Epicatechin-Diarylboronate Aggregates with Inhibited Auto-oxidation and Stable Antioxidant Activity: Structural Modification and Binding Thermodynamics

Improving the stability of catechins against autoxidation and simultaneously exerting their biological activity to scavenge reactive oxygen species (ROS) are essential for achieving their efficient utilization in healthcare and drug therapy. Focusing on this important objective, a feasible strategy for modifying catechins with arylboronic acid has been proposed as they have good biocompatibility and also controllable release at specific sites. We developed three catechin-diarylboronate (DiarylBA) ester self-assembly carriers, in which DiarylBA serves as the receptor molecules of catechins, including a coupled benzyl ammonium boronic acid (BTEAB) or two coupled pyridinium boronic acids (PyBBA and PyPBA) linked by a spacer, and (-)-epicatechin (EC) is taken as the representative catechin molecule. Specifically, the inhibition of the auto-oxidation and the