Density Functional Theory (DFT) Study of Edaravone Derivatives as Antioxidants

Borges, Rosivaldo S.; Queiroz, Auriekson N.; Mendes, Anna P. S.; Araújo, Sanderson Corrêa; França, Luiz C. S.; Franco, Edna Cristina Santos; Leal, Walter S.; Silva, Albérico Borges Ferreira da

doi:10.3390/ijms13067594

Cited by 26 publications

(20 citation statements)

References 22 publications

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“…Aromatic OH group diminishes IP values for 3HOK, 3HAA, and XAA relative to KYN, AA, and KYNA. Our results confirm the correlation between BDE and IP also shown by Borges [56]. Negatively charged carboxylic group significantly diminishes BDE and IP values, while positively charged amino group enhances them.…”

Section: Discussionsupporting

confidence: 92%

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: Discussionsupporting

confidence: 92%

Antioxidant Properties of Kynurenines: Density Functional Theory Calculations

et al. 2016

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“…The antioxidant capacity of phenolic compounds and all compounds in general is also attributed to their ability to chelate metal ions involved in the production of free radicals . Based on the optimized structure of the title compound, the PABOON analysis (Table ) was carried out to examine the relationship between the electrochemical properties and molecular structures of potential antioxidants . A high electron density is located at the carbonyl oxygen O 21 and the oxygen atom of the phenolic group O 27 .…”

Section: Resultsmentioning

confidence: 99%

4‐Hydroxy‐benzoic acid (4‐diethylamino‐2‐hydroxy‐benzylidene)hydrazide: DFT, antioxidant, spectroscopic and molecular docking studies with BSA

2015

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The Schiff base 4-hydroxy-benzoic acid (4-diethylamino-2-hydroxy-benzylidene) hydrazide (SL) was synthesized and characterized. Its antioxidant activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging action. Being a potent antioxidant its binding ability to the transport protein bovine serum albumin (BSA) was studied using fluorescence quenching and circular dichroism (CD) studies. The binding distance has been calculated by fluorescence resonance energy transfer (FRET) to be 1.85 Å and the Stern-Volmer quenching constant has been calculated to be (3.23 ± 0.45) × 10(5) M(-1). Quantum chemical analysis was carried out for the Schiff base using DFT with B3LYP and 6-311G** and related to the experimentally obtained results. For a deeper understanding of the mechanism of the interaction, the experimental data were complemented by protein-Schiff base docking calculations using Argus Lab.

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“…It is to be noted that the dimmer [DMDHFE] 2 is formed (similar to the reaction (5) 2 is not the end product of the reaction between DPPH* and DMDHFE. The optimized structure of the dimmer [DMDHFE] 2 is shown in Figure 4.…”

Section: In Their Turn the New Ions [Ah]mentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

“…As far as we know, there are none quantum-chemical studies clarifying the mechanisms of the reactions of DHFA and its derivatives with DPPH*. Only a number of quantum chemical calculations were mainly devoted to determination of the structure-antioxidant activity relationships for various free radical scavengers [5,6].In this context the aim of the present work is twofold: to reveal (using DFT calculations) the preferred mechanism of reaction between DHFA and DPPH*; to explain the decrease in the antioxidant activity by passing from DHFA to one of its derivatives, namely, to its dimethyldihydroxyfumarate ether -DMDHFE. …”

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confidence: 99%

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Antioxidant Properties of Dihydroxyfumaric Acid and Its Dimethyl Ether: a Comparative DFT Study of Their Reactions with the Stable Radical DPPH*

Gorbachev¹,

Gorinchoy²,

Arsene³

2015

ChemJMold

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Abstract. The preferred mechanism of the reaction of dihydroxyfumaric acid and its dimethyl ether with the free stable radical 1,1-diphenyl-2-picrylhydrazyl (DPPH*) was revealed by means of Density Functional Theory (DFT) calculations. The proposed mechanism has an ionic character and includes the formation of charge-transfer complexes as the main stage. It is also shown that the lower antioxidant activity of dimethyl ether of dihydroxyfumaric acid is caused by both its lower acidity (as compared with its precursor acid) and formation of more stable intermediates during its reaction with DPPH*. Our results allow one to rationalize the available experimental data.Keywords: antioxidant activity, DPPH*, dihydroxyfumaric acid, dimethyl ether of dihydroxyfumaric acid, DFT calculations. IntroductionMany organic compounds with enol or phenol groups are effective antioxidants which transform various free radicals into their diamagnetic derivatives [1]. Usually their relative antioxidant activity is evaluated by the reaction rate with the free stable radical -DPPH* (1,1-diphenyl-2-picrylhydrazyl) in the methanol-water medium. It was shown [2] that DPPH* reacts with compounds containing active hydrogen atoms (phenols, mineral and organic acids, etc.) forming 1,1-diphenyl-2-picrylhydrazine. According to [2], DPPH* solutions immediately change their color by adding of diluted aqueous mineral acids therein, in methanol or ethanol (whose acidity is lower) they demonstrate change of the color within several days, while solutions of DPPH* in liquid media without active hydrogen atoms (for instance, in benzene, chloroform, acetone, etc.) remain unchanged within a period of 50 days. Thus, the higher acidity of liquid media leads to the faster decomposition of DPPH*.In its turn, the rate of the reaction of DPPH* with some phenols depends on the stability of the free radicals formed from the above phenol diamagnetic molecules when their hydrogen atoms migrate to DPPH* ones. So, for example, isoeugenol reacts very quickly (immediately) with DPPH*, while the reaction between DPPH* and eugenol (whose double bond is not conjugated with its benzene cycle) requires several hours (see [1]). It has been also shown [1] that the compounds containing enol groups (ascorbic acid and isoascorbic one) possess the maximum antioxidant activity, i. e. they are the best scavengers of the free radical DPPH*.The other effective antioxidant compounds containing in their structures enol groups are the dihydroxyfumaric acid -DHFA and its derivatives (for instance, its dialkylethers). In the work [3] it was shown by means of the method of stopped-fl ow that in the methanol-water medium the reaction between DHFA and DPPH* includes two stages. During the fi rst stage which requires only 7-10 s at T = 293.15K one half of DPPH* reacts with DHFA. The second reaction step is slower and requires around 1-2 hours [3]. Basing on these facts, some theoretical suppositions were done [3] in order to describe the reaction mechanism between DPPH* and DHFA. So, it was a...

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Density Functional Theory (DFT) Study of Edaravone Derivatives as Antioxidants

Cited by 26 publications

References 22 publications

Antioxidant Properties of Kynurenines: Density Functional Theory Calculations

Antioxidant Properties of Kynurenines: Density Functional Theory Calculations

4‐Hydroxy‐benzoic acid (4‐diethylamino‐2‐hydroxy‐benzylidene)hydrazide: DFT, antioxidant, spectroscopic and molecular docking studies with BSA

Antioxidant Properties of Dihydroxyfumaric Acid and Its Dimethyl Ether: a Comparative DFT Study of Their Reactions with the Stable Radical DPPH*

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