Thymine tautomers

TABLE 7.17 Relative Energies (in Real mol ) of Thymine Tautomers (5a-my... 

Morsy, M. A. Al-Somali, A. M. Suwaiyan, A. Fluorescence of thymine tautomers at room temperature in aqueous solutions, 7. Phys. Chem. B 1999,103, 11205-11210. 

However, the thymine tautomers, with lack of correlation between HOMA index and relative energies of the tautomers, are an instructive... 

Figure 3 Dependence of HOMA on relative energy, rei, for thymine tautomers. Group (a) blue (black In print versions) circles, (b) red (light gray in print versions) diamonds, and (c) crosses. HOMA, harmonic oscillator model of aromaticity. Reproduced by permission of The Royal Society of Chemistry from Stasyuk et al. (2014OBC6476).

Figure 4 Structures of the most stable thymine tautomers and natural bond orbital atomic charges.

Uracil, thymine, and cytosine have been studied using this technique (89JA2308 and references therein). For uracil and thymine, the dioxo tautomer predominates in the case of cytosine (70), three tautomers were detected, 70a, 70b, and 70c, the last one being the least abundant. The gas-phase tautomeric equilibrium of 2-pyridone 15a and 2-hydroxypyridine 15b has been studied by MW spectroscopy (93JPC46) using both a conventional spectrometer and a jet-cooled millimeter-wave spectrometer. The relative abundances are 3 1 in favor of the hydroxy form 15b, which exists in the Z conformation shown (Scheme 23). 

The tautomerisation of the purine bases adenine and guanine and of the pyrimidine bases thymine, cytosine, and uracil has important implications in molecular biology, and the occurrence of rare tautomeric forms of these bases has been suggested as a possible cause of spontaneous mutagenesis (Lowdin, 1965 Pullman and Pullman, 1971 Kwiatowski and Pullman, 1975). Three of the most likely tautomers for cytosine are shown in [87]—[89], together with the less likely imino forms [90] and [91] (Scanlan and Hillier,... 

The Mg+ complexes of cytosine, thymine and uracil are the most complex system studied via photodissociation spectroscopy to date . A complication for these systems is that these nucleobases can exist in various tautomeric forms and that complexation of a metal can change the stability order of the tautomers. DFT calculations located four tautomeric Mg(cytosine)+ complexes, and three of these (29, 30, and 31) were suggested to be responsible for the four reactive photofragment ions 32-35 observed at a wavelength of 360 nm (Scheme 4) . Related photofragmentation reactions were observed for the Mg(thymine)+" and Mg(uracil)+" complexes . ... 

Wierzchowski et al.325 recorded in aqueous medium the IR specta of the monoanions of thymine and of 1-methyl- and 3-methylthymine. The data demonstrated that the monoanions of thymine consist of an equilibrium mixture of two tautomeric forms 34 and 35 corresponding to the dissociation of the N-l or the N-3 protons, respectively. The fractional content of the thymine monoanion 35 in the mixture of the two monoanions was evaluated from the extinction of the characteristic bands of the anion of thymine and 1-methylthymine to be 0.4. A marked shift in equilibrium of the tautomers was observed on going from a NaCO in D20 solution of thymine to NaOD in 75% dioxan-D20. Calculation of the tautomeric equilibrium showed that in 75% dioxan the fraction of 35 was 0.25, compared to 0.4 in aqueous medium. 

Starting from the comparative study of the ionization constants of uracil itself as well as of its several methylated or ethylated derivatives (representing models of tautomeric forms), it may be seen (Table XVII) that uracil and uridine exist in aqueous solution in the diketo form 32. The pX values are not known for the model tautomers 27, 29, and 30, but these forms have been ruled out on the basis of UV studies. Recently the ionization constants of uracil, thymine, their derivatives and nucleotides were determined over the range 10-50°, and thermodynamic enthalpy, entropy, and free energy changes for protonation and depro-tonation of these compounds have been evaluated.93-95,332... 

As the removal of a proton from thymine results in the establishment of a tautomeric equilibrium between its two monoanionic forms,3425 the emission spectrum of singly ionized thymine may consist of overlapping spectra of both monoanions. In fact, Gill344 has observed some inconsistencies between the absorption and the fluorescence excitation spectra of thymine in 0.01 N NaOH at room temperature. These inconsistencies were of the same kind as those found later by Berens and Wierzchowski,345 who suggested that at room temperature only the thymine monoanion tautomer (34) fluoresced, while at 77°K emissions of both monoanionic species contributed to the observed luminescence spectrum. 

Daniels352 has shown that the excitation spectra for triplet state formation and fluorescence emission from uracil and thymine in neutral aqueous solution at room temperature were anomalous when compared with the UV absorption spectra of these pyrimidines. These experimental facts have been critically examined with respect to three molecular models, of which the model based on tautomerism of uracil in aqueous solution is, in the opinion of Daniels, the best. The data suggested that the fluorescing tautomer contained an enol group, and the UV data favored the 4-hydroxy structure, i.e., form 28. The second tautomer, from which the triplet originated, was expected to be the predominant diketo form (32). 

As mentioned previously (Section III) IR and Raman spectroscopic studies have been carried out to elucidate the structure of the main tautomers of uracil and thymine. Although the vibrational spectra of the pyrimidine bases (e.g., refs 41, 50, 51, 55, 326, 354, 370) are difficult to interpret, a better understanding of the vibrational motions of these molecules has been possible over the past years.193,370-372 There have also been some quantum-mechanical attempts to interpret the vibrational spectra. 

Naumov S, Beckert D (2002) Reply to the Comment on A Fourier transform EPR study of uracil and thymine radical anions in aqueous solution)/ by DM Close. Phys Chem Chem Phys 4 45 Naumov S, Barthel A, Reinhold J, Dietz F, Geimer J, Beckert D (2000) Calculation of spin densities of radicals of pyrimidine-type bases by density functional theory. Influence of solvent and comparison with EPR results. Phys Chem Chem Phys 2 4207-4211 Naumov S, Hildenbrand K, von Sonntag C (2001) Tautomers of the N-centered radical generated by reaction of SO4 - with N(1)substituted cytosines in aqueous solution. Calculation of isotropic hyperfine coupling constants by a density functional method. J Chem Soc Perkin Trans 2 1648-1653... 

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