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Abstract We present the synthesis, properties, and imaging applications of a new class of diazaborine‐based probes (Peroxynitrite Probe‐1,PNP‐1) for selective peroxynitrite (ONOO⁻) imaging in live cells.PNP‐1features a diazaborine‐based reaction motif that provides excellent discrimination between H₂O₂and ONOO⁻, solving a persistent challenge of organoboron‐based fluorescent probes for oxidative metabolite imaging. We demonstrate the utility ofPNP‐1to detect endogenously produced ONOO⁻in live RAW 264.7 macrophages by fluorescence microscopy, with probe selectivity confirmed with inhibition of NADPH oxidases and nitric oxide synthase, the requisite enzymatic machinery for ONOO⁻production. Co‐localization studies unexpectedly reveal preferential mitochondrial localization, which we show is dependent on the naphthalimide scaffold. Taken together, our results show that diazaborines are a novel motif for selective ONOO⁻reactivity, positioning them for incorporation into other ONOO⁻‐specific chemical biology tools. 

Abstract Iminoboronates and diazaborines are related classes of compounds that feature an imineorthoto an arylboronic acid (iminoboronate) or a hydrazone that cyclizes with anorthoarylboronic acid (diazaborine). Rather than acting as independent chemical motifs, the arylboronic acid impacts the rate of imine/hydrazone formation, hydrolysis, and exchange with competing nucleophiles. Increasing evidence has shown that the imine/hydrazone functionality also impacts arylboronic acid reactivity toward diols and reactive oxygen and nitrogen species (ROS/RNS). Untangling the communication between C=N linked functionalities and arylboronic acids has revealed a powerful and tunable motif for bioconjugation chemistries and other applications in chemical biology. Here, we survey the applications of iminoboronates and diazaborines in these fields with an eye toward understanding their utility as a function of neighboring group effects.