Effects of C5-substituent group on the hydrogen peroxide-mediated tautomerisation of protonated cytosine: a theoretical perspective

The direct tautomerism (path A) and H₂O₂ as a catalyst (path B) have been studied in conversion of Cyt2t⁺ into CytN3⁺ isomer. The protonated 5-carboxycytosine (5-caCyt) is represented and has been further explored in the presence of H₂O₂ (path C). In going from a four-membered-ring transition state in the case of the direct tautomerism to the six-membered ring for H₂O₂, the H₂O₂ significantly contributes to decreasing the free energy barrier of tautomerisation. Although the carboxylic substituent of 5-carboxycytosine has certain affected on the electron distribution of the pyrimidine ring, the six-membered-ring transition state has not changed. This result illustrates that the C5-carboxylation has no significant effect on the H₂O₂-mediated isomerisation of Cyt2t⁺ to CytN3⁺ isomer. Meanwhile, these paths A–C have been further explored in the presence of two water molecules. Use of implicit solvent models (PCM) does not significantly alter the energetics of water-mediated paths A–C compared to those in gas phase. Furthermore, the rate constant with Wigner tunnelling correction of path A is obviously smaller than those of paths B and C. Finally, the lifetime τ_99.9% of paths B and C is 10⁻⁵ s, which is implemented by the mechanism of the concerted synchronous double proton transfer.