Collision induced dissociation of protonated N-nitrosodimethylamine by ion trap mass spectrometry: Ultimate carcinogens in gas phase

Abstract

Collision induced dissociation of protonated N-nitrosodimethylamine (NDMA) and isotopically labeled N-nitrosodimethyl-d6-amine (NDMA-d6) was investigated by sequential ion trap mass spectrometry to establish mechanisms of gas phase reactions leading to intriguing products of this potent carcinogen. The fragmentation of (NDMA + H +) occurs via two dissociation pathways. In the alkylation pathway, homolytic cleavage of the N–O bond of N-dimethyl, N′-hydroxydiazenium ion generates N-dimethyldiazenium distonic ion which reacts further by a CH 3 radical loss to form methanediazonium ion. Both methanediazonium ion and its precursor are involved in ion/molecule reactions. Methanediazonium ion showed to be capable of methylating water and methanol molecules in the gas phase of the ion trap and N-dimethyldiazenium distonic ion showed to abstract a hydrogen atom from a solvent molecule. In the denitrosation pathway, a tautomerization of N-dimethyl, N′-hydroxydiazenium ion to N-nitrosodimethylammonium intermediate ion results in radical cleavage of the N–N bond of the intermediate ion to form N-dimethylaminium radical cation which reacts further through α-cleavage to generate N-methylmethylenimmonium ion. Although the reactions of NDMA in the gas phase are different to those for enzymatic conversion of NDMA in biological systems, each activation method generates the same products. We will show that collision induced dissociation of N-nitrosodiethylamine (NDEA) and N-nitrosodipropylamine (NDPA) is also a feasible approach to gain information on formation, stability, and reactivity of alkylating agents originating from NDEA and NDPA. Investigating such biologically relevant, but highly reactive intermediates in the condensed phase is hampered by the short life-times of these transient species.