Tautomers of the N-centered radical generated by reaction of SO4˙− with N1-substituted cytosines in aqueous solution. Calculation of isotropic hyperfine coupling constants by a density functional method

Abstract

In the reaction of SO₄˙⁻ with 1-methylcytosine, 2′-deoxycytidine (and with cytidine in the presence of HPO₄²⁻) a very prominent radical is observed by EPR spectroscopy [a(N3), a(N4) 1.18, 1.16 mT; H. Niehaus and K. Hildenbrand, J. Chem. Soc., Perkin Trans. 2, 2000, 947], but its structure could not be assigned. In the present study, the isotropic hyperfine coupling constants (hfcs) of ten radicals that may be formed under such conditions were computed by a density functional method. Agreement between experimental and calculated couplings is achieved with the iminyl radical 4 [a(N3), a(N4) calculated 1.23, 1.17 mT]. This radical is formed upon deprotonation of the intermediate cytidyl radical cation 2 at the exocyclic amino group. The ensuing aminyl radical 3 then transforms into its tautomer 4 by migration of the proton from N4 to N3. This mechanism is supported by quantum-mechanical calculations of the energies of the radicals which show that the tautomerisation 3 → 4 is exothermic. The following alternative pathways have been discussed and the hfcs of the ensuing radicals have been calculated: (i) formation of OH-adduct radicals upon reaction of the cytidyl radical cation with water, (ii) disproportionation of the OH-adduct radicals and subsequent generation of oxyl radicals upon oxidation of a 5-hydroxycytosine derivative by peroxodisulfate, and (iii) recombination of the aminyl radicals and oxidation of the N–N-linked dimer with the formation of hydrazyl-type radicals. None of the calculated hfcs of the resulting radicals match the experimental values.