Biopolym. Cell. 2010; 26(4):295-298.
Molecular Biophysics
Stability of mutagenic tautomers of uracil and its halogen derivatives: the results of quantum-mechanical investigation
1, 2Brovarets' O. O., 1, 3Hovorun D. M.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Taras Shevchenko National University of Kyiv
    64/13, Volodymyrska Str., Kyiv, Ukraine, 01601
  3. Institute of High Technologies,
    Taras Shevchenko National University of Kyiv
    2, korp.5, Pr. Akademika Hlushkova, Kyiv, Ukraine, 03022


Aim. To investigate by quantum-mechanical methods the uracil (Ura) intramolecular tautomerisation and effect of changing the thymine (Thy) methyl (Me) group with halogen on this process. Methods. Non-empirical quantum mechanics, analysis of the electron density by means of Bader’s atom in molecules (AIM) theory and physical-chemical kinetics were used. Results. It has been established for the first time that the substitution of halogen (Br, F, Cl) for thymine Me-group has practically no effect on the main physical-chemical characteristics of the intramolecular tautomerisation. At the same time, the energy of Ura tautomerisation increases by 3.08 kcal/mole in comparison with the corresponding value for Thy under standard conditions. Conclusions. Thus, Thy, unlike Ura, is obviously able, as a canonical DNA nucleotide base, to provide together with Ade, Gua and Cyt an acceptable mutability degree of the genom from the point of view of its adaptation reserve. A mutagenic action of the Ura halogen derivatives is not directly associated with their tautomerisation.
Keywords: DNA bases, uracil, mutagenic tautomers, uracil halogenation, lifetime, intramolecular tautomerisation, quantum-mechanical calculations


[1] Brovarets' O. O., Hovorun D. M. How stable are the mutagenic tautomers of DNA bases? Biopolym. Cell 2010 26, N 1:72–76.
[2] Drake J. W., Baltz R. H. The biochemistry of mutagenesis Annu. Rev. Biochem 1976 45:11–37.
[3] Fryxell K. J., Zuckerkandl E. Cytosine deamination plays a primary role in the evolution of mammalian isochores Mol. Biol. Evol 2000 17, N 9:1371–1383.
[4] Litman R. M., Pardee A. B. The induction of mutants of bacteriophage T2 by 5-bromuracile. III. Nutritional and structural evidence regarding mutagenic action Biochim. Biophys. Acta 1960 42:117–130.
[5] Rudner R., Shapiro H., Chargaff E. Distribution of 5-bromouracil among the pyrimidine clusters of the deoxyribonucleotide acid of E. coli Nature 1962 195, N 4837:143– 146.
[6] Kramer G., Wittmann H. G., Schuster H. Die Erzeutung von Mutanten des Tabakmosaikvirus durch den Einbau von Fluorouracil in die Virus-nukleinsaure Z. Naturforsch. B 1964 19:46–51.
[7] Cooper P. D. The mutation of polivirus by 5-fluoruracil Virology 1964 22, N 2:186–192.
[8] Hanus M., Kabela M., Nachtigallova D., Hobza P. Mutagenic properties of 5-halogenuracils: correlated quantum chemical ab initio study Biochemistry 2005 44, N 5:1701– 1707.
[9] Orozco M., Hernandez B., Luque F. J. Tautomerism of 1-methyl derivatives of uracil, thymine, 5-bromouracil. Is tautomerism the basis for the mutagenicity of 5-bromouridine? J. Phys. Chem. B 1998 102, N 26:5228–5233.
[10] Kochina OS, Zhyrakivsky RO, Hovorun DM. Influence of tautomerisation of nucleobases on conformational properties of nucleosides: a quantum-mechanical study withing the method of the density functional theory. Dopovidi Nats Akad Nauk Ukrainy. 2008; (1):181-6.
[11] Inge-Vechtomov S. G. Neodnoznachnost’ matrichnykh protsessov kak faktor adaptatsii Sistemy nadezhnosti kletki. Pod red. D. M. Grodzinskogo Kyiv: Nauk. dumka, 1977 P. 75–85.
[12] Lantsov V. A. DNA repair and carcinogenesis: universal mechanisms for repair in pro- and eukaryotes and consequences of the damage in humans. Mol Biol (Mosk). 1998; 32, N 5 P. 757–772.
[13] Watson J. D., Crick F. H. C. The structure of DNA Cold Spring Harbor Symp. Quant. Biol 1953 18:123–131.