Humans are continually exposed to nitrates, especially through food and water. The health hazard associated with nitrate results chiefly from the bacterial conversion of ingested nitrate to nitrite. Nitrite can react with substances, such as amines, to form N-nitroso compounds, e.g. n-nitrosamines, most of which are carcinogens. Little is known about the conversion of nitrate to potential nitrosating agents, either nitrite or oxides of nitrogen. Certain iron(III) macrocyclic nitrate complexes have been found to react with amines to form N-nitrosamines with the nitrate ligand serving as the source of the nitrosating agent. This reaction takes place with the complex dissolved in a lipophilic solvent, even with a water layer present. The macrocyclic ligand may be a porphyrin of the heme type or a closely related ring system. The nitrate complexes are readily formed in one of two ways, both starting with the Mu-oxo or hydroxo iron(III) complex dissolved in the lipophilic medium. If nitric oxide is bubbled into the solution, followed by dioxygen, or if the solution is shaken with a dilute, aqueous nitric acid solution, the nitrate complex is produced rapidly. If the Mu-oxo or hydroxo iron(III) complex is dissolved in a lipophilic solvent and the solution shaken with a slightly acidic, nitrate solution containing amine, the amine undergoes nitrosation. Nitrate complexes appear to be intermediates in this catalytic formation of N-nitrosamines, using nitrate as the indirect nitrosating agent. This proposed study will investigate the nature of the iron(III) nitrate complexes - their mode of formation, their reactivity with amines, and their ability to serve as intermediates in the catalytic formation o the N-nitrosamines. Iron(III) macrocyclic complexes, a type of complex known to be present in many biomolecules, will be shown to serve as a promotor for the N-nitrosation of amines by nitrate. This study will also provide some needed information on the modes by which nitrate is reduced to potential nitrosating species.
