ORIGINAL PAPER Mechanisms of the hydroxyl and superoxide anion radical scavenging activity and protective effect on lipid peroxidation of thymoquinone: a DFT study Keivan Akhtari • Keyumars Hassanzadeh • Bahareh Fakhraei • Nahid Fakhraei • Halaleh Hassanzadeh • Ghazal Akhtari • Seyed Amir Zarei • Katayoun Hassanzadeh Received: 31 May 2014 / Accepted: 18 October 2014 Ó Springer-Verlag Wien 2014 Abstract The mechanism of thymoquinone (2-isopropyl- 5-methyl-1,4-benzoquinone) for scavenging peroxide rad- icals 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 gen- erates 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 interac- tion of thymoquinone with hydroxyl, hydroperoxyl, and superoxide anion radicals, using potential energy surface scans and natural bond orbital analysis. Calculated poten- tial 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. Keywords Density functional theory  Thymoquinone  Hydroxyl radical  Superoxide anion radical  Lipid peroxidation K. Akhtari (&)  G. Akhtari Department of Physics, University of Kurdistan, P.O.Box 416, Sanandaj, Iran e-mail: k1akhtari@yahoo.com K. Akhtari  B. Fakhraei  G. Akhtari Institute of Education Research of Kurdistan Province, Sanandaj, Iran K. Hassanzadeh (&) Young Researchers and Elites Club, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran e-mail: keyumars_hassanzadeh@yahoo.com B. Fakhraei Department of Physics, Tarbiat Modarres University, P.O. Box 14115-175, Tehran, Iran N. Fakhraei Brain and Spinal Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran H. Hassanzadeh Biology Department, Science and Research Branch, Islamic Azad University, Sanandaj, Iran S. A. Zarei Chemistry Department, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran K. Hassanzadeh Department of Physiology and Pharmacology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran 123 Monatsh Chem DOI 10.1007/s00706-014-1341-3