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 pKa and their binding constants with the biologically relevant diols including sorbitol, fructose, and glucose. Boronic acid pKa 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.