Rapid formation of N-nitrosamines from nitrogen oxides under neutral and alkaline conditions.
The formation of carcinogenic N-nitrosamines in neutral and alkaline aqueous solutions (pH 6-14) at 25 degrees C is reported using dissolved N2O3 and N2O4 gases. These reactions are very much faster than those with acidified nitrite: typically, 2 X 10(-3) M amine gives ca. 10-50% N-nitrosamine in a few seconds with 5-20 fold excess of nitrogen oxide. The N-nitrosamine yield in 0.1 M sodium hydroxide is independent of amine basicity from pKA 11.2-0.99, but decreases with decreasing pH of the reaction solution for the more basic amines. Significantly, N-nitrosamine yields are not lowered with diluted nitrogen oxides (1000 ppm) and moderately basic amines (eg. N-methylpiperazine) react readily at physiological pH. The mechanism by which these reactions occur is discussed, with particular reference to the existence of two reactive tautomeric forms of N2O3 and N2O4. The formation of carcinogenic N-nitrosamines from NO in ethanol at 25 degrees C is also reported. These reactions are slow in the absence of air (oxygen), I2 or metal salts. Oxygen accelerates nitrosation by converting NO via NO2 to either N2O3 or N2O4, but both I2 and metal salts are effective under anaerobic conditions, where reaction rates are virtually independent of amine basicity but depend on the nature of the added reagent. The most effective substance is I2, which gives quantitative yields of N-nitrosamine in a few minutes at 25 degrees C by forming the reactive nitrosyl iodide (NOI) reagent. Acceleration in ethanol at 25 degrees C is also observed with AgI, CuI, CuII, ZnII, FeIII and CoII salts, among others, with substantial amounts of N-nitrosamine being produced in ca. 30-300 min. Metal iodides intervene by way of the NOI reagent, as for I2, but other salts require a mechanism involving reaction between a metal-amine complex and NO, itself. The results show that carcinogenic N-nitrosamines may form under a much wider range of experimental conditions than suspected hitherto. Their relevance to human exposure is discussed, with particular reference to urban pollution and the effect of dietary antioxidants.
D000588:Amines; D055598:Chemical Phenomena; D002621:Chemistry; D006863:Hydrogen-Ion Concentration; D008670:Metals; D009569:Nitric Oxide; D009589:Nitrogen Oxides; D009602:Nitrosamines / Q000138:chemical synthesis*; D010880:Piperidines; D013997:Time Factors
D000588:Amines; D008670:Metals; D009589:Nitrogen Oxides; D009602:Nitrosamines; D010880:Piperidines; D009569:Nitric Oxide