides, which constitute an important component in biological redox buffer systems, are highly reactive toward the hydroxyl radical (<sup>•</sup>OH). The mechanistic details of this reaction, however, remain unclear, largely due to the difficulty in characterizing unstable reaction products. Herein, we have developed a combined approach involving mass spectrometry (MS) and theoretical calculations to investigate reactions of <sup>•</sup>OH with cysteine disulfides (Cys-S-S-R) in the ...[more]

PMID: 32680962

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Project description:Understanding the mechanism of hydrazine oxidation reaction by OH radical along with the rate constants of all possible pathways leads to explain the fate of hydrazine in the atmosphere. In this article, the comprehensive mechanisms and kinetics of the hydrazine plus hydroxyl radical reaction have been investigated theoretically at different temperatures and pressures. To achieve the main goals, a series of high levels of quantum chemical calculations have been widely implemented in reliable channels of the H-abstraction, SN2, and addition/elimination reactions. The energy profile of all pathways accompanied by the molecular properties of the involved stationary points has been characterized at the MP2, M06-2X, and CCSD(T)/CBS levels. To estimate accurate barrier energies of the H-abstraction channels, large numbers of the CCSD (T) calculations in conjunction with various augmented basis sets have been implemented. The direct dynamic calculations have been carried out using the validated M06-2X/maug-cc-pVTZ level, and also by the CCSD(T) (energies) + MP2 (partition functions) level. The pressure-dependent rate constants of the barrierless pathways have been investigated by the strong collision approach. Therefore, the main behaviors of the N2H4 + OH reaction have been explored according to the influences of temperature and pressure on the computed rate coefficients within the well-behaved theoretical frameworks of the TST, VTST, and RRKM theories. It has been found that the H-abstraction mechanism (to form N2H3) is dominant relative to the SN2 reaction and OH-addition to the N center of N2H4 moiety (to form H2NOH + NH2). The computed high pressure limit rate constant of the main reaction pathway, k(298.15) = 7.31 × 10-11 cm3 molecule-1 s-1, has an excellent agreement with the experimental value (k (298.15) = (6.50 ± 1.3) × 10-11 cm3 molecule-1 s-1) recommended by Vaghjiani. Also, the atmospheric lifetime of hydrazine degradation by OH radicals has been demonstrated to be 32.80 to 1161.11 h at the altitudes of 0-50 km. Finally, the disagreement in the calculated rate constants between the previous theoretical study and experimental results has been rectified.

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Two-step reaction mechanism reveals new antioxidant capability of cysteine disulfides against hydroxyl radical attack.

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Two-step reaction mechanism reveals new antioxidant capability of cysteine disulfides against hydroxyl radical attack.

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