Structure–Reactivity Relationships in Boronic Acid–Diol Complexation

Abstract

Boronic acids have found widespread use in the field of biomaterials, primarily through their ability to bind with biologically relevant 1,2- and 1,3-diols, including saccharides and peptidoglycans, or with polyols to prepare hydrogels with dynamic covalent or responsive behavior. Despite a wide range of boronic acid architectures that have been previously considered, there is a need for greater understanding of the structure-reactivity relationships that govern binding affinity to diols. In this study, various boronic acids and other organoboron compounds were investigated to determine their p<i>K</i> _a and their binding constants with the biologically relevant diols including sorbitol, fructose, and glucose. Boronic acid p<i>K</i> _a values were determined through spectroscopic titration, whereas binding constants were determined by fluorescence spectroscopy during competitive binding studies. Key structure-reactivity relationships clearly indicated that both boronic acid structure and solution pH must be carefully considered. By considering a variety of boronic acids with systematically varied electronics and sterics, these results provide guidance during selection of organoboron compounds in sensing, delivery, and materials chemistry.