Cytosine cations, tautomerism

The 77-SCF MO method and the Del Re procedure for u-electrons have been applied by Danilov148 to evaluate the enthalpy changes on tautomeric conversion 2 -> 6 in the ground state and the first excited singlet state for cytosine and its anionic and cationic forms. The results show that although in the ground state of cytosine the tautomeric... 

In general, the problem of tautomerism in nucleic acid bases has been approached by comparing the IR spectra of several isoelectronic model compounds. The model corresponding to the cytosine tautomers 4 or 5 have not yet been investigated. The IR spectroscopy studies cannot therefore definitely rule out these tautomers. It seems, however, that they do rule out form 6 for cytosine and cytidine and indicate that the dominant tautomer of the compounds in aqueous solution is the lactam-amino form 2, and that the protonated cations have the structure 7. 

The first PMR spectra57,58 attributed the tautomeric structure (7) to the cation of cytosine, in agreement with X-ray studies and IR data. For the preferred neutral form of cytosine in solution Kokko et al.59... 

UV and NMR studies showed that l-methyl-A -hydroxycytosine and its methyl derivatives exist predominantly in the oxo-imino form (up to 90%) (98BPC87). A review of the structure and properties of isolated nucleic acid bases with the special attention given to metal-cation-assisted tautomerization and the solvent effects has been published (99CR3247). Tautomerism of protonated cytosine has been studied experimentally by IR and Raman spectra and theoretically by ab initio and DFT calculations (96JPC5578). Neutral and protonated forms of cytidine monophosphate have been studied by ultraviolet resonance Raman spectroscopy. The amino oxo tautomer was found to be the most stable, followed by the imino oxo form. The imino-hydroxy tautomer was determined to be the least stable one. Upon protonation, the amino-oxo structure is retained (93JA760). 

There are seven possible tautomeric forms for cytosine (XLIX, Lllla-f). That the actual predominant tautomeric structure is (XLIX) has been adequately shown from ultraviolet spectral comparisons with N- and 0-methyl derivatives in aqueous solution [214-216], from proton magnetic resonance studies in dimethyl sulphoxide and other solvents [214, 217], from infrared spectra in the solid state [218], and from X-ray crystallography [219]. Cytosine has pX values of 4-45 and 12-2 for the dissociation of the cation and base, respectively [215] therefore, in neutral medium, the molecule is uncharged. The corresponding 1- and 3-methylcytosines have pK values of 4-55 [215] and 7-49 [214] respectively for the dissociation of the cations, from which the equilibrium constant for the tautomeric forms (XLIX) and (Lllla) of cytosine may be calculated as c. 10 in favour of (XLIX) [214] pro tonation of cytosine occurs at N3 [214],... 

An important effort is being presently done to study, both experimentally and theoretically, the excited states of compounds that exist in several tautomeric forms for instance, the singlet and triplet excited-state dynamics of the keto and enol tautomers of cytosine [27], the ultrafast excited-state decay of allopurinol keto-N9H tautomer from gas phase to aqueous solution [28], the reduced aromaticity in lysine-tryptophan dipeptide (lys-trp) cations, and the fact that the high pH tautomer correlates with lower quantum yield and shorter hfetimes [29]. The structure of the compounds appear in bold to call the attention to their biological and pharmaceutical nature. 

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