Molecular Characterization and Formation of Novel Reversible Boronic Acid Complexations

Abstract

Boronic acids have an impact on various applications in drug discovery and medicinal chemistry. Therefore, an understanding of their structure and reactivity is essential. Determining the pKa of novel synthesized boronic acids was conducted to investigate the structural changes of the boron center. We estimated one pKa value for each compound and showed reversibility to a select boronic acid derivatives. Next, we demonstrated and quantified a series of binding experiments at physiological pH. The iminoboronate formation between Boc-Lysine and carbonyl boronic acid derivative was successfully quantified. We found that compound DT14 had the highest binding affinity across the carbonyl derivatives. Diazaborine formation between Boc-Lysine and aldehyde derivatives did not demonstrate significant binding. Finally, diol binding between common saccharides and boronic acids was successfully quantified. We found that glucuronic acid bound tight to carboxylic acid derivatives. UV-Visible, NMR and Fluorescence spectroscopy were used to quantify the physicochemical properties and binding interactions.