Ab initio Researches on the Mechanism of DNA Alkylation by Nitrosamines

Ab initio computations are carried out to study the activity of alpha-and beta-positions metabolites of nitrosamines. Full geometric structure optimization has been done for all reactants, intermediates and transition states. The activation energies, vibrational frequencies and intrinsic reaction coordinate calculation are also performed. The results show that the activity of beta-position is higher than alpha-position. For simulating the reaction in cellular environment, a series of computations are performed in water at the same level. The results reveal that the activity of beta-position is enhanced stronger than alpha-position by solvent effect. It can be deduced that beta-electrophilic center may be the first one which alkylates on one of the DNA strands and then alpha-electrophilic center may alkylate on the other. These can explain the alkylation process of nitrosamines that would induce the crosslinks between the DNA complementary base pairs and initiate cancer finally.