INVOLVEMENT OF FREE NITRENIUM IONS, ION-PAIRS, AND PREASSOCIATION TRAPPING IN THE REACTIONS OF ESTER DERIVATIVES OF N-ARYLHYDROXYLAMINES AND N-ARYLHYDROXAMIC ACIDS IN AQUEOUS-SOLUTION

Rate and product yield data for the decomposition of the ester derivat ives of N-arylhydroxylamines and N-arylhydroxamic acids 1a-i in aqueou s solution in the presence of N-3(-) support a mechanistic scheme (Sch eme 5) in which the trapping by N-3(-) changes from trapping of the fr ee ion, to trapping of an ion pair, to a preassociation process as the ion becomes more reactive. When the rate constant for trapping of the free ion by solvent, k(s), < similar to 10(8) s(-1), trapping by both N-3(-) and solvent occurs almost exclusively at the free ion. When 10 (8) s(-1) < similar to k(s) < similar to 10(10) s(-1), a change in the mechanism occurs, and trapping of the ion pair by both solvent and N- 3(-) becomes important. In this range of reactivity there is also evid ence, based on the apparent magnitude of k(az)', the rate constant for N-3(-) trapping of the ion pair, that some of the reaction with N-3(- ) occurs though a preassociation process. When k(s) > similar to 10(10 ) s(-1) essentially all of the observed N-3(-) trapping occurs by a pr eassociation process because N-3(-), which cannot react with the ion p air faster than the diffusion limit, can no longer compete with solven t for the ion pair. This progression in trapping mechanisms as the ion becomes more reactive with solvent is apparently an important factor in determining the carcinogenic potential of aromatic amines and amide s which are metabolized into sulfuric and carboxylic acid esters of N- arylhydroxylamines and N-arylhydroxamic acids. Nitrenium ions that und ergo slow reactions with solvent are selectively trapped by biological ly relevant nucleophiles such as 2'-deoxyguanosine, As the rate consta nt for reaction with solvent increases, the nitrenium ion is no longer capable of undergoing selective trapping by nonsolvent nucleophiles b ecause these reactions are rate limited by diffusion, but solvent trap ping is not.