A Theoretical Study on the Critical Difference between the Mechanism of DNA Alkylation by Nitrosamines and Nitrosoureas

Ab initio calculations are carried out to study the anchimeric assistance of the nitroso group on the beta- carbon electrophilic center of nitramines and nitrosoureas. The molecular structures are all optimized at the RHF/6-311 G(d,p) theoretical level, and intrinsic reaction coordinate (IRC) and molecular orbital analysis are performed to investigate the reaction process. Because the C=O group delocalizes the pi electrons in the molecular system, the negative charges on the nitroso oxygen atom of nitrosoureas are much lower than that of nitrosamines. Consequently, nitrosamines are more favorable to undergo the anchimeric assistant process. The activation energy and the relative energy of the intermediates are calculated, and the results show that the alkylating activity of nitrosamines is obviously higher than that of nitrosoureas. This result indicates that the difference of the carcinogenicity between nitrosamines and nitrosoureas can be attributed to the distinguishing anchimeric assistant activity of the nitroso group on the beta-position carbon.