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Article Proposes New Approach for Specific Detection of Peroxynitrite

An international collaboration among scientists in the Department of Biophysics at the ³ΙΘΛΏμΚΦ and Lodz University of Technology in Poland resulted in publication of the article, "Phenyl Radical-Mediated Fluorogenic Cyclization for Specific Detection of Peroxynitrite," in Analytical Chemistry. The abstract follows:

Peroxynitrite (ONOO–), a biological oxidizing and nitrating species responsible for post-translational modification of cellular proteins, has been implicated in numerous pathologies carrying an inflammatory component. Specific detection of ONOO– in biological systems remains a challenge, and boronates are regarded as the mostZielonka_Analy Chem_Graphical Abstract promising class of probes for the detection and quantitation of ONOO–. Oxidation of boronate probes by ONOO– results in the formation of minor ONOO–-specific products via a pathway involving a phenyl radical-type intermediate, in addition to the major phenolic product. Here, we report fluorogenic cyclization of the phenyl-type radical formed during oxidation of a boronate probe by ONOO–, with the production of a fluorescent product, and we propose a new approach for the specific detection of ONOO– based on this observation. We characterized the kinetics and stoichiometry of the reaction of benzophenone-2-boronic acid with ONOO– and identified 2-hydroxybenzophenone as the major product and fluorenone (FLN) and 2-nitrobenzophenone as the minor ONOO–-specific products. Hydrogen peroxide neither alone nor in the presence of myeloperoxidase and nitrite produces FLN or 2-nitrobenzophenone. FLN can be selectively detected using fluorescence spectroscopy, providing a chemical principle for the development of next-generation probes for ONOO–, with noninvasive, fluorescence-based detection of ONOO–-specific products. Fluorescence-based monitoring of FLN was successfully applied for the detection of ONOO– generated in situ from the decomposition of SIN-1, a thermal source of the superoxide radical anion and nitric oxide.

This publication is licensed under CC-BY 4.0. 

Authors of the article comprise Jacek Zielonka, PhD, DSc, assistant professor in the Department of Biophysics at the ³ΙΘΛΏμΚΦ, and Aleksandra Grzelakowska, PhD, and RadosΕ‚aw PodsiadΕ‚y, PhD, from Lodz University of Technology.

The research was supported by Lodz University of Technology under the programme “Excellence Initiative - Research University” (FU2N, grant no. W3/1P/2022) (AG), the Polish National Agency for Academic Exchange under the Bekker NAWA program (project no. BPN/BEK/2022/1/00219) (AG), and NIH grant R01 CA280746 (JZ).