Organic Chemistry

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

Dylan Domaille Colorado School of Mines

Abstract

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.

Content

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Supplementary material

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