Characterization of alkyldinitrogen species implicated in the carcinogenic, mutagenic and anticancer activities of N-nitroso compounds.
The syntheses of certain specifically 15N-labelled E and Z alkyldiazotates and alkylnitrosoamines, together with related dinitrogen species, including diazoalkanes, are reported. A study of their conformational and configurational equilibria by 15N and 13C nuclear magnetic resonance spectrometry has revealed: (1) corresponding pairs of E and Z alkyldiazotates do not interconvert at ambient temperatures in aprotic solvents; (2) a preferential Z conformer of the alkylnitrosamines; (3) a fast interchange of metal counterion between oxygen and nitrogen in the Z-diazotates, but a slow interchange of metal ion between oxygen and nitrogen in the corresponding E diazotates; (4) interconversion of Z aryldiazotates, via detectable Z and E diazohydroxides, to the E diazotates; and (5) rapid stereoelectronically-assisted decomposition of Z-alkyldiazotates to diazoalkanes, in contrast with the behaviour of the more stable E diazotates. Self-Consistent Field calculations ab initio show that Z methyl diazohydroxide is the higher energy and more reactive form, while the carbon is relatively soft. In contrast, the E isomer is the more stable (by congruent to 18.0 kcal/mol) and the carbon harder. These data are in accord with the view that the Z form (from N-nitrosodimethylamine) attacks G-O6 (softer center) preferentially by SN1, while the E form prefers to react at the harder G-N7 and by an SN2 mechanism. These data provide a rationale for the known propylation of G-N7 without rearrangement, for propylation of G-O6 with rearrangement and possibly for the origin of the characteristic G-O6 alkylation carcinogenic lesion.
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001391:Azo Compounds / Q000138:chemical synthesis*; D002273:Carcinogens / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D009153:Mutagens / Q000138:chemical synthesis*; D009603:Nitroso Compounds / Q000138:chemical synthesis*
D000970:Antineoplastic Agents; D001391:Azo Compounds; D002273:Carcinogens; D009153:Mutagens; D009603:Nitroso Compounds