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

Abstract

<div>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 (10<sup>2 </sup>– 10<sup>3</sup> M<sup>-1 </sup>s<sup>-1</sup>) and first-order in hydrolysis (~10<sup>-4</sup> s<sup>-1</sup>). 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 H<sub>2</sub>O<sub>2</sub> 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.</div><div><br></div>