A computational methodology for accurate predictions of rate constants in solution: Application to the assessment of primary antioxidant activity

Galano, Annia; Álvarez-Idaboy, J. Raúl

doi:10.1002/jcc.23409

Cited by 317 publications

(594 citation statements)

References 131 publications

(133 reference statements)

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“…It is rather difficult to calculate the exact value of the reaction rate, as multiple factors should be considered, and appropriate DFT level should be used [46]. However, the location of TS point calculated for 3HAA–Met-OO* and XAA OXO −Met-OO* by B3LYP (level II) is similar to that calculated by XYG3 (level V) (S4 Fig).…”

Section: Resultsmentioning

confidence: 84%

Antioxidant Properties of Kynurenines: Density Functional Theory Calculations

et al. 2016

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Kynurenines, the main products of tryptophan catabolism, possess both prooxidant and anioxidant effects. Having multiple neuroactive properties, kynurenines are implicated in the development of neurological and cognitive disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases. Autoxidation of 3-hydroxykynurenine (3HOK) and its derivatives, 3-hydroxyanthranilic acid (3HAA) and xanthommatin (XAN), leads to the hyperproduction of reactive oxygen species (ROS) which damage cell structures. At the same time, 3HOK and 3HAA have been shown to be powerful ROS scavengers. Their ability to quench free radicals is believed to result from the presence of the aromatic hydroxyl group which is able to easily abstract an electron and H-atom. In this study, the redox properties for kynurenines and several natural and synthetic antioxidants have been calculated at different levels of density functional theory in the gas phase and water solution. Hydroxyl bond dissociation enthalpy (BDE) and ionization potential (IP) for 3HOK and 3HAA appear to be lower than for xanthurenic acid (XAA), several phenolic antioxidants, and ascorbic acid. BDE and IP for the compounds with aromatic hydroxyl group are lower than for their precursors without hydroxyl group. The reaction rate for H donation to *O-atom of phenoxyl radical (Ph-O*) and methyl peroxy radical (Met-OO*) decreases in the following rankings: 3HOK ~ 3HAA > XAAOXO > XAAENOL. The enthalpy absolute value for Met-OO* addition to the aromatic ring of the antioxidant radical increases in the following rankings: 3HAA* < 3HOK* < XAAOXO* < XAAENOL*. Thus, the high free radical scavenging activity of 3HAA and 3HOK can be explained by the easiness of H-atom abstraction and transfer to O-atom of the free radical, rather than by Met-OO* addition to the kynurenine radical.

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Section: Resultsmentioning

confidence: 84%

Antioxidant Properties of Kynurenines: Density Functional Theory Calculations

et al. 2016

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“…49 These computational details are in line with the quantum mechanics based test for overall free radical scavenging activity (QM-ORSA), 50 which has been validated by comparison with experimental results; its uncertainties have been proven to be no larger than those arising from experiments. 50 ■ RESULTS AND DISCUSION Free radical scavenging activity. The structures of NAS and 6OHM, as well as their site numbering are shown in Scheme 2.…”

Section: ■ Computational Detailsmentioning

confidence: 99%

N-Acetylserotonin and 6-Hydroxymelatonin against Oxidative Stress: Implications for the Overall Protection Exerted by Melatonin

et al. 2015

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The protection exerted by N-acetylserotonin (NAS) and 6-hydroxymelatonin (6OHM) against oxidative stress was investigated using the density functional theory. It was found that these compounds are better peroxyl radical scavengers than melatonin itself, Trolox, caffeine, or genistein both in lipid and aqueous solutions. The related kinetic data is provided for the first time. The solvent polarity influences not only the absolute reactivity of NAS and 6OHM toward peroxyl radicals, but also their relative scavenging activity. In addition, they both fully inhibit the oxidative effects of copper-ascorbate mixtures, and (•)OH production via the Haber-Weiss reaction, albeit the effects on the later are only partial. On the basis of comparisons with other melatonin-related compounds, it is proposed that the role of NAS and 6OHM on the overall protection exerted by melatonin against oxidative stress is mainly related to their free radical scavenging activities. Moreover, they increase such protection. The role of the phenol moiety on such activity is demonstrated.

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“…The kinetic data were estimated via the quantum mechanics-based test for overall free-radical scavenging activity (QM-ORSA) protocol [45]. This has been validated by comparison with experimental results, and the uncertainty associated with the results of this protocol have been proven to be no larger than those arising from experimental investigations.…”

Section: Computational Detailsmentioning

confidence: 99%

Free-radical scavenging by tryptophan and its metabolites through electron transfer based processes

2015

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Free-radical scavenging by tryptophan and eight of its metabolites through electron transfer was investigated in aqueous solution at physiological pH, using density functional theory and the Marcus theory. A test set of 30 free radicals was employed. Thermochemical and kinetic data on the corresponding reactions are provided here for the first time. Two different pathways were found to be the most important: sequential proton loss electron transfer (SPLET) and sequential double proton loss electron transfer (SdPLET). Based on kinetic analyses, it is predicted that the tryptophan metabolites kynurenic acid and xanthurenic acid are the best free-radical scavengers among the tested compounds; they were estimated to be at least 24 and 12 times more efficient than Trolox for scavenging (•)OOH. These findings are in line with previous reports suggesting that the antioxidant activity that has been attributed to tryptophan is actually due to its metabolites, and they demonstrate the particular importance of phenolic metabolites to such activity. Graphical Abstract Kynurenic acid (KNA) and xanthurenic acid (XNA) are the major contributors to the free-radical scavenging activity of tryptophan.

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A computational methodology for accurate predictions of rate constants in solution: Application to the assessment of primary antioxidant activity

Cited by 317 publications

References 131 publications

Antioxidant Properties of Kynurenines: Density Functional Theory Calculations

Antioxidant Properties of Kynurenines: Density Functional Theory Calculations

N-Acetylserotonin and 6-Hydroxymelatonin against Oxidative Stress: Implications for the Overall Protection Exerted by Melatonin

Free-radical scavenging by tryptophan and its metabolites through electron transfer based processes

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