Quantum chemical studies of alkyldinitrogen species implicated in nitrosamine carcinogenesis

• Published in: Canadian journal of chemistry Vol. 67; no. 4; pp. 625 - 633
• Main Authors: Demeunynck, Martine, Lown, J. William, Sapse, Anne-Marie
• Format: Journal Article
• Language: English
• Published: Ottawa, Canada NRC Research Press 01.04.1989; National Research Council of Canada
• Subjects: Biological and medical sciences; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Fundamental and applied biological sciences. Psychology; Molecular and cellular biology; Carcinogenesis; Nitrosamine
• ISSN: 0008-4042; 1480-3291
• DOI: 10.1139/v89-094

Abinitio calculations (Hartree-Fock) at the level of 3-21G and 6-31G* as well as MP2/6-31G* have been performed on the carcinogen dimethylnitrosamine and its products of oxidative metabolism E- (and Z-) hydroxymethylmethylnitrosamines and certain ester conjugates. The E- and Z-hydroxymethylmethylnitrosamines are found to be close in energy and to be configurationally stable as is found experimentally. Alternative pathways are examined for the spontaneous decomposition of the primary metabolite in aqueous solution. Direct cleavage of E-hydroxymethylmethylnitrosamine to Z-methanediazohydroxide and formaldehyde is highly endothermic. Protonation of the NO group of the hydroxylated metabolite strongly stabilizes this species in contrast to nitrosoureas but in accord with experiment. Incorporation of water together with consideration of entropy effects satisfactorily accounts for the spontaneous exothermic decomposition of E-hydroxymethylmethylnitrosamine in aqueous media, as well as its relative stability in aprotic media. Abinitio calculations were also performed on selected nitrosoiminium ions which participate in the enzymatic activation and metabolism of certain dialkylnitrosamine carcinogens. Keywords: carcinogenesis, dimethylnitrosamine, abinitio calculations, nitrosoiminium ions.