A computational study on the reaction between fisetin and 2,2-diphenyl-1-picrylhydrazyl (DPPH)

  • Eduardo N. Maciel
  • Iuri N. Soares
  • Sebastião C. da Silva
  • Gabriel L. C. de SouzaEmail author
Original Paper
Part of the following topical collections:
  1. VII Symposium on Electronic Structure and Molecular Dynamics – VII SeedMol


The strategy of investigating the antioxidant potential of flavonols through the explicit modeling of chemical reactions (initiated to be employed in a previous work from our group) was taken further in this work. Therefore, a theoretical investigation on the reaction between fisetin and 2,2-diphenyl-1-picrylhydrazyl (DPPH) is presented. All the computations were performed using the density functional theory with the B3LYP functional along with the 6-31G(d,p) basis set. Structural, energetic quantities (ΔG and ΔG++), and reaction rates were probed in order to provide information on the antioxidant activity and to explore the contributions of each hydroxyl group to the referred property. According to the results obtained for the thermodynamic properties, fisetin presents antioxidant potential similar to quercetin (behavior that is also observed experimentally). In addition, the order of contribution of each OH group to the antioxidant potential was found to be 4′-ArOH (the most contributor, presenting ΔG = -5.17 kcal/mol) → 3′-ArOH (ΔG = -3.35 kcal/mol) → 3-ArOH (ΔG = -1.64 kcal/mol) → 7-ArOH (ΔG = 7.72 kcal/mol). These observations are in consistent agreement with the outcomes of other computational investigations performed using bond dissociation enthalpies (BDEs) as descriptors for the antioxidant activity. Therefore, the methodology employed in this work can be used as an alternative for probing antioxidant potential of compounds derived from fisetin.

Graphical Abstract

Illustrative scheme of the PES mapping in terms of hydrogen atom transfer from fisetin 3-ArOH to the nitrogen centered DPPH


Antioxidant potential Fisetin DPPH ΔG ΔG++ Density functional theory (DFT) 



This work was funded by the Brazilian agency CNPq (Process number: 306266/2016-4).


