Theoretical coupling and stability of boronic acid adducts with catecholamines

Background: Catecholamines combined with boric/boronic acids are attractive chemical agents in drug design because some of their adducts have shown interesting biological activity. Scant information exists about their stability. Objective: The aim of the present theoretical study was to explore the role of boron in molecules that combine catecholamines and boric/boronic acids, with a particular interest in examining stability. Method: The methodology was based on the US GAMESS program using DFT with the B3LYP exchange-correlation functional and the 6-31G (d,p) split-valence basis set. Results: According to the current findings, the boron-containing compounds (BCCs) exhibit weaker bonding to the hydroxyls on the ethylamine moiety than to those in the aromatic ring. The strongest binding site of a hydroxyl group was often found to be in meta-position (relative to ethylamine moiety) for boron-free compounds and in para-position for BCCs. Nonetheless, the methyl substituent in the amino group was able to induce changes in this pattern. We analyzed feasible boronsubstituted structures and assessed the relative strength of the respective C-B bonds, which allowed for the identification of the favorable points for reaction and stability. Conclusion: It is feasible to form adducts by bonding on the amine and catechol sides of catecholamines. The presence of boron stabilizes the adducts in para-position. Since some of these BCCs are promising therapeutic agents, understanding the mechanisms of reaction is relevant for drug design.