Perceptions of peroxynitrite reactivity – Then and now

Many chemical and biological reactions involving peroxynitrite 3 occur by unusual rate laws that are independent of the identity of the reacting partner. The true nature of these reactions and the identities of actual reactive species have been the subject of considerable debate ever since the notion that peroxynitrite is an important component of oxidative stress was first introduced in the early 1990s. We present herein a succinct historical review of this topic written from the perspective that intermediary inorganic free radicals are the causative agents in these reactions. This viewpoint provides a complete self-consistent rationalization of all verified data from multiple laboratories, whereas other explanations have been unable to do so. Recognition of the radical nature of peroxynitrite decomposition has also allowed a reassessment of the quantitative mechanism of CO 2 -catalyzed peroxynitrite decomposition. Detailed analyses indicate that the constant for rate-limiting formation of the putative reactive carbon dioxide adduct ( ONOOCO 2 − ) 3 is actually ∼20% less than previously recognized and CO 2 turnover numbers for catalysis (that is, the number of reaction cycles that CO 2 undergoes before being removed as bicarbonate) are relatively large and dependent upon the [CO 2 ]/[ONOO − ] ratio in the reaction environment.