Benzoboroxoles as Efficient Glycopyranoside-Binding Agents in Physiological Conditions: Structure and Selectivity of Complex Formation

In contrast to normal boronic acids, o-hydroxymethyl phenylboronic acid (benzoboroxole) has the capability of complexing glycopyranosides efficiently in neutral water. The measurement of association constants with a panel of model hexopyranosides indicates that the preferred mode of binding is through a cis-3,4-diol, such as that found in galactopyranosides, and mass spectrometric studies support a 1:1 binding stoichiometry. The complexation of glucopyranosides is weaker, and they are bound through their 4,6-diol unit. Although several factors may explain the exceptional carbohydrate-binding behavior of this class of hemiboronic acids, the relatively high Lewis acidity of benzoboroxoles is a likely contributing factor along with subtle factors such as intramolecular hydrogen bonds with other hydroxyl groups in the resulting anionic complex. These results with hexopyranosides suggest that biologically relevant cell-surface oligosaccharides could be targeted in water using oligomeric benzoboroxole receptors.