Hydrazone and oxime are dynamic covalent bonds that continually form and dissociate at equilibrium. 2-formylphenylboronic acid (2-FPBA) forms especially dynamic covalent hydrazone and oxime bonds in physiological conditions. However, systematic strategies to tune the dynamics of the bond formation and dissociation have not yet been reported. Here, we characterize the dynamics of 2-FPBA-derived hydrazone and oxime and account for both the rapid rate of formation (~102-103 M-1 s-1) and the relatively fast rate of hydrolysis (~10-4 s-1) at physiological pH. We further show that these substrates undergo exchange with α-nucleophiles, which can be reversibly paused and restarted with pH control. Finally, we show that oxidation of the arylboronic acid effectively abolishes the rapid dynamics, which slows the forward reaction by more than 30,000 times and increases the hydrolytic half-life from 50 minutes to 6 months at physiological pH. These results set the stage to explore these linkages in dynamic combinatorial libraries, reversible bioconjugation, and self-healing materials.

Tuning the dynamics of boronic acid hydrazones and oximes with pH and redox control

ACS Spring Meeting 2021

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