The relationship among pKa, pH, and binding constants in the interactions between boronic acids and diols—it is not as simple as it appears

In our continuing efforts into designing boronic acid-based sensors that recognize cell-surface carbohydrates, it has been necessary to examine various factors that affect the binding affinity between a boronic acid moiety and a diol. The current prevailing view is that the strongest boronic acid/diol complexes are generated by a combination of high solution pH and a low boronic acid pKa. However, there has never been a systematic examination of the relationship among the binding constants, boronic acid pKa, and the pH of the solution. Herein we report our findings with a series of 25 arylboronic acids with various substituents and their binding affinities with diols. We have found that (1) the relationship between the pKa of monosubstituted phenylboronic acid and its substituents can be described using a Hammet plot; (2) the optimal pH for binding is not always above the pKa of the boronic acid, and is affected by the pKa values of the boronic acid and the diol, and other unknown factors; and (3) the general belief that boronic acids with lower pKa values show greater binding affinities for diols is not always true.