Ab initio Studies on the Carcinogenic Mechanism of the Derivatives of 3,5-Dimethyl-Nitrosopiperazine

3,5-Dimethyl-nitrosopiperazine (DMNP) is a kind of cyclic nitrosamine which was recognized as environment carcinogens. The carcinogenic potency of DMNP was observed to be different when their N atom was substituted with different groups. This distinction in the metabolic activation of alpha- and gamma-position was reported to contribute to their distinct carcinogenicity. In this work, ab initio computations were carried out to study the carcinogenic mechanism of alpha- and gamma-positions of DMNP and its derivatives. The results showed that the increase of the gamma-position activity induced the decline of the carcinogenic potency. However, the influence of the alpha-position activity was ambivalent, the carcinogenic potency can be reduced either too high or too low activity on alpha-position. This study of the metabolic processes of the alpha- and gamma-positions provided a theoretical evidence for the carcinogenic mechanism of cyclic nitrosamines.