  1. 1.
    Yao Y, Lim G, Xie Y, Ma P, Li G, Meng Q, Wu T (2014) Preformulation studies of myricetin: a natural antioxidant flavonoid. Pharmazie 69:19–26PubMedGoogle Scholar
  2. 2.
    Gordon MH, Roedig-Penman A (1998) Antioxidant activity of quercetin and myricetin in liposomes. Chem Phys Lipids 97:79–85CrossRefGoogle Scholar
  3. 3.
    Chobot V, Hadacek F (2011) Exploration of pro-oxidant and antioxidant activities of the flavonoid myricetin. Redox Rep 16:242–247CrossRefGoogle Scholar
  4. 4.
    Nasri I, Chawech R, Girardi C, Mas E, Ferrand A, Vergnolle N, Fabre N, Mezghani-Jarraya R, Racaud-Sultan C (2017) Anti-inflammatory and anticancer effects of flavonol glycosides from Diplotaxis Harra through GSK3 beta regulation in intestinal cells. Pharm Biol 55:124–131CrossRefGoogle Scholar
  5. 5.
    Bell L, Oruna-Concha MJ, Wagstaff C (2015) Identification and quantification of glucosinolate and flavonol compounds in rocket salad (Eruca sativa, Eruca vesicaria and Diplotaxis tenuifolia) by LC-MS: highlighting the potential for improving nutritional value of rocket crops. Food Chem 172:852–861CrossRefGoogle Scholar
  6. 6.
    Grzesik M, Bartosz G, Dziedzic A, Narog D, Namiesnik J, Sadowska-Bartosz I (2018) Antioxidant properties of ferrous flavanol mixtures. Food Chem 268:567–576CrossRefGoogle Scholar
  7. 7.
    Wright JS, Johnson ER, DiLabio GA (2001) Predicting the activity of phenolic antioxidants: theoretical method, analysis of substituent effects, and application to major families of antioxidants. J Am Chem Soc 123:1173–1183CrossRefGoogle Scholar
  8. 8.
    Leopoldini M., Pitarch IP, Russo N, Toscano M (2004) Structure, conformation, and electronic properties of apigenin, luteolin, and taxifolin antioxidants. A first principle theoretical study. J Phys Chem A 108:92–96CrossRefGoogle Scholar
  9. 9.
    Justino GC, Vieira AJSC (2010) Antioxidant mechanisms of quercetin and myricetin in the gas phase and in solution—a comparison and validation of semi-empirical methods. J Mol Model 16:863–876CrossRefGoogle Scholar
  10. 10.
    Mohajeri A, Asemani SS (2009) Theoretical investigation on antioxidant activity of vitamins and phenolic acids for designing a novel antioxidant. J Mol Struct 930:15–20CrossRefGoogle Scholar
  11. 11.
    Sadasivam K, Kumaresan R (2011) Antioxidant behavior of mearnsetin and myricetin flavonoid compounds—a DFT study. Spectrochim Acta A 79:282–293CrossRefGoogle Scholar
  12. 12.
    Nenadis N, Sigalas MP (2008) A DFT study on the radical scavenging activity of maritimetin and related aurones. J Phys Chem A 112:12196–12202CrossRefGoogle Scholar
  13. 13.
    Giacomelli C, Miranda FdaS, Goncalves NS, Spinelli A (2004) Antioxidant activity of phenolic and related compounds: A density functional theory study on the O-H bond dissociation enthalpy. Redox Rep 9:263–269CrossRefGoogle Scholar
  14. 14.
    de Souza GLC, de Oliveira LMF, Vicari RG, Brown A (2016) A DFT investigation on the structural and antioxidant properties of new isolated interglycosidic O-(1→3) linkage flavonols. J Mol Model 22:100–109CrossRefGoogle Scholar
  15. 15.
    Guajardo-Flores D, Serna-Saldivar SO, Gutiérrez-Uribe JA (2013) Evaluation of the antioxidant and antiproliferative activities of extracted saponins and flavonols from germinated black beans (Phaseolus vulgaris L.) Food Chem 141:1497–1503CrossRefGoogle Scholar
  16. 16.
    Mendes RA, e Silva BLS, Takeara R, Freitas RG, Brown A, de Souza GLC (2018) Probing the antioxidant potential of phloretin and phlorizin through a computational investigation. J Mol Model 24:101CrossRefGoogle Scholar
  17. 17.
    Mendes RA, Almeida SKC, Soares IN, Barboza CA, Freitas RG, Brown A, de Souza GLC (2018) A computational investigation on the antioxidant potential of myricetin 3,4′-di-O-α-L-rhamnopyranoside. J Mol Model 24:133CrossRefGoogle Scholar
  18. 18.
    Maciel EN, Almeida SKC, da Silva SC, de Souza GLC (2018) Examining the reaction between antioxidant compounds and 2,2-diphenyl-1-picrylhydrazyl (DPPH) through a computational investigation. J Mol Model 24:218CrossRefGoogle Scholar
  19. 19.
    Trouillas P, Marsal P, Svobovova A, Vostalova J, Gazak R, Hbrac J, Sedmera P, Kren V, Lazzaroni R, Duroux J -L, Walterova D (2008) Mechanism of the antioxidant action of silybin and 2,3-dehydrosilybin flavonolignans: A joint experimental and theoretical study. J Phys Chem A 112:1054–1063CrossRefGoogle Scholar
