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

Abstract

In biology, the reaction of ONOO − with CO 2 is the main sink for ONOO − . This reaction yields CO 3•− , NO 2 • , NO 3 − , and CO 2 . There is a long-standing debate with respect to the yield of the radicals relative to ONOO − . The reaction of ONOO − with CO 2 results at first in ONOOCO 2− . According to one hypothesis, ONOOCO 2 − is extremely short-lived and devolves into a solvent cage that contains CO 3•− and NO 2 • . Of these solvent cages, approximately two/thirds result in NO 3 − and CO 2 , and approximately one/third release CO 3and NO 2• that oxidize the substrate. According to our hypothesis, ONOOCO 2 − is formed much faster, is relatively long-lived, and may also be an oxidant; the limited yield is the result of ONOOCO 2− being scavenged by a second CO 2 under conditions of a high CO 2 concentration. We disagree with the first hypothesis for three reasons: First, it is based on an estimated K for the reaction of ONOO − with CO 2 to form ONOOCO 2 − of ∼1 M −1 , while experiments yield a value of 4.5 × 10 3 M −1 . Second, we argue that the solvent cage as proposed is physically not realistic. Given the less than diffusion-controlled rate constant of CO 3•− with NO 2• , 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 2 − , it undergoes homolysis to yield CO 3 •− with NO 2• , or, depending on [CO 2 ], it is scavenged by a second CO 2 ; CO 3 •− oxidizes ONOO − , if present. These reactions allow us to successfully simulate the reaction of ONOO − with CO 2 over a wide range of ONOO − /CO 2 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 2 ratios. Given a physiological [CO 2 ] of 1.3 mM, the yield of CO 3•− and NO 2• is 19%, and lower if ONOOCO 2 − has a significant reactivity of its own.

Solvent Cage Concept for the Homolytic Fragmentation of the Peroxynitrite-CO2 Adduct, ONOOCO2–

“…In accord with a previous study that two conformers of ONOO – can be respected, two isomers of ONOOCO 2 – were predicted to exist in aqueous solution (Figure and Table ), s-cis-gauche structure 1c and a slightly less stable s-trans-gauche one, structure 1t (Δ R G aq = 2.5 kcal mol –1 ; Table , entry 7). This contradicts Koppenol et al., who represented ONOOCO 2 – always as a planar s-trans structure, thereby also neglecting structure-related reactivities. (It should be noted that gauche arrangements are the common conformations of peroxides; planar s-trans geometries of peroxides are found only for bulky substituents, as, e.g., in t -BuOO t -Bu.…”

“…In any case, compounds 1c and 1t would be excellent precursors for CO 3 •– and • NO 2 radicals (eq ). A planar s-trans-trans structure, as presented by Koppenol et al, was found to be a high-lying [Δ H ⧧ aq = 27.2 kcal mol –1 (113.8 kJ mol –1 )] rotational transition state in the gas phase and found to be nonexistent in aqueous solution.…”

Engineering a Smart Nanofluidic Sensor for High-Performance Peroxynitrite Sensing through a Spirocyclic Ring Open/Close Reaction Strategy

“…Recently, Koppenol et al have reported the reaction between CO 2 with ONOO − . 61 Therefore, in this work, we degassed all of the solutions to minimize the solubility of carbon dioxide to prevent carbon dioxide from causing great interference to ONOO − detection. As depicted in Figures 4a−c and S5, S6, the reversal rectifying characteristics, gating ratio, and wetting behavior of the nanosensor toward ONOO − were significantly higher than toward other analytes.…”

“…Next, the selectivity of this nanosensor toward ONOO – was thoroughly assessed by investigating a range of analytes, including CO 2 , CO, H 2 S, H 2 O 2 , HSO 3 – , NH 4 + , and • OH, especially CO 2 , the main sink for ONOO – detection. Recently, Koppenol et al have reported the reaction between CO 2 with ONOO – . Therefore, in this work, we degassed all of the solutions to minimize the solubility of carbon dioxide to prevent carbon dioxide from causing great interference to ONOO – detection.…”

On the irrelevancy of hydroxyl radical to DNA damage from oxidative stress and implications for epigenetics

“…Endogenous oxidative damage to DNA should be mainly attributed to carbonate radical anion, the product of both the Fenton reaction in the intracellular medium and the decomposition of peroxynitrite in the presence of CO 2 . [1][2][3][5][6][7] Hydroxyl radical chemistry with DNA may still be important in radiation damage during tumor treatment with ionizing radiation or from environmental exposure to x-rays or intense UV light. 4 In addition, formation of ROS in highly localized concentrations may permit HO • to exact its nonspecific damage on DNA when oxidative stress is rampant.…”