Tuning the Dynamics of Boronic Acid Hydrazones and Oximes with pH and Redox Control

The reaction between acyl hydrazide and methylhydroxylamine with 2-formylphenylboronic acid (2-FPBA) are measured in aqueous buffer at concentrations appropriate for bioconjuagtion (0.1 mM). The data are well-described by a reversible kinetic model that is second-order in the forward direction (10² – 10³ M^-1 s^-1) and first-order in hydrolysis (~10^-4 s^-1). We further show the resulting diazaborines (DAB) and oximes undergo exchange with competing nucleophiles, and the rate of exchange can be tuned with pH control. Finally, we demonstrate that treatment with H₂O₂ converts the proximal boronic acid catalyst to a phenol, which abolishes the rapid dynamics, and increases the hydrolytic half-life of the resulting oxime from 50 minutes to 6 months.