AbInitio SCF MO calculations on the reaction of hydroxyl radical with cytosine

Abstract

. 64,914 (1986).Ab initio calculations have been carried out on the relative stabilities of various possible products of the reaction between cytosine and the OH radical. These products are of importance in modelling radiation damage to living tissues. The preferred theoretical gas-phase addition site is the C6 ring atom according to these calculations. The analysis of a series of possible contributions to solvent effects strongly suggests the predominance of intermolecular H bonds in stabilizing the experimentally observed C5 adduct.BEVERLEY G. EAToCK, WILLIAM L. WALTZ, et PAUL G. MEZEY. Can. J. Chem. 64,914 (1986).On a effectut de calculs ab initio sur les stabilitks relatives de divers produits possibles pour la rkaction de la cytosine avec le radical OH. Ces produits sont importants dans l'klaboration d'un modkle pour les dommages dfis B la radiation dans les tissus vivants. D'apr2s ces calculs thtoriques, le site prkftrt pour l'addition en phase gazeuse est l'atome de carbone C6. L'analyse d'une skrie de contributions possibles aux effets de solvant sugg2re fortement la prkdominance de liaisons hydrogknes intermoltculaires dans la stabilisation de l'adduit en C5 qui est observk expkrimentalement.[Traduit par la revue] Introduction Radiation damage to nitrogen heterocycles has attracted interest due to the relevance of such effects for biologically important systems. As an extension of studies on the reactions of OH radicals with N heterocyclic systems (pyridine, imidazole) (1, 2), we have investigated the attack of OH on the pyrimidine base cytosine. Experimental results on the reaction of OH with cytosine agree that ring addition occurs (3,4), but information on site preference for addition is obtained only by indirect methods (esr, pulse radiolysis) leaving results open to some controversy. Ab initio calculations, however, provide a direct aid to identification of favored product isomers, and have been shown to be useful in past studies, supplementing experimental results (1,2,5,6).Radiation damage to cytosine is of interest because of its status as a component of DNA. Consideration of the N bases of DNA as subjects for ab initio studies favors the pyrimidines, both because of their greater susceptibility to OH attack (7) and the simpler problem that the electronic structure of the pyrimidines represents, as compared to the purine bases. Although more information exists regarding reactions of OH with thymine and uracil, the greater experimental controversy for site preference of OH addition to cytosine lent impetus to the choice of cytosine as a subject for these calculations. A recent paper (8) suggested that site selection of OH attack of cytosine is more discriminating than for the analogous reactions with thymine and uracil and that the major product, in opposition to expectations from the results of our previous studies on OH reactions with N heterocycles (1,2), was the species favored on account of electrophilic interactions rather than being the most electronically delocalized product. These factor...

Fragmentation mechanisms of cytosine, adenine and guanine ionized bases

“…and C6 (0.421 a.u.). Because the HOMO is localized on the C5-C6 bond, the positive charge of C6 agrees with the hydration reaction of the cytosine cation radical leading to the attack of OH À on the C6 atom as studied by Wagner et al 53 One can also notice that ab initio calculations 54 reaction of OH with the cytosine leads to a preferential addition of OH onto the C6 atom, whereas experimental results 53 in aqueous solution indicate a preferential formation of the C5-OH product. The fragmentation of cytosine has been experimentally studied by mass spectroscopy in the gas phase by photoionization, 7,8 electron impact 13,17,18 and proton impact.…”