Tautomerism of 1-Methyl Derivatives of Uracil, Thymine, and 5-Bromouracil. Is Tautomerism the Basis for the Mutagenicity of 5-Bromouridine?
Citations Over TimeTop 16% of 1998 papers
Abstract
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.
Related Papers
- → Partial Molar Volumes of Uracil, Thymine, Adenine in Water and of Adenine in Aqueous Solutions of Uracil and Thymine(2008)12 cited
- Effect of coadministration of thymine or thymidine on the antitumor activity of 1-(2-tetrahydrofuryl)-5-fluorouracil and 5-fluorouracil.(1980)
- → Synthetic pyrimidines as inhibitors of uracil and thymine degradation by rat-liver supernatant(1964)22 cited
- → Synthesis of polyacrylic and polymethacrylic derivatives having pendant uracil and thymine moieties(1980)9 cited
- → THE EFFECTS OF URIDINE AND THYMIDINE ON THE DEGRADATION OF 5-FLUOROURACIL (5-FU), URACIL AND THYMINE BY RAT LIVER DIHYDROPYRIMIDINE DEHYDROGENASE (DPD): 213(1985)1 cited