Theoretical study of N-nitrosamines and their presumed proximate carcinogens.
Quantum mechanical calculations in the MINDO/3 and CNDO/2 approximations have been used to study possible mechanisms of action of the carcinogenic N-nitrosamines. Calculated reaction path profiles show that hydroxylation at either the C-H bonds or the amino nitrogen of the nitrosamine may result in the formation of an alpha-hydroxynitrosamine with some interesting structural and stereochemical constraints. Dissociation of the alpha-hydroxynitrosamine, along a concerted pathway or two-step mechanism, releases the alkyldiazohydroxide which subsequently decomposes to the alkylating agents responsible for cancer induction. On the basis of the results obtained for the decomposition of the alkyldiazohydroxide, the alkylation mechanism of N-nitrosamines does not appear to involve carbocation intermediates or diazomethane. The most likely alternative for the alkylation reaction is, then, direct nucleophilic attack (SN2) on the alkyldiazonium ion by basic sites on the DNA molecule.
D000478:Alkylation; D055598:Chemical Phenomena; D002621:Chemistry; D008956:Models, Chemical; D009602:Nitrosamines; D011789:Quantum Theory; D013816:Thermodynamics
D009602:Nitrosamines