Molecular modeling and thermodynamics of the interaction between DNA base pairs and radon originated ionizing alpha radiation

Abstract

Ionizing alpha radiation (He2+) is known to adversely affect human DNA, but the biochemical reasoning is not clear yet. Relatedly, the present computational study was conducted investigating the effects of ionizing alpha radiation onto the Watson-Crick type DNA base pairs (nucleotides) Adenine-Thymine (AT’) and Guanine-Cytosine (GC’). The long-range cation (He2+)−π interactions were modeled for this purpose. A hybrid DFT functional of M06-2X was used with 6-31G(d,p) and 6-311G(d) basis sets at unrestricted level. The results showed that alpha radiation severely changed the considered base pairs’ hydrogen bond lengths and their interaction enthalpies and Gibbs free energies, however, the more drastic changes were observed in GC’ rather than AT’. This observation was also supported by frontier molecular orbital analyses performed. GC’ was more favored to form He2+ complexes (oxidize) than AT’ and consequently these complexes had more exothermic interaction energies (formed more spontaneously) than that of AT’. It could be highlighted that the molecular modeling proposed in this study would contribute to the elucidation of the uncertainty in this field.

Keywords

• DNA base pairs
• alpha radiation
• interaction enthalpy
• interaction Gibbs free energy
• M06-2X

References

1. Bale WF. 1980. Memorandum to the files, March 14, 1951: hazards associated with radon and thoron. Health Phys. 38(6):1062-1066
2. Boys SF, Bernardi F. 1970. The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol. Phys. 19(4):553-566.
3. Brameld K, Dasgupta S, Goddard WA. 1997. Distance dependent hydrogen bond potentials for nucleic acid base pairs from ab initio quantum mechanical calculations (LMP2/cc-pVTZ). J. Phys. Chem. B 101(24):4851-4859
4. Chen DJ, Strniste GF, Tokita N. 1984. The genotoxicity of alpha particles in human embryonic skin fibroblasts. Radiat. Res. 100(2):321-327.
5. Davis MR, Dougherty DA. 2015. Cation-π interactions: computational analyses of the aromatic box motif and the fluorination strategy for experimental evaluation. Phys. Chem. Chem. Phys. 17(43):29262-29270.
6. Dhindhwal V, Sathyamurthy N. 2016. The effect of hydration on the cation-π interaction between benzene and various cations. J. Chem. Sci. 128(10):1597-1606.
7. Durrani SA, Ilić R. 1997. Radon measurements by etched track detectors: applications in radiation protection, earth sciences and the environment. World Scientific, Singapore, New Jersey, London, Hong Kong.
8. Ebrahimi A, Karimi P, Akher FB, Behazin R, Mostafavi N. 2014. Investigation of the π-π stacking interactions without direct electrostatic effects of substituents: the aromatic∥aromatic and aromatic∥anti-aromatic complexes. Mol. Phys. 112(7):1047-1056.

