Thinking Outside the Cage: A New Hypothesis That Accounts for Variable Yields of Radicals from the Reaction of CO with ONOO.

In biology, the reaction of ONOO with CO is the main sink for ONOO. This reaction yields CO, NO, NO, and CO. There is a long-standing debate with respect to the yield of the radicals relative to ONOO. The reaction of ONOO with CO results at first in ONOOCO. According to one hypothesis, ONOOCO is extremely short-lived and devolves into a solvent cage that contains CO and NO. Of these solvent cages, approximately two/thirds result in NO and CO, and approximately one/third release CO and NO that oxidize the substrate. According to our hypothesis, ONOOCO is formed much faster, is relatively long-lived, and may also be an oxidant; the limited yield is the result of ONOOCO being scavenged by a second CO under conditions of a high CO concentration. We disagree with the first hypothesis for three reasons: First, it is based on an estimated for the reaction of ONOO with CO to form ONOOCO of ∼1 M, while experiments yield a value of 4.5 × 10 M. Second, we argue that the solvent cage as proposed is physically not realistic. Given the less than diffusion-controlled rate constant of CO with NO, all radicals would escape from the solvent cage. Third, the reported ∼33% radical is not supported by an experiment where mass balance was established. We propose here a hybrid mechanism. After formation of ONOOCO, it undergoes homolysis to yield CO with NO, or, depending on [CO], it is scavenged by a second CO; CO oxidizes ONOO, if present. These reactions allow us to successfully simulate the reaction of ONOO with CO over a wide range of ONOO/CO ratios. At lower ratios, fewer radicals are formed, while at higher ratios, radical yields between 30% and 40% are predicted. The differences in radical yields reported may thus be traced to the experimental ONOO/CO ratios. Given a physiological [CO] of 1.3 mM, the yield of CO and NO is 19%, and lower if ONOOCO has a significant reactivity of its own.