The tautomeric exchange of nucleic acid bases

Abstract

For a series of PMR studies of cytidine and related compounds in D_2O solution at various pD, it was observed that the H_5 resonances of cytosine base are broad in some of these compounds at pD 4-7, while those of H_6 are not. We proposed that there is chemical exchange between two tautomeric forms of cytosine base to give rise to broadening of spectra. This chemical exchange was found to be catalyzed by both solvent (D_2O)and hydroxyl (OD^-) ion present in solution. The observation of sharp resonances in certain cytidine derivatives having only one possible tautomeric structure supports this proposal. Temperature study of H_5 resonances at different pD was used to investigate the kinetics of this exchange reaction. The percentage of its minor tautomer was estimated as 10 ± 2% in neutral aqueous solution and its life time is about 10^(-3) sec at room temperature. The activation energy of this tautomeric exchange is 7.5 ± 0. 5 kcal/mole. for D_2O catalysis and 2.5 ± 0.5 kcal/mole for OD^- catalysis. The relation between tautomeric exchange of nucleic acids and genetic mutation is also discussed.