Thinking Outside the Cage: A New Hypothesis That Accounts for Variable Yields of Radicals from the Reaction of CO2 with ONOO.

In biology, the reaction of ONOO- with CO2 is the main sink for ONOO-. This reaction yields CO3•-, NO2•, NO3-, and CO2. There is a long-standing debate with respect to the yield of the radicals relative to ONOO-. The reaction of ONOO- with CO2 results at first in ONOOCO2-. According to one hypothesis, ONOOCO2- is extremely short-lived and devolves into a solvent cage that contains CO3•- and NO2•. Of these solvent cages, approximately two/thirds result in NO3- and CO2, and approximately one/third release CO3•- and NO2• that oxidize the substrate. According to our hypothesis, ONOOCO2- is formed much faster, is relatively long-lived, and may also be an oxidant; the limited yield is the result of ONOOCO2- being scavenged by a second CO2 under conditions of a high CO2 concentration. We disagree with the first hypothesis for three reasons: First, it is based on an estimated K for the reaction of ONOO- with CO2 to form ONOOCO2- of ∼1 M-1, while experiments yield a value of 4.5 × 103 M-1. Second, we argue that the solvent cage as proposed is physically not realistic. Given the less than diffusion-controlled rate constant of CO3•- with NO2•, 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 ONOOCO2-, it undergoes homolysis to yield CO3•- with NO2•, or, depending on [CO2], it is scavenged by a second CO2; CO3•- oxidizes ONOO-, if present. These reactions allow us to successfully simulate the reaction of ONOO- with CO2 over a wide range of ONOO-/CO2 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-/CO2 ratios. Given a physiological [CO2] of 1.3 mM, the yield of CO3•- and NO2• is 19%, and lower if ONOOCO2- has a significant reactivity of its own.