  20. 20.
    Fezai R, Mezni A, Rzaigui M (2018) Synthesis, structural analysis, Hirshfeld surface, spectroscopic characterization and, in vitro, antioxidant activity of a novel organic cyclohexaphosphate. J Mol Struct 1154:64–71CrossRefGoogle Scholar
  21. 21.
    Yang W, Fortunati E, Bertoglio F, Owczarek JS, Bruni G, Kozanecki M, Kenny JM, Torre L, Visai L, Puglia D (2018) Polyvinyl alcohol/chitosan hydrogels with enhanced antioxidant and antibacterial properties induced by lignin nanoparticles. Carbohydr Polym 181:275–284CrossRefGoogle Scholar
  22. 22.
    Vagánek A, Rimarčik J, Lukeš V, Klein E (2012) On the energetics of homolytic and heterolytic O–H bond cleavage in flavonols. Comput Theor Chem 991:192–200CrossRefGoogle Scholar
  23. 23.
    Marković ZS, Mentus SV, Dimitrić Marković JM (2009) Electrochemical and density functional theory study on the reactivity of fisetin and its radicals: Implications on in vitro antioxidant activity. J Phys Chem A 113:14170–14179CrossRefGoogle Scholar
  24. 24.
    Amić D, Stepanić W, Lučić R, Marković Z, Dmitrić Marković J M (2013) PM6 study of free radical scavenging mechanisms of flavonoids: Why does OH bond dissociation enthalpy effectively represent free radical scavenging activity. J Mol Model 19:2593–2603CrossRefGoogle Scholar
  25. 25.
    Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652CrossRefGoogle Scholar
  26. 26.
    Lee C, Yang W, Parr RG (1988) Development of the Colle–Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37:785–789CrossRefGoogle Scholar
  27. 27.
    Vosko SH, Wilk L, Nusair M (1980) Accurate spin-dependent electron liquid correlation energies for local spin density calculations: A critical analysis. Can J Phys 58:1200–1211CrossRefGoogle Scholar
  28. 28.
    Stephens PJ, Devlin FJ, Chabalowski CF, Frisch MJ (1994) Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields. J Phys Chem 98:11623–11627CrossRefGoogle Scholar
  29. 29.
    Rassolov V, Pople JA, Ratner M, Redfern PC, Curtiss LA (2001) 6-31G* basis set for third-row atoms. J Comp Chem 22:976–984CrossRefGoogle Scholar
  30. 30.
    Binkley JS, Pople JA, Hehre WJ (1980) Self-consistent molecular orbital methods. 21. Small split-valence basis sets for first-row elements. J Am Chem Soc 102:939–946CrossRefGoogle Scholar
  31. 31.
    Rajaraman D, Sundararajan G, Rajkumar R, Bharanidharan S, Krishnasamy K (2016) Synthesis, crystal structure investigation, DFT studies and DPPH radical scavenging activity of 1-(furan-2-ylmethyl)-2,4,5-triphenyl-1H-imidazole derivatives. J Mol Struct 1108:698–707CrossRefGoogle Scholar
  32. 32.
    Miliauskas G, Venskutonis PR, van Beek TA (2004) Screening of radical scavenging activity of some medicinal and aromatic plant extracts. Food Chem 85:231–237CrossRefGoogle Scholar
  33. 33.
    Kumaran A, Karunakaran RJ (2007) In vitro antioxidant activities of methanol extracts of five Phyllanthus species from India. LWT - Food Sci Technol 40:344–352CrossRefGoogle Scholar
  34. 34.
    Mahdi-Pour B, Jothy SL, Latha LY, Chen Y, Sasidharan S (2012) Antioxidant activity of methanol extracts of different parts of Lantana camara. Asian Pac J Trop Biomed 2:960–965CrossRefGoogle Scholar
  35. 35.
    Scalmani G, Frisch MJ (2010) Continuous surface charge polarizable continuum models of solvation. I. General formalism. J Chem Phys 132:114110CrossRefGoogle Scholar
  36. 36.
    Cancès E, Mennucci B, Tomasi J (1997) A new integral equation formalism for the polarizable continuum model: Theoretical background and applications to isotropic and anisotropic dielectrics. J Chem Phys 107:3032–3041CrossRefGoogle Scholar
  37. 37.
    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery Jr. J A, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam NJ, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian, Inc., Wallingford CT, Gaussian 09, Revision D.01Google Scholar
  38. 38.
    Khan NK, Syed DN, Ahmad N, Mukhtar H (2013) Fisetin: a dietary antioxidant for health promotion. Antioxid Redox Signal 19:151–162CrossRefGoogle Scholar
  39. 39.
    Atkins PW, De Paula J Físico−Química, Vol. 2, 9a.Ed., Rio de Janeiro, Brazil, LTCGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Departamento de QuímicaUniversidade Federal de Mato GrossoCuiabáBrazil
  2. 2.Instituto Federal de Educação, Ciência e Tecnologia de Mato GrossoRondonópolisBrazil

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