Carbon dioxide-catalyzed peroxynitrite reactivity - The resilience of the radical mechanism after two decades of research

Author(s)

Augusto, Ohara ^[1] ; Goldstein, Sara ^[2] ; Hurst, James K. ^[3] ; Lind, Johan ^[4] ; Lymar, V, Sergei ; Merenyi, Gabor ^[4] ; Radi, Rafael ^{[5, 6]}

Affiliation

^[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-5508000 Sao Paulo - Brazil

^[2] Hebrew Univ Jerusalem, Chem Inst, IL-91904 Jerusalem - Israel

^[3] Oregon State Univ, Dept Biochem & Biophys, Corvallis, OR 97331 - USA

^[4] Royal Inst Technol, Sch Chem, S-10044 Stockholm - Sweden

^[5] Univ Republica, Ctr Free Rad & Biomed Res, Fac Med, Montevideo 11800 - Uruguay

^[6] Univ Republica, Dept Bioquim, Fac Med, Montevideo 11800 - Uruguay

• Document type: Review article
• Source: Free Radical Biology and Medicine; v. 135, p. 210-215, MAY 1 2019.
• Web of Science Citations: 5

Abstract

Peroxynitrite, ONOO-, formed in tissues that are simultaneously generating NO center dot and O-2(center dot-), is widely regarded as a major contributor to oxidative stress. Many of the reactions involved are catalyzed by CO2 via formation of an unstable adduct, ONOOC(O)O-, that undergoes O-O bond homolysis to produce NO2 center dot and CO3 center dot- radicals, whose yields are equal at about 0.33 with respect to the ONOO- reactant. Since its inception two decades ago, this radical-based mechanism has been frequently but unsuccessfully challenged. The most recent among these {[}Serrano-Luginbuehl et al. Chem. Res. Toxicol. 31: 721-730; 2018] claims that ONOOC(O)O- is stable, predicts a yield of NO2 center dot/CO3 center dot- of less than 0.01 under physiological conditions and, contrary to widely accepted viewpoints, suggests that radical generation is inconsequential to peroxynitrite-induced oxidative damage. Here we review the experimental and theoretical evidence that support the radical model and show this recently proposed alternative mechanism to be incorrect. (AU)

• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC