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Mechanisms of the hydroxyl and superoxide anion radical scavenging activity and protective effect on lipid peroxidation of thymoquinone: a DFT study

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Abstract

The mechanism of thymoquinone (2-isopropyl-5-methyl-1,4-benzoquinone) for scavenging peroxide radicals was explicated in gas phase and in liquid phase (benzene, water) using density functional theory approach. The calculated bond dissociation enthalpy, ionization potential, and proton dissociation enthalpy revealed that the H-atoms at positions 2-isopropyl and 5-methyl groups can be readily abstracted. In fact, the 2-isopropyl C–H bond dissociation enthalpy is lower than the 5-methyl C–H dissociation enthalpy. Analysis of spin density distribution indicates that H-atom abstraction in 2-isopropyl site generates more stable radical. The plots of highest occupied molecular orbital of thymoquinone demonstrate that the whole molecule can be easily attacked by electrophilic agents like radicals. In this paper, we studied the interaction of thymoquinone with hydroxyl, hydroperoxyl, and superoxide anion radicals, using potential energy surface scans and natural bond orbital analysis. Calculated potential energy barriers for hydroxyl radical attack (~2.5 kJ/mol) revealed an instant scavenging by thymoquinone. Modeling of the reaction between thymoquinone and lipid peroxyl radical shows a barrier energy around 26.23 kJ/mol.

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Authors and Affiliations

  1. Department of Physics, University of Kurdistan, P.O.Box 416, Sanandaj, Iran

    Keivan Akhtari & Ghazal Akhtari

  2. Institute of Education Research of Kurdistan Province, Sanandaj, Iran

    Keivan Akhtari, Bahareh Fakhraei & Ghazal Akhtari

  3. Young Researchers and Elites Club, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran

    Keyumars Hassanzadeh

  4. Department of Physics, Tarbiat Modarres University, P.O. Box 14115-175, Tehran, Iran

    Bahareh Fakhraei

  5. Brain and Spinal Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

    Nahid Fakhraei

  6. Biology Department, Science and Research Branch, Islamic Azad University, Sanandaj, Iran

    Halaleh Hassanzadeh

  7. Chemistry Department, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran

    Seyed Amir Zarei

  8. Department of Physiology and Pharmacology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Katayoun Hassanzadeh

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  1. Keivan Akhtari
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  6. Ghazal Akhtari
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Correspondence to Keivan Akhtari or Keyumars Hassanzadeh.

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Akhtari, K., Hassanzadeh, K., Fakhraei, B. et al. Mechanisms of the hydroxyl and superoxide anion radical scavenging activity and protective effect on lipid peroxidation of thymoquinone: a DFT study. Monatsh Chem 146, 601–611 (2015). https://doi.org/10.1007/s00706-014-1341-3

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  • DOI: https://doi.org/10.1007/s00706-014-1341-3

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