Tautomeric equilibria purines

Section 4.2.1 will be devoted to heterocycles, section 4.2.2 will cover other kinds of protomeric tautomeric equilibria (e.g., enol/ketone, formic acid, formamidine, etc.), and section 4.2.3 will discuss an example of a ring/chain tautomeric equilibrium. The order of presentation will be approximately by increasing molecular weight within each section. A review by Kwiatkowski et al. [267] covers work on formamide, pyridines, pyrimidines, purines, and nucleic... 

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]. 

In all of the above crystal studies, bond lengths and bond angles were found to be similar to those of the corresponding purines. As with all X-ray diffraction work, it can not be assumed that a structure found in an anhydrous crystal would necessarily recur in a hydrated one (which, unfortunately, cannot always be obtained), nor do crystal studies necessarily reflect the tautomeric equilibrium attained in aqueous solution. 

Protonation of the purine anion significantly decreases 7(H8,C4) and 7(H8,C5). This observation points to the tautomeric equilibrium N -H, N -H, present in purine. Based on the values of the three-bond coupling constants and taking the correction factor for a methyl group (0.6 Hz) into account a ratio of 1 1 is obtained for N /N tautomers in D2O solution at laboratory temperature. This indicates that the energy of the two tautomers in water solution is nearly equal. In contrast, the content of the N -H form in DMSO solution has been determined to be 30 and 33% using the values of the 7h8,c4 and 7h8,C5 coupling constants, respectively. 

The tautomeric character of the imidazole system is involved in the synthesis of the related dmg dimetridazole (9.52, 1,2-dimethyl-5-nitroimidazole), which is an effective agent against trichomonal infections in veterinary medicine (Scheme 9.28). The synthesis involves the nitration of 2-methylimidazole to form 2-methyl-5-nitroimidazole (9.50), followed by N-methylation. However, compound 9.50 is involved in tautomeric equilibrium with compound 9.51 (2-methyl-4-nitroimidazole), which would give an isomer (9.53) on methylation. This can be avoided by the proper choice of solvent. Using a nonpolar solvent for methylation with dimethyl sulfate, the desired 9.52 is the predominant product. Tautomerism is a complicating factor in imidazole chemistry where an NH unit is present, and N-alkyl derivatives are more commonly encountered. We will see this factor again with the purines. 

A tautomeric equilibrium in substituted purines at low temperature has been studied by Seckafova et al. Characteristic C, N chemical shifts and vicinal proton-carbon coupling values have allowed the authors to assign particular sets of the signals to the corresponding tautomers and to establish... 

Now purine itself exists in two tautomeric forms (I and II), presumably in a state of equilibrium, but when a hydrogen of the imidazole nucleus ia substituted, the resulting derivative is of one form or the other. In formula I, there are replaceable hydrogen atoms at positions ... 

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... 

Purines and pyrimidines are planar, aromatic, heterocyclic ring systems which absorb ultraviolet light. Formulas (V) and (VI) depict the two tautomeric forms of the purine xanthine which are in equilibrium with one another. Purines and pyrimidines exist predominantly in the keto form in aqueous solution (la). 

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