title: Density functional theory (DFT) study of edaravone derivatives as antioxidants.
abstract: Quantum chemical calculations at the B3LYP/6-31G* level of theory were employed for the structure-activity relationship and prediction of the antioxidant activity of edaravone and structurally related derivatives using energy (E), ionization potential (IP), bond dissociation energy (BDE), and stabilization energies (ΔE(iso)). Spin density calculations were also performed for the proposed antioxidant activity mechanism. The electron abstraction is related to electron-donating groups (EDG) at position 3, decreasing the IP when compared to substitution at position 4. The hydrogen abstraction is related to electron-withdrawing groups (EDG) at position 4, decreasing the BDE(CH) when compared to other substitutions, resulting in a better antioxidant activity. The unpaired electron formed by the hydrogen abstraction from the C-H group of the pyrazole ring is localized at 2, 4, and 6 positions. The highest scavenging activity prediction is related to the lowest contribution at the carbon atom. The likely mechanism is related to hydrogen transfer. It was found that antioxidant activity depends on the presence of EDG at the C(2) and C(4) positions and there is a correlation between IP and BDE. Our results identified three different classes of new derivatives more potent than edaravone.
authors: Amazon Nucleus of Studies and Selection of Biomolecules, Institute of Health Sciences, Federal University of Pará, 66075-110, Belém, PA, Brasil.|Postgraduate Program in Neuroscience and Cell Biology, Institute of Biological Sciences, Federal University of Pará, 66075-110, Belém, PA, Brasil.|Institute of Chemistry of São Carlos, University of São Paulo, CP 780, 13560-970, São Carlos, SP, Brasil.
authors: Rosivaldo S
authors: RS
authors: Borges
authors: Amazon Nucleus of Studies and Selection of Biomolecules, Institute of Health Sciences, Federal University of Pará, 66075-110, Belém, PA, Brasil.
authors: Auriekson N
authors: AN
authors: Queiroz
authors: Amazon Nucleus of Studies and Selection of Biomolecules, Institute of Health Sciences, Federal University of Pará, 66075-110, Belém, PA, Brasil.
authors: Anna P S
authors: APS
authors: Mendes
authors: Postgraduate Program in Neuroscience and Cell Biology, Institute of Biological Sciences, Federal University of Pará, 66075-110, Belém, PA, Brasil.
authors: Sanderson C
authors: SC
authors: Araújo
authors: Amazon Nucleus of Studies and Selection of Biomolecules, Institute of Health Sciences, Federal University of Pará, 66075-110, Belém, PA, Brasil.
authors: Luiz C S
authors: LCS
authors: França
authors: Postgraduate Program in Neuroscience and Cell Biology, Institute of Biological Sciences, Federal University of Pará, 66075-110, Belém, PA, Brasil.
authors: Edna C S
authors: ECS
authors: Franco
authors: Postgraduate Program in Neuroscience and Cell Biology, Institute of Biological Sciences, Federal University of Pará, 66075-110, Belém, PA, Brasil.
authors: Walace G
authors: WG
authors: Leal
authors: Institute of Chemistry of São Carlos, University of São Paulo, CP 780, 13560-970, São Carlos, SP, Brasil.
authors: Albérico B F
authors: ABF
authors: Da Silva
mesh_terms: D000975:Antioxidants / Q000737:chemistry*; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000737:chemistry; D000077553:Edaravone; D008956:Models, Chemical
chemical_list: D000975:Antioxidants; D000077553:Edaravone; D000983:Antipyrine