Tautomerism of 1Methyl Derivatives of Uracil, Thymine, and 5Bromouracil. Is Tautomerism the Basis for the Mutagenicity of 5-Bromouridine?

The Journal of Physical Chemistry B (Impact Factor: 3.3). 06/1998; 102(26):5228-5233. DOI: 10.1021/jp981005+


The tautomerism of the N-1-methylated derivatives of uracil, thymine, and 5-bromouracil has been studied in order to analyze its implications in the mutagenicity of 5-bromouridine. The tautomeric preference in the gas phase was determined by means of state-of-the-art ab initio quantum mechanical calculations. The influence of solvation in water on the tautomerism was examined by using ab initio self-consistent reaction field and Monte Carlo free energy perturbation techniques. Finally, the effect of the DNA environment on the relative stability between tautomers was estimated from Poisson−Boltzmann calculations. The theoretical results indicate that there are no relevant differences in the intrinsic tautomeric preference of the three pyrimidine bases. The canonical oxo form is the main, if not the exclusive, form in the gas phase. Indeed, neither solvation in water nor solvation in the duplex DNA changes sensibly the relative stability between tautomers. Therefore, our results provide a basis for ruling out the involvement of noncanonical enol tautomers as the origin of the mutagenic properties of 5-bromouridine.

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    ABSTRACT: This review summarizes results concerning molecular interactions of nucleic acid bases as revealed by advanced ab initio quantum chemical (QM) calculations published in last few years. We first explain advantages and limitations of modern QM calculations of nucleobases and provide a brief history of this still rather new field. Then we provide an overview of key electronic properties of standard and selected modified nucleobases, such as their charge distributions, dipole moments, polarizabilities, proton affinities, tautomeric equilibria, and amino group hybridization. Then we continue with hydrogen bonding of nucleobases, by analyzing energetics of standard base pairs, mismatched base pairs, thio-base pairs, and others. After this, the nature of aromatic stacking interactions is explained. Also, nonclassical interactions in nucleic acids such as interstrand bifurcated hydrogen bonds, interstrand close amino group contacts, C—H … O interbase contacts, sugar–base stacking, intrinsically nonplanar base pairs, out-of-plane hydrogen bonds, and amino–acceptor interactions are commented on. Finally, we overview recent calculations on interactions between nucleic acid bases and metal cations. These studies deal with effects of cation binding on the strength of base pairs, analysis of specific differences among cations, such as the difference between zinc and magnesium, the influence of metalation on protonation and tautomeric equlibria of bases, and cation–π interactions involving nucleobases. In this review, we do not provide methodological details, as these can be found in our preceding reviews. The interrelation between advanced QM approaches and classical molecular dynamics simulations is briefly discussed. © 2002 Wiley Periodicals, Inc. Biopoly (Nucleic Acid Sci) 61: 3–31, 2002; DOI 10.1002/bip.10048
    Biopolymers 12/2000; 61(1):3 - 31. DOI:10.1002/1097-0282(2001)61:1<3::AID-BIP10048>3.0.CO;2-4 · 2.39 Impact Factor
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    International Journal of Quantum Chemistry 01/2001; 82(1):44 - 52. DOI:10.1002/1097-461X(2001)82:1<44::AID-QUA1020>3.0.CO;2-6 · 1.43 Impact Factor
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