Uracil tautomeric forms

Azauracil and its alkyl derivatives are readily reducible by polarography, in contrast with uracil. This makes it possible to exploit the method analytically. More detailed studies of the polaro-graphic behavior of these substances are in good agreement with the results of spectral studies about the tautomeric form and type of dissociation. ... 

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 . ... 

FIGURE 8-9 Tautomeric forms of uracil. The lactam form predominates at pH 7.0 the other forms become more prominent as pH decreases. The other free pyrimidines and the free purines also have tautomeric forms, but they are more rarely encountered. 

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)... 

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. 

X-Ray results are available for the molecular structures of nearly all rare pyrimidine constituents of the nucleic acids except for isothiocyto-sine. Thio analogs of uracil exist in the tautomeric form of the 32 type ... 

Cytosine, uracil, and guanine have tautomeric forms with aromatic hydroxyl groups. Draw these tautomeric forms. 

Fig. 15.4. Keto/enol and amino/imino tautomeric forms of uracil, cytosine, adenine, guanine. The keto and amino forms predominate, the enol and imino forms are only present in equilibrium at 0.01 Vo or less...

Calometric measurements of the heat isomerization in liquid were used to determine the relative gas-phase enthalpies of fixed derivatives of uracil and provided estimates of the enthalpy difference between the dioxo form and other tautomers of uracil in vapor (19 6kcal/mol for 158c and 22+ lOkcal/mol for 158d) (82JA7073). N -Substituted uracils were shown to exist in the dioxo tautomeric form in the vapor (78ZN(C)876). 

The effects of complexation with metals on tautomerism of neutral and anionic uracils have been reviewed (87CCR97). Interestingly, complexation of 1-methyl-uracil (89JA7213) or 1-methylthymine (81ICA(55)5) with neutral platinum complexes stabilizes the rare 2-oxo-4-hydroxy tautomeric forms. 

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