DFT Study on Reaction Mechanism of DNA Base Pair with Hydroxyl Radical


In order to elucidate the indirect effect by radiation on DNA base pairs, we investigate the mechanism for the attacking reaction of a hydroxyl radical (·OH-radical) to the G-C and A-T base pairs, by the density functional theory (DFT) calculations. The effect of solvation on the mechanism is also revealed by performing the same DFT calculations under the continuum solvation approximation. We find the stable structures for the dehydrogenated G-C and A-T base pairs, in which the hydrogen atom of NH2 group of G or A base is abstracted by the ·OH-radical. The solvation around the base pairs stabilizes the dehydrogenated structures significantly, indicating the acceleration of the attacking reaction by ·OH-radical to the base pairs in water. Therefore, we conclude that the hydrogen atom of the NH2 group of G or A base in the G-C and A-T base pairs is the most preferably abstracted by the ·OH-radical in living cells.

Share and Cite:

E. Shimizu, R. Hoshino, K. Nomura, V. Danilov and N. Kurita, "DFT Study on Reaction Mechanism of DNA Base Pair with Hydroxyl Radical," Journal of Modern Physics, Vol. 4 No. 3A, 2013, pp. 442-451. doi: 10.4236/jmp.2013.43A062.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] T. Douki and J. Cadet, “Radiation-Induced Damage to DNA: From Model Compounds to Cell,” In: M. Spotheim-Maurizot, M. Mostafavi, T. Douki and J. Belloni, Eds., Radiation Chemistry: From Basics to Applications in Material and Life Sciences, EDP Sciences, Les Ulis Cedex A, 2008, pp. 177-189.
[2] D. Khanduri, S. Collins, A. Kumar, A. Adhikary and M. D. Sevilla, “Formation of Sugar Radicals in RNA Model Systems and Oligomers via Excitation of Guanine Cation Radical,” Journal of Physical Chemistry B, Vol. 112, No. 7, 2008, pp. 2168-2178. doi:10.1021/jp077429y
[3] J. Cadet, T. Douki and J.-L. Ravanat, “Oxidatively Generated Base Damage to Cellular DNA,” Free Radical Biological Medicine, Vol. 49, No. 1, 2010, pp. 9-21. doi:10.1016/j.freeradbiomed.2010.03.025
[4] J. R. Wagner and J. Cadet, “Oxidation Reactions of Cytosine DNA Components by Hydroxyl Radical and One-Electron Oxidants in Aerated Aqueous Solutions,” Accounts of Chemical Research, Vol. 43, No. 4, 2010, pp. 564-571. doi:10.1021/ar9002637
[5] B. Aydogan, W. E. Bolch, S. G. Swarts, J. E. Turner and D. T. Marshall, “Monte Carlo Simulations of Site-Specific Radical Attack to DNA Bases,” Radiation Research, Vol. 169, No. 2, 2008, pp. 223-231. doi:10.1667/RR0293.1
[6] H. Sies, “Strategies of Antioxidant Defense,” European Journal of Biochemistry, Vol. 215, No. 2, 1993, pp. 213-219. doi:10.1111/j.1432-1033.1993.tb18025.x
[7] M. S. Cooke, M. D. Evans, M. Dizdaroglu and J. Lunce, “Oxidative DNA Damage: Mechanisms, Mutation, and Disease,” FASEB Journal, Vol. 17, No. 10, 2003, pp. 1195-1214. doi:10.1096/fj.02-0752rev
[8] H. Tomita, M. Kai, T. Kusama and A. Ito, “Monte Carlo Simulation of DNA Strand-break Induction in Supercoiled Plasmid pBR322 DNA from Indirect Effects,” Radiation and Environmental Biophysics, Vol. 36, No. 4, 1998, pp. 235-241. doi:10.1007/s004110050077
[9] R. M. Abolfath, A. C. T. van Duin and T. Brabec, “Reactive Molecular Dynamics Study on the First Steps of DNA Damage by Free Hydroxyl Radicals,” Journal of Physical Chemistry A, Vol. 115, No. 40, 2011, pp. 11045-11049. doi:10.1021/jp204894m
[10] C. J. Mundy, M. E. Colvin and A. A. Quong, “Irradiated Guanine: A Car-Parrinello Molecular Dynamics Study of Dehydrogenation in the Presence of an OH Radical,” Journal of Physical Chemistry A, Vol. 106, No. 43, 2002, pp. 10063-10071. doi:10.1021/jp0212904
[11] A. Kumar, V. Pottiboyina and M. D. Sevilla, “Hydroxyl Radical (OH) Reaction with Guanine in an Aqueous Environment: A DFT study,” Journal of Physical Chemistry B, Vol. 115, No. 50, 2011, pp. 15129-15137. doi:10.1021/jp208841q
[12] R. M. Abolfath, P. K. Biswas, R. Rajnarayanam, T. Brabec, R. Kodym and L. Papiez, “Multiscale QM/MM Molecular Dynamics Study on the First Steps of Guaninedamage by Free Hydroxyl Radicals in Solution,” Journal of Physical Chemistry A, Vol. 116, No. 15, 2012, pp. 3940-3945. doi:10.1021/jp300258n
[13] J. P. Ceron-Carrasco and D. Jacquemin, “Interplay between Hydroxyl Radical Attack and H-bond Stability in Guanine-Cytosine,” RSC Advances, Vol. 2, No. 31, 2012, pp. 11867-11875. doi:10.1039/c2ra22389a
[14] R. B. Zhang and L. A. Eriksson, “Effects of OH Radical Addition on Proton Transfer in the Guanine-Cytosine Base Pair,” Journal of Physical Chemistry B, Vol. 111, No. 23, 2007, pp. 6571-6576. doi:10.1021/jp071772l
[15] Q. Cheng, J. Gu, K. R. Compaan and H. F. Schaefer III, “Hydroxyl Radical Reactions with Adenine: Reactant Complexes, Transition States, and Product Complexes,” Chemistry—A European Journal, Vol. 16, No. 39, 2010, pp. 11848-11858. doi:10.1002/chem.201001236
[16] Y. Maruyama, M. Tachikawa and S. Kawano, “Ab Initio Study of DNA Double-Strand Breaks by Hydroxyl Radicals,” Japanese Society Mechanism Enginering International Journal B, Vol. 48, 2005, pp. 196-201.
[17] B. Delley, “An All Electron Numerical Method for Solving the Local Density Functional for Polyatomic Molecules,” Journal of Chemical Physics, Vol. 92, No. 1, 1990, pp. 508-517. doi:10.1063/1.458452
[18] B. Delley, “From Molecules to Solids with the DMol3 Approach,” Journal of Chemical Physics, Vol. 113, No. 18, 2000, pp. 7756-7764. doi:10.1063/1.1316015
[19] J. Perdew, K. Burke and M. Ernzerhof, “Generalized Gadient Aproximation Made Simple,” Physical Review Letters, Vol. 77, 1996, pp. 3865-3868. doi:10.1103/PhysRevLett.77.3865
[20] A. D. Becke, “Density-Functional Thermochemistry. III. The Role of Exact Exchange,” Journal of Chemical Physics, Vol. 98, No. 7, 1993, pp. 5648-5652. doi:10.1063/1.464913
[21] M. J. Frisch, et al., “Gaussian 09,” Gaussian, Inc., Wallingford, 2009.
[22] M. J. Lundqvist and L. A. Eriksson, “Hydroxyl Radical Reactions with Phenol as a Model for Generation of Biologically Reactive Tyrosyl Radicals,” Journal of Physical Chemistry B, Vol. 104, No. 4, 2000, pp. 848-855. doi:10.1021/jp993011r
[23] B. Delley, “The Conductor-like Screening Model for Polymers and Surfaces,” Molecular Simulation, Vol. 32, No. 2, 2006, pp. 117-123. doi:10.1080/08927020600589684
[24] S. Arnott and D. W. L. Hukins, “Refinement of the Structure of B-DNA and Implication for the Analysis of the X-Ray Diffraction Data from Fibers of Biopolymers,” Journal of Molecular Biology, Vol. 81, No. 2, 1973, pp. 93-105. doi:10.1016/0022-2836(73)90182-4
[25] C. Chatgilialoglu, M. D’Angelantonio, M. Guerra, P. Kaloudis and Q. G. Mulazzani, “A Reevaluation of the Ambident Reactivity of the Guanine Moiety Towards Hydroxyl Radicals,” Angewandte Chemie International Edition, Vol. 48, No. 12, 2009, pp. 2214-2217. doi:10.1002/anie.200805372
[26] S. Steenken, “Purine Bases, Nucleosides, and Nucleotides: Aqueous Solution Redox Chemistry and Transformation Reactions of Their Radical Cations and e- and OH Adducts,” Chemical Reviews, Vol. 89, No. 3, 1989, pp. 503-520. doi:10.1021/cr00093a003?
[27] A. J. S. C. Vieira and S. Steenken, “Pattern of Hydroxy Radical Reaction with Adenine and Its Nucleosides and Nucleotides. Characterization of Two Types of Isomeric Hydroxy Adduct and Their Unimolecular Transformation Reactions,” Journal of the American Chemical Society, Vol. 112, No. 19, 1990, pp. 6986-6994. doi:10.1021/ja00175a036

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.