The keto–amino/enol tautomerism of cytosine in aqueous solution. A theoretical study using combined discrete/self-consistent reaction field models Original Research Article

The tautomeric equilibrium between the keto–amino and enol forms of cytosine was investigated in aqueous solution. Calculations in solution were performed using both combined discrete/self-consistent reaction field (SCRF) and SCRF methods. Complexes containing a cluster of seven water molecules filling up the first solvation shell of cytosine were used for combined discrete/SCRF calculations. Results indicate that SCRF methods overestimate the stability of the enol tautomers by about 10 kcal/mol. Thus, the free energies of tautomerization of the enol forms determined from combined discrete/SCRF methods are about 16–19 kcal/mol, whereas the estimates derived from the SCRF methods are about 6–8 kcal/mol.