2-formylphenylboronic acid (2-FPBA) forms oximes and hydrazones at an exceptionally rapid rate and undergo highly dynamic exchange with competing α-nucleophiles, owing to the formation of 5-membered heterocyclic intermediate structure. At the same time, certain hydrazones can form a 6-membered heterocyclic product, diazaborine (DAB), in physiological conditions that further stabilizes the addition product. We characterized the dynamics of such oximes and DABs by measuring the rates of formation and hydrolysis at physiological pH. We show that these substrates undergo exchange with α-nucleophiles, which can be reversibly paused and restarted with pH control or abolished upon arylboronic acid oxidation, and that DABs exhibit a unique exchange trend with hydrazides that differs from the oxime exchange trend. Finally, we show that DABs are oxidized with hydrogen peroxide (H2O2) at a significantly slower rate than arylboronic acids but are rapidly oxidized in the presence of peroxynitrite (ONOO-). Our findings suggest that DAB is a privileged class of peroxynitrite-reactive motifs for chemical biology applications.

Dynamic exchange and oxidation reactivity of boronic acid oximes, hydrazones, and diazaborines.

ACS Spring 2022

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