Thymine tautomeric forms

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,... 

We should note particularly that uracil and thymine are dioxypyrimidines, whereas cytosine is an amino-oxypyrimidine. All three pyrimidines are thus capable of existing in several tautomeric forms (see Section 11.6.2). 

The bases are monocyclic pyrimidines (see Box 11.5) or bicyclic purines (see Section 11.9.1), and all are aromatic. The two purine bases are adenine (A) and guanine (G), and the three pyrimidines are cytosine (C), thymine (T) and uracil (U). Uracil is found only in RNA, and thymine is found only in DNA. The other three bases are common to both DNA and RNA. The heterocyclic bases are capable of existing in more than one tautomeric form (see Sections 11.6.2 and 11.9.1). The forms shown here are found to predominate in nucleic acids. Thus, the oxygen substituents are in keto form, and the nitrogen substituents exist as amino groups. 

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 . ... 

Like cytosine, uracil (or thymine, its 5-methyl derivative) can exist in six tautomeric forms 27-32. A large amount of experimental evidence shows that uracil and thymine have the diketo (dilactam)... 

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. 

Overall NMR and NQR spectroscopy data thus indicate that the diketo structure predominates for uracil, thymine, and their nucleosides or nucleotides. These studies have failed to detect other tautomeric forms of these compounds. 

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... 

Recent, reports351,352 suggested the existence of uracil and thymine as a mixture of tautomeric forms 28 and 32 in aqueous solutions. 

It should be added that Snyder et al.36i have predicted by means of nonempirical calculations that thymine anion 34 should be more stable than 35 in the gas phase by 21 kcal/mole. It is difficult, however, to compare this figure with tautomeric ratios of the thymine anionic forms in aqueous or in dioxan-water solution. 

Table 27. Electronic (E ), repulsion (Er), and molecular (Em) energies (m ev) for the hydrogen-bonded pair adenine-thymine a, in the tautomeric form II...

Mistakes in base incorporation can be made this is largely a result of the transient existence of tautomeric forms of the bases (Chap. 7). If at the instant of insertion of a new nucleotide by DNA polymerase the base in the template shifts to its rare tautomeric form, which has altered base-pairing specificity, an incorrect nucleotide may be added to the chain e.g., one containing guanine instead of adenine opposite the enol form of thymine. 

It is important that we draw certain of the purine and pyrimidine bases in their preferred tautomeric forms. The correct pairings are given early in the chapter. What alternative pairings would be possible with these (minor) tautomers of thymine and guanine Suggest reasons (referring to Chapter 43 if necessary) why the major tautomers are preferred. 

Tautomers are molecules that differ in the position of a hydrogen atom. A tautomeric form of thymine has the structure... 

The tautomeric forms I had copied out of Davidson s book were, in Jerry s opinion, incorrectly assigned. My immediate retort that several other texts also pictured guanine and thymine in the enol form cut no ice with Jerry. Happily he let out that for years organic chemists had been arbitrarily favoring particular tautomeric forms over their alternatives on only the flimsiest of grounds (3). 

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