Comprehensive Study of the Effects of Methylation on Tautomeric Equilibria of Nucleic Acid Bases

Abstract

Minor tautomers of nucleic acid bases can result by intramolecular proton transfer. These rare tautomers could be stabilized through the addition of methyl groups to DNA bases. A comprehensive theoretical study of tautomers of methylated derivatives of guanine, adenine, cytosine, thymine, and uracil was performed. Molecular geometries of all tautomers were obtained at the density functional theory and MP2 levels with the 6-31G(d,p) basis set, and single-point calculations were performed at the CCSD(T)/6-311G(d,p) level. Tautomers obtained by protonation at the preferred protonation site for methylated isolated bases were compared to their nonmethylated counterparts. The effects of methylation on the relative stabilities of nucleic acid base tautomers are also studied and discussed in this work. The results suggest that some sites on the bases may not be mutagenic and may even stabilize the canonical Watson-Crick form. The results also indicate that a number of methylation sites can stabilize the tautomers, suggesting possible mechanisms for mutagenic changes.

Protonation of methyluracils in the gas phase: The particular case of 3-methyluracil

“…Several recent theoretical studies have been dedicated to the effect of methylation on tautomeric equilibria of nucleobases. [33][34][35][36][37] Our work shows that 3-Me-uracil constitutes a particular case in the series of pyrimidine nucleobases we have studied so far. IRMPD spectroscopy experiments have been performed using an experimental platform employing a quadrupole ion trap (Bruker Esquire 3000+) which has been previously described in detail.…”

Combinations of Tautomeric Forms and Neutral-Cationic Forms in the Cocrystals of Sulfamethazine with Carboxylic Acids

“…Infrared spectra of the solid samples were recorded on a PerkinElmer Spectrum-One FT-IR spectrophotometer in the region 4000−400 cm −1 by making KBr pellets. 1 H NMR spectra of sulfamethazine and the cocrystals were recorded on a Bruker Ascend-600 MHz NMR spectrometer using TMS as internal standard. DSC and thermogravimetry studies were performed using a thermal analyzer SDTQ600 simultaneous DTA/TGA system under nitrogen with a heating rate of 5 °C/min.…”

“…The tautomeric forms of organic compounds are well known to modulate reactivity and physical properties. 1−6 Amidine–imidine equilibriums in solution have impacts on excited-state proton transfer processes in emission spectroscopy. 7−10 Amidine–imidine equilibrium plays an important role in stabilization of a particular tautomer of DNA base-pairs 11−13 such as in cytosine.…”

“…The tautomeric forms of organic compounds are well known to modulate reactivity and physical properties. − Amidine–imidine equilibriums in solution have impacts on excited-state proton transfer processes in emission spectroscopy. − Amidine–imidine equilibrium plays an important role in stabilization of a particular tautomer of DNA base-pairs − such as in cytosine . Large numbers of organic compounds show amidine–imidine equilibrium. − Such equilibriums are studied by various spectroscopic techniques such as nuclear magnetic resonance, infrared spectroscopy, , mass spectrometry, and in solid by X-ray crystal structure determination .…”

Pairing strength and proton characters of the N7,N9-dimethylated GC and AT base pairs: a density functional theory investigation

“…In purine-pyrimidine base pairs, the enhanced acidification of purine will increase the possibility of deprotonation or proton transfer between bases and thus greatly change the proton characters of interacting bases through polarization. Previous studies have mainly centered on mutagenesis, 24 tautomerization of N7-methylation purine 25 and the reactivity of methane diazonium ions with purine. 26 Also, a number of theoretical studies have focused on the effect of metal ions on the H-bond strength of base pairs and proton transfer in base pairs [27][28][29][30][31][32] or the H-bond strength between the natural bases.…”