KINETICS OF N-NITROSATION IN OXYGENATED NITRIC OXIDE SOLUTIONS AT PHYSIOLOGICAL PH - ROLE OF NITROUS ANHYDRIDE AND EFFECTS OF PHOSPHATE AND CHLORIDE

摘要

The kinetics of N-nitrosation in oxygenated nitric oxide (NO) solutions at physiological pH are important because of the cytotoxic, mutagenic, and carcinogenic effects of NO and its derivatives. N-nitrosation of morpholine in the presence of NO and O-2 at pH 7.4 was investigated using a novel reactor in which NO, nitrite (NO2-), and N-nitrosomorpholine (NMor) were continuously monitored. A nitrogen balance showed that NO2- and NMor were the principal nitrogen products derived from NO. Phosphate and chloride ions were shown to inhibit N-nitrosation of morpholine, whereas nitrate, nitrite, thiocyanate, and perchlorate had little or no effect. The effects of phosphate, in particular, were substantial: 0.05 M phosphate caused a 20-fold reduction in NMor formation. All data were consistent with N2O3 being the principal nitrosating agent at physiological pH. A scheme in which phosphate and chloride react with N2O3 to form nitrosyl compounds, which are then rapidly hydrolyzed to NO2-, explains the inhibitory effects of these anions, Rate constants for the reactions of morpholine, phosphate, and chloride with N2O3 were estimated at 25 and 37 degrees C. Relations were derived to predict the concentrations of N2O3 and the various nitrosyl complexes, based on pseudo-steady-state assumptions applied to these and other species present in small amounts. [References: 23]