A comprehensive study on the impact of the substituent on pK_a of phenylboronic acid in aqueous and non-aqueous solutions: A computational approach

The acid dissociation constant (pK_a) is the fundamental physicochemical properties required to understand the structure and reactivity of boronic acid-based material as a sensor that identifies carbohydrates. However, there is a lack of comprehensive study on the impact of the substituent on the pK_a of monosubstituted phenylboronic acid in aqueous and non-aqueous solutions. In this work, extensive experimental data on the pK_a of monosubstituted phenylboronic acid in an aqueous solution was reviewed and compared in terms of accuracy. In addition, computational, were used to predict and investigate the impact of the substituent on the pK_a for a series of monosubstituted phenylboronic acid in an aqueous solution at the molecular level. Good agreement was observed between predicted and literature pK_a values of monosubstituted phenylboronic acid in the aqueous solution. While some deviations exist, predominantly with fluorine-containing phenylboronic acid, the COSMO-RS model is proficient at predicting the pK_a of boronic acid in an aqueous solution with the accuracy of ±1.5 pKa. Subsequently, the model was used to predict the pK_a of boronic acid in the non-aqueous solution, which data is not available in the literature. Furthermore, an excellent relationship is observed between the acidity of para-substituted, and to some extent, meta-substituted phenylboronic acid with the atomic charge of acidic hydrogen calculated using Natural Bond Orbital (NBO) Population Analysis. In contrast, the steric hindrance and the existence of other molecular forces might influence the acidity of ortho-substituted phenylboronic acid. The gathered information in this work could be of benefit for the understanding of the acidity of the boronic acid-based materials not only as a sensor but also in many diverse areas.