Aromatization of 9,10-Dihydroacridine Derivatives: Discovering a Highly Selective and Rapid-Responding Fluorescent Probe for Peroxynitrite

Abstract

As part of an effort to develop generally applicable strategies for creating probes suitable for detecting important molecular and ionic species, the oxidative aromatization of nonfluorescent 9,10-dihydroacridine derivatives triggered by peroxynitrite (ONOO^-) led to the identification of compound 2H, 9-phenyl-9,10-dihydroacridine-4-carboxylic acid, as a rapid-responding fluorescent probe capable of detecting ONOO^- with an extraordinary selectivity. Adding a little more than 1 equiv of ONOO^- to a solution of 2H resulted in over 100-fold fluorescence enhancement. In sharp contrast, treating 2H with excessive amounts of other oxidants that often interfere with the detection of ONOO^- failed to lead to noticeable fluorescence increase. The reaction of ONOO^- with 2H shows a similar efficiency in the pH range of 2-8. Low cytotoxicity was observed for 2H and its aromatized product. Bioimaging experiments revealed the promising potential of 2H as a new fluorescent probe for the selective detection of intracellular ONOO^-.