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Density Functional Theory (DFT) Study of Edaravone Derivatives as Antioxidants
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
* Author to whom correspondence should be addressed.
Received: 18 May 2012; in revised form: 9 June 2012 / Accepted: 11 June 2012 / Published: 20 June 2012
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 (∆Eiso). 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 BDECH 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 C2 and C4 positions and there is a correlation between IP and BDE. Our results identified three different classes of new derivatives more potent than edaravone.
Keywords: edaravone derivatives; ionization potential; bond dissociation energies; antioxidant; DFT
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Borges, R.S.; Queiroz, A.N.; Mendes, A.P.S.; Araújo, S.C.; França, L.C.S.; Franco, E.C.S.; Leal, W.G.; da Silva, A.B.F. Density Functional Theory (DFT) Study of Edaravone Derivatives as Antioxidants. Int. J. Mol. Sci. 2012, 13, 7594-7606.
Borges RS, Queiroz AN, Mendes APS, Araújo SC, França LCS, Franco ECS, Leal WG, da Silva ABF. Density Functional Theory (DFT) Study of Edaravone Derivatives as Antioxidants. International Journal of Molecular Sciences. 2012; 13(6):7594-7606.
Borges, Rosivaldo S.; Queiroz, Auriekson N.; Mendes, Anna P. S.; Araújo, Sanderson C.; França, Luiz C. S.; Franco, Edna C. S.; Leal, Walace G.; da Silva, Albérico B. F. 2012. "Density Functional Theory (DFT) Study of Edaravone Derivatives as Antioxidants." Int. J. Mol. Sci. 13, no. 6: 7594-7606.