Theoretical studies of DNA base deamination. 2. Ab initio study DNA base diazonium ions and of their linear, unimolecular dediazoniation paths

Deamination of the DNA bases cytosine, adenine, and guanine can be achieved by way Of diazotization and the diazonium ion's of the DNA bases are consi dered to be the key intermediates. The DNA-base diazonium ions are thought to undergo nucleophilic substitution by water or other available nucleophil es. Cross-link formation is thought to: occur if the amino group of a neigh boring DNA base acts as the nucleophile. All mechanistic hypotheses invokin g DNA base diazonium ions are based on product analyses and deduction and a nalogy to the chemistry of aromatic primary amines while none of the DNA ba se diazonium ions has been observed or characterized directly. We report th e results of an ab initio study of the diazonium ions 1, 3, and 5, derived by diazotization of the DNA bases cytosine, adenine, and guanine, respectiv ely, and of their unimolecular dediazoniations to form the cations 2, 4, an d 6, respectively. The dediazoniation paths of two iminol tautomers of 1 an d 5 also were considered. The unimolecular dediazonation paths were explore d and none of these corresponds to a simple Morse-type single-minimum poten tial. Instead, double-minimum potential curves are found in most cases, tha t is, minima exist both for a classical diazonium ion Structure (a structur e): as well as for an electrostatically bound cation-dinitrogen complex Ob structure), and these minima are separated by a transition state structure (c structure). Depending on the DNA base, either minimum may be preferred a nd each minimum may or may not be bound with respect to the free fragments; The iminol tautomer HO-5 of the guaninediazonium ion was found to be more stable than the guaninediazonium ion 5. Moreover, it was found that the uni molecular dissociation of 5 is accompanied by a concomitant pyrimidine ring opening leading to 6b rather than the generally discussed cation 6a. This discovery leads to the proposition of a mechanism that is capable of accoun ting for all available experimental and theoretical data. The stabilities; of the DNA; base diazonium ions toward dediazoniation follow the order C-N- 2(+) (3.7 kcal/mol) < A-N-2(+)(9.0 kcal/mol) approximate to G-N-2(+) (<10 k cal/mol) much less than Ph-N-2(+) (26.6 kcal/mol), and mechanistic implicat ions are discussed.