Issue 22, 2021

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

Abstract

Dynamic bonds continually form and dissociate at equilibrium. Carbonyl compounds with proximal boronic acids, including 2-formylphenylboronic acid (2-FPBA), have been reported to form highly dynamic covalent hydrazone and oxime bonds in physiological conditions, but strategies to tune the dynamics have not yet been reported. Here, we characterize the dynamics of 2-FPBA-derived hydrazones and oximes 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.

Graphical abstract: Tuning the exchange dynamics of boronic acid hydrazones and oximes with pH and redox control

Supplementary files

Article information

Article type
Paper
Submitted
01 Feb 2021
Accepted
12 Mai 2021
First published
13 Mai 2021

Org. Biomol. Chem., 2021,19, 4986-4991

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

G. S. Han and D. W. Domaille, Org. Biomol. Chem., 2021, 19, 4986 DOI: 10.1039/D1OB00191D

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