Facilitated tobacco-specific nitrosamine formation from nicotine in the presence of Cu2+ ions

Regular practice in tobacco farming recognizes that copper is one of the essential micronutrients in tobacco (Nicotiana tabacum). We report here that copper is present in significant levels in post-harvested, cured tobacco. Transition metals have been shown to catalyze the formation of nitrosamines from amines of which nicotine, the most sought-after component in tobacco, is a tertiary amine. We found, using the nicotine-copper model system, Cu2+ facilitates nitrosamine formation. A mechanistically plausible route for this metal ion-mediated nitrosamine formation from alkaloids is the nicotine-Cu2+ complex formation where Cu2+ preferentially binds to the pyridine nitrogen of nicotine in a pH-dependent fashion. Knowing that tobacco also contains other alkaloids, e.g., anabasine and anatabine, Cu2+ could also enhance the production of nitrosamines from other tobacco-specific alkaloids.