9. Guerra CF, Bickelhaupt FM, Snijders JG, Baerends EJ. 2000. Hydrogen bonding in DNA base pairs: reconciliation of theory and experiment. J. Am. Chem. Soc. 122(17):4117-4128.
10. Harley JH. 1952. Sampling and measurement of airborne daughter products of radon [dissertation]. Rensselaer Polytechnic Institute, Troy (NY).
11. Hollstein M, Bartsch H, Wesch H, Kure EH, Mustonen R, Mühlbauer KR, Spiethoff A, Wegener K, Wiethege T, Müller KM. 1997. p53 gene mutation analysis in tumors of patients exposed to alpha-particles. Carcinogenesis 18(3):511-516.
12. Koopmans T. 1934. Über die zuordnung von wellenfunktionen und eigenwerten zu den einzelnen elektronen eines atoms. Physica 1(1-6):104-113.
13. McDonald JW, Taylor JA, Watson MA, Saccomanno G, Devereux TR. 1995. p53 and K-ras in radon-associated lung adenocarcinoma. Cancer Epidemiol., Biomarkers Prev. 4(7):791-793.
14. Mo, Y. 2006. Probing the nature of hydrogen bonds in DNA base pairs. J. Mol. Model. 12(5):665-672.
15. Mottishaw JD, Sun H. 2013. Effects of aromatic trifluoromethylation, fluorination, and methylation on intermolecular π-π interactions. J. Phys. Chem. A 117(33):7970-7979.
16. Mudedla SK, Balamurugan K, Subramanian V. 2014. Computational study on the interaction of modified nucleobases with graphene and doped graphenes. J. Phys. Chem. C 118(29):16165-16174.
17. Narayanan PK, Goodwin EH, Lehnert BE. 1997. Alpha particles initiate biological production of superoxide anions and hydrogen peroxide in human cells. Cancer Res. 57(18):3963-3971.
18. National Radiological Protection Board. 1998. Living with radiation. NRPB, London.
19. Parr RG, Szentpály LV, Liu S. 1999. Electrophilicity index. J. Am. Chem. Soc. 121(9):1922-1924.
20. Pearson RG. 1997. Chemical hardness. Wiley-VCH, Weinheim, New York (NY).
21. Popp W, Vahrenholz C, Schuster H, Wiesner B, Bauer P, Täuscher F, Plogmann H, Morgenroth K, Konietzko N, Norpoth K. 1999. p53 mutations and codon 213 polymorphism of p53 in lung cancers of former uranium miners. J. Cancer Res. Clin. Oncol. 125(5):309-312.
22. Raya A, Barrientos-Salcedo C, Rubio-Póo C, Soriano-Correa C. 2011. Electronic structure evaluation through quantum chemical descriptors of 17β-aminoestrogens with an anticoagulant effect. Eur. J. Med. Chem. 46(6):2463-2468.
23. Robertson A, Allen J, Laney R, Curnow A. 2013. The cellular and molecular carcinogenic effects of radon exposure: a review. Int. J. Mol. Sci. 14(7):14024-14063.
24. Rokhina EV, Suri RPS. 2012. Application of density functional theory (DFT) to study the properties and degradation of natural estrogen hormones with chemical oxidizers. Sci. Total Environ. 417-418:280-290.
25. Saenger W. 1984. Principles of nucleic acid structure. Springer-Verlag, New York (NY).
26. Singh PP, Srivastava HK, Pasha FA. 2004. DFT-based QSAR study of testosterone and its derivatives. Bioorg. Med. Chem. 12(1):171-177.
27. Soğukpınar H. 2013. Determination of seasonal correction factors for indoor radon concentrations in Eskisehir [dissertation]. Eskişehir Osmangazi University, Eskişehir, Turkey.
28. Spartan’18 Parallel Suite. 2018. Wavefunction, Inc., Irvine (CA).
29. Srivastava HK, Pasha FA, Mishra SK, Singh PP. 2009. Novel applications of atomic softness and QSAR study of testosterone derivatives. Med. Chem. Res. 18(6):455-466.
30. Taylor JA, Watson MA, Devereux TR, Michels RY, Saccomanno G, Anderson M. 1994. p53 mutation hotspot in radon-associated lung cancer. Lancet 343(8889):86-87.
31. Wazer DE, Chu Q, Liu XL, Gao Q, Safaii H, Band V. 1994. Loss of p53 protein during radiation transformation of primary human mammary epithelial cells. Mol. Cell. Biol. 14(4):2468-2478.
32. Wesch H, Wiethege T, Spiethoff A, Wegener K, Müller KM, Mehlhorn J. 1999. German uranium miner study: historical background and available histopathological material. Radiat. Res. 152(6s):S48-S51.
33. Wiethege T, Wesch H, Wegener K, Müller KM, Mehlhorn J, Spiethoff A, Schömig D, Hollstein M, Bartsch H. 1999. German uranium miner study: pathological and molecular genetic findings. Radiat. Res. 152(6s):S52-S55.
34. Yang Q, Wesch H, Mueller KM, Bartsch H, Wegener K, Hollstein M. 2000. Analysis of radon-associated squamous cell carcinomas of the lung for a p53 gene hotspot mutation. Br. J. Cancer 82(4):763-766.
35. Yanson IK, Teplitsky AB, Sukhodub LF. 1979. Experimental studies of molecular interactions between nitrogen bases of nucleic acids. Biopolymers 18(5):1149-1170.
36. Zeeb H, Shannoun F. 2009. WHO handbook on indoor radon: a public health perspective. World Health Organization, France.
37. Zhao Y, Truhlar DG. 2008. Density functionals with broad applicability in chemistry. Acc. Chem. Res. 41(2):157-167