Purines, hydroxy-, tautomerism

Some of the impetus for studying tautomeric equilibria in heterocycles arises because of the postulate that point mutations in genetic material may be introduced when a given base exists in a tautomeric form during replication [279, 305-307], Cytosine, in particular, has imino and hydroxy tautomers that are within 3 kcal/mol of the global minimum illustrated above (because of the very large number of possible tautomers for the purines and pyrimidines, only the lowest energy tautomers are presented). This analysis has been made based on a... 

The keto/enol or amino/imino equilibrium can be shifted, however, if the bases are chemically modified as in isoguanine (2-hydroxy,4-amino-purine). In this molecule, the tautomeric equilibrium depends largely on the dielectric constant of the solvent [525]. 

Among the species produced upon radiolysis of water, hydroxyl radical ( OH) is the most reactive. Indeed, its reaction rate with the four bases and related nucleosides is diffusion-controlled. The main reactive sites of hydroxyl radicals on nucleobases are the double-bonds of the heterocycles. Accordingly, addition of OH at the C8 position of adenine and guanine yields the corresponding reducing 8-hydroxy-7,8-dihydropurin-7-yl radical (Fig. 2). Oxidation of this intermediate leads to the formation of related 8-hydroxypurines that are in dynamic equilibrium with their more stable 8-oxo-7,8-dihydropurine tautomeric form. Competitive reduction of the latter purine radical gives rise to imidazole ring opened compounds the... 

The second method started from derivatives of 6-mercaptopurines and a-halogeno-alkyl or -aryl or -heteroaryl ketones with conversion to the respective 6-[(acylalkyl)thio]- or 6-[(aroylmethyl)thio]- or 6-[(heteroaroylmethyl)thio]-purines 138 and tautomeric 7-hydroxy-7,8-dihydrothiazolo[2,3-r]-purines 139. The final step of this synthesis was cyclodehydratation. 

The hydroxy derivatives of the diazines exist predominantly in the oxo form where such tautomerism is possible, but, unlike the pyridones, the aromaticity of these compounds has excited rather little attention. In an early paper Pauling and Sherman271 provided extensive data for the resonance energies of a large number of molecules, which included a series of ureides and purines. Inspection of the results shows that a structure such as 4-methyl uracil has substantial excess resonance energy over the sum of the resonance energies for two amide groups (see also Tack 273). 

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