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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. 

Reactive oxygen and nitrogen species are small reactive molecules derived from elements in the air─oxygen and nitrogen. They are produced in biological systems to mediate fundamental aspects of cellular signaling but must be very tightly balanced to prevent indiscriminate damage to biological molecules. Small molecule probes can transmute the specific nature of each reactive oxygen and nitrogen species into an observable luminescent signal (or even an acoustic wave) to offer sensitive and selective imaging in living cells and whole animals. This review focuses specifically on small molecule probes for superoxide, hydrogen peroxide, hypochlorite, nitric oxide, and peroxynitrite that provide a luminescent or photoacoustic signal. Important background information on general photophysical phenomena, common probe designs, mechanisms, and imaging modalities will be provided, and then, probes for each analyte will be thoroughly evaluated. A discussion of the successes of the field will be presented, followed by recommendations for improvement and a future outlook of emerging trends. Our objectives are to provide an informative, useful, and thorough field guide to small molecule probes for reactive oxygen and nitrogen species as well as important context to compare the ecosystem of chemistries and molecular scaffolds that has manifested within the field.