Bond Cooperativity Enhances Hydrogen-Bonding Forces

Theoretically, the purine- and pyrimidine-based nucleic acid constituents and the barbiturates have the potential to occur in several tautomeric forms of the keto/ enol and amino/imino type where the aromatic character of the six-membered pyrimidine ring is fully or, as in the barbiturates, partially retained, as illustrated in Fig. 15.4. In these molecular species, which are all feasible on the basis of organic chemical considerations, the hydrogen-bonding donor/acceptor properties of the functional amino, imino, enol and keto groups vary considerably, being donor in one form and acceptor in the other. 

There are some additional possibilities for proton tautomerism with adenine, guanine, and cytosine (Fig. 15.5), where one of the protons can move from one ring nitrogen atom to another one. This type of tautomerism is restricted to the free bases and cannot occur in the nucleosides where pyrimidine N(l) and purine N(9) are substituted by the furanose moiety. 

The bases occur only in the canonical tautomeric forms [524, 525]. In both polar and nonpolar environments in the solid and solution states, the canonical forms of the bases illustrated in Fig. 15.1 are the only ones that have been observed. There is some spectroscopic NMR evidence for the occurrence of the nucleic acid bases in other tautomeric forms in solution, but only at or below the 0.01% level. This concentration is very difficult to measure, if at all possible [123, 526]. 

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]. 

3 7r-Bond Cooperativity Enhances Hydrogen-Bonding Forces 

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