Detailed Mechanism of the Reaction of Phenylboronic Acid Derivatives with D-Fructose in Aqueous Solution: A Comprehensive Kinetic Study

A detailed kinetic study of the reactions of phenylboronic acid (PhB(OH)₂), 2-methylphenylboronic acid (2-MePhB(OH)₂), 2-isopropylphenylboronic acid (2-ⁱPrPhB(OH)₂), and 1-hydroxy-3H-2,1-benzoxaborole (BxB(OH)) with D-fructose was carried out to clarify the nature of the reactive boron species in D-fructose sensing and investigate the corresponding reaction mechanism. Both the boronic acids (RB(OH)₂) and boronate ions (RB(OH)₃ ⁻) were reactive toward D-fructose, while out of the five D-fructose anomers only α-D-fructofuranose was reactive toward boron species. The reactions of all substrates proceeded consecutively in two steps (steps 1 and 2). We concluded that the first intermolecular step (step 1) corresponds to the parallel reactions (two parallel reactions for 2-ⁱPrPhB(OH)₂ and three for the other systems) of the boronic acid and the boronate ion with α-D-fructofuranose to form bicoordinate complexes (mixture of exo- and endo-isomers), and the second intramolecular step (step 2) corresponds to the formation of a tricoordinate α-D-fructofuranose complex from the bicoordinate complexes. It was found that both the boronic acid and the boronate ion were kinetically reactive toward D-fructose, with the latter being more reactive.