The mechanism of DNA alkylation by the β-electrophilic center of nitrosamines and nitrosoureas: a theoretical study

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 optimized at the B3LYP/6-311+G(d,p) theoretical level. Intrinsic reaction coordinate (IRC) and molecular orbital analysis are calculated to investigate the reaction pathways, and the activation energy and the relative energy of the intermediates are calculated. Because the carbonyl group delocalize the π electrons in the molecular system, the negative charges on the nitroso oxygen atom of nitrosoureas are much lower than that of nitrosamines. The results show that nitrosamines are more favorable to undergo the anchimeric assistant process than nitrosoureas, which indicates that the alkylating activity of the beta-electrophilic center of nitrosamines is higher than that of nitrosoureas. It is supposed that the distinct anchimeric assistant activity of the nitroso group attribute to the difference of the carcinogenicity between nitrosamines and nitrosoureas.