Cytosine canonical forms

Differences in the IR spectra of cytosine, cytidine, and cytidylic acid were considered by Angell.41 This author concluded that the cytidylic acids exist in the solid state in a zwitterion form with one of the hydrogen atoms from the phosphate group at N-3 of the cytosine ring (cf.refs.53,54). Previously Miles 44 postulated that the form 7a rather than the form 8 was the structure of cytidine in acid solution. This conclusion is essentially the same as that of Tsuboi et al.i7 who proposed form 7b for the protonated form of cytidine, as 7a and 7b are two canonical forms of the same tautomer (7). 

The experimental and theoretical investigations of the relative stability of the tautomers of the DNA bases reveal that several tautomers of guanine and cytosine have (in gas phase) the relative stability which is only slightly different (1-2 Kcal-mof ) from the stability of their canonic forms [61, 125]. Such studies qualitatively support the theory of spontaneous mutations in the DNA which considers the appearance of the rare DNA bases tautomers as the natural source of the mutations [130]. On the other hand, the surrounding of the DNA bases in the living cell is definitely different from the gas phase, so the investigations of the role of the polar environment on the stability of the different tautomers are extremely important. 

Figure 2 Canonical forms of cytosine, uracil, and thymine...

Nucleobases, such as cytosine, thymine, and uracil are the most important pyrimidine derivatives. In a recent gas-phase study [64], three low-energy tautomers were identified on the basis of CCSD(T)/cc-pVQZ energy calculations andMP2/6-311++G(2d,2p) estimation ofthe vibrational frequencies. The authors emphasize the importance of the high-level estimation of the frequencies and the related thermal correction in order to obtain rehable AG within a 0.7 kcal mol free energy range of the tautomers at T = 450 K. The lowest-free-energy structure is the canonical hydroxy-amine form of cytosine. 

Besides the canonical triplexes formed, for example, between thymine and the adenine-thymine base pair and cytosine and the guanine-cytosine base pair other combinations have been suggested to form stable triplexes, e.g. G-TA, G-GC and T-GC [43], The stability of triplexes depends on pH, ionic strength, temperature, and, in cases where the Watson-Crick duplex is part of a plasmid DNA, it depends on supercoil density [44]. 

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