Effects of Protonation and C5 Methylation on the Electrophilic Addition Reaction of Cytosine: A Computational Study

The mechanism for the effects of protonation and C5 methylation on the electrophilic addition reaction of Cyt has been explored by means of CBS-QB3 and CBS-QB3/PCM methods. In the gas phase, three paths, two protonated paths (N3 and O2 protonated paths B and C) as well as one neutral path (path A), were mainly discussed, and the calculated results indicate that the reaction of the HSO₃^– group with neutral Cyt is unlikely because of its high activation free energy, whereas O2-protonated path (path C) is the most likely to occur. In the aqueous phase, path B is the most feasible mechanism to account for the fact that the activation free energy of path B decreases compared with the corresponding path in the gas phase, whereas those of paths A and C increase. The main striking results are that the HSO₃^– group directly interacts with the C5C6 bond rather than the N3C4 bond and that the C5 methylation, compared with Cyt, by decreasing values of global electrophilicity index manifests that C5 methylation forms are less electrophilic power as well as by decreasing values of NPA charges on C5 site of the intermediates make the trend of addition reaction weaken, which is in agreement with the experimental observation that the rate of 5-MeCyt reaction is approximately 2 orders of magnitude slower than that of Cyt in the presence of bisulfite. Apart from cis and trans isomers, the rare third isomer where both the CH₃ and SO₃ occupy axial positions has been first found in the reactions of neutral and protonated 5-MeCyt with the HSO₃^– group. Furthermore, the transformation of the third isomer from the cis isomer can occur easily

Reactivity of 5-carboxycytosine toward addition and hydrogen abstraction by ·OH in acetonitrile: a computational study

<p>Two distinct mechanisms of -mediated 5-carboxylcytosine (5-caCyt) at the CBS-QB3 approach with polarizable continuum model in acetonitrile have firstly been explored, the addition reaction (paths R1 and R2), the H-atom abstraction reaction (paths R3-R6), respectively. It indicates that the addition of to the C5 = C6 double bond of 5-caCyt remains more favourable than the H-atom abstraction, whether in the gas or aqueous phase. Meanwhile, there is a little difference in the free energy barrier between acetonitrile and water, showing that the solvent has small impact on the reactivity of -mediated 5-caCyt.</p

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

<p>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.</p

Computational study of the decomposition mechanisms of ammonium dinitramide in the gas phase

<p>CBS-QB3 method has been employed to determine the geometries, the vibrational frequencies of the reactants, the products and the transition states involved in intramolecular hydrogen-transfer and decomposition reactions of the free gas-phase H₃N···HN(NO₂)₂ (ADN^*). The results show that the intramolecular hydrogen-transfer reaction of ADN^* is more feasible than that of HDN. ADN^* and its hydrogen-transfer isomers ADN^*-IIa,b,c decompose along four channels to form NH₃ + HONO + 2NO (P_I), ȮH + ṄO₃ + N₂ + NH₃ (P_II), ȮH + ṄO₂ + N₂O + NH₃ (P_III), and HNO₃ + N₂O + NH₃ (P_IV), respectively. It has been found that the dominant decomposition channels are P_I and P_III. The hydrogen-transfer reaction can reduce the barrier of elimination of NO₂ and forming N₂O reactions in ADN^* and HDN. The decomposition of ADN^*-IIc to form NO₂ and N₂O is more feasible than that of the gas-phase HDN. The rate constants (<i>k</i>) of rate-determining step of ADN^* show that <i>k</i>_PI and <i>k</i>_PIII are higher than <i>k</i>_PIV and <i>k</i>_PII. Compared with HDN-IIc → N₂O+ȮH+ṄO₂, <i>k</i>_PIII of ADN^*-IIc is significantly higher than that of <i>k</i>^HDN-IIc. These results reveal that NH₃ (as a chaperon) has a certain influence on the decomposition mechanisms and kinetics of ADN^*.</p