Deamination of the radical cation of the base moiety of 2'-deoxycytidine: a theoretical study.

Five pathways leading to the deamination of cytosine (to uracil) after formation of its deprotonated radical cation are investigated in the gas phase, at the UB3LYP/6-311G(d,p) level of theory, and in bulk aqueous solvent. The most favorable pathway involves hydrogen-atom transfer from a water molecule to the N3 nitrogen of the deprotonated radical cation, followed by addition of the resulting hydroxyl radical to the C4 carbon of the cytosine derivative. Following protonation of the amino group (N4), the C4--N4 bond is broken with elimination of the NH3+(. ) and formation of a protonated uracil. The rate-determining step of this mechanism is hydrogen-atom transfer from a water molecule to the cytosine derivative. The associated free energy barrier is 70.2 kJ mol(-1).