ortho-Boronic Acid Carbonyl Compounds and Their Applications in Chemical Biology.

Iminoboronates and diazaborines are related classes of compounds that feature an imine ortho to an arylboronic acid (iminoboronate) or a hydrazone that cyclizes with an ortho arylboronic 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.

Diazaborines oxidize slowly with H2O2 but rapidly with peroxynitrite in aqueous buffer.

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) and peroxynitrite (ONOO-) oxidize arylboronic acids to their corresponding phenols. When used in molecular imaging probes and in ROS-responsive molecules, however, simple arylboronic acids struggle to discriminate between H2O2 and ONOO- because of their fast rate of reaction with both ROS. Here, we show that diazaborines (DABs) react slowly with H2O2 but rapidly with peroxynitrite in an aqueous buffer. In addition to their slow reaction with H2O2, the immediate product of DAB oxidation with H2O2 and ONOO- can yield a kinetically trapped CN Z-isomer that slowly equilibrates with its E-isomer. Taken together, our work shows that diazaborines exhibit enhanced kinetic discrimination between H2O2 and ONOO- compared to arylboronic acids, opening up new opportunities for diazaborine-based tools in chemical biology.