Biopolym. Cell. 2014; 30(3):239-246.
Molecular Biophysics
Interaction of 2'-deoxyguanosine with cis-2-butene-1,4-dial: Computational approach to analysis of multistep chemical reactions
1, 2Sviatenko L. K., 1, 3Gorb L. G., 3Hovorun D. M., 1Leszczynski J.
  1. Interdisciplinary Center for Nanotoxicity, Department of Chemistry and Biochemistry, Jackson State University
    Jackson, Mississippi 39217, USA
  2. Kirovohrad Volodymyr Vynnychenko State Pedagogical University
    1, Shevchenka Str., Kirovohrad, Ukraine, 25006
  3. State Key Laboratory of Molecular and Cellular Biology
    Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680

Abstract

cis-2-Butene-1,4-dial represents a microsomal metabolite of furan, an industrially important chemical found in cigarette smoke, air pollution, and also in canned or jarred food. It is expected to be a human carcinogen. Aim. Investigation an effect of cis-2-butene-1,4-dial on the 2'-deoxyguanine which is a model of DNA site. Methods. Optimization of reaction species molecular structures, spectral parameters and Gibbs free energy calculations were performed using Gaussian09 program. Systems of differential equations for kinetics generation were solved using Mathcad15 program. Results. The predicted mechanism of the reaction of cis-2-butene-1,4-dial with 2'-deoxyguanine consists of four-step process formation of four diastereomeric primary adducts and further base-mediated five-step transformation of the primary adducts to the secondary one. The reaction kinetics, which allows defining theconcentration change of any reaction species was calculated. Conclusions. Under physiological conditions the interaction between cis-2-butene-1,4-dial and 2'-deoxyguanine leads to the formation of a stable adduct which could be responsible for the furan genotoxicity.
Keywords: furan, DNA, DFT, mechanism, kinetics

References

[1] U. S. Department of Health and Human Services. Public Health Service. National Toxicology Program. Report on carcinogens. Twelfth Edition. Washington, DC, 2011; 499 p.
[2] Exploratory Data on Furan in Food: Individual Food Products. U. S. Food and Drug Administration, 2008.
[3] Chen LJ, Hecht SS, Peterson LA. Identification of cis-2-butene-1,4-dial as a microsomal metabolite of furan. Chem Res Toxicol. 1995;8(7):903-6.
[4] Marinari UM, Ferro M, Sciaba L, Finollo R, Bassi AM, Brambilla G. DNA-damaging activity of biotic and xenobiotic aldehydes in Chinese hamster ovary cells. Cell Biochem Funct. 1984;2(4):243-8.
[5] Gingipalli L, Dedon PC. Reaction of cis- and trans-2-Butene-1,4-dial with 2'-deoxycytidine to form stable oxadiazabicyclooctaimine adducts. J Am Chem Soc. 2001;123(11):2664-5.
[6] Byrns MC, Predecki DP, Peterson LA. Characterization of nucleoside adducts of cis-2-butene-1,4-dial, a reactive metabolite of furan. Chem Res Toxicol. 2002;15(3):373–9.
[7] Byrns MC, Vu CC, Peterson LA. The formation of substituted 1,N6-etheno-2'-deoxyadenosine and 1,N2-etheno-2'-deoxyguanosine adducts by cis-2-butene-1,4-dial, a reactive metabolite of furan. Chem Res Toxicol. 2004;17(12):1607-13.
[8] Sviatenko L, Gorb L, Hovorun D, Leszczynski J. Interaction of 2'-deoxyadenosine with cis-2-butene-1,4-dial: computational approach to analysis of multistep chemical reactions. J Phys Chem A. 2012;116(9):2333-42.
[9] Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, et al. Gaussian 09, Revision A.01, Gaussian Inc., Wallingford, CT, 2009.
[10] Zhao Y, Truhlar DG. Density functionals with broad applicability in chemistry. Acc Chem Res. 2008;41(2):157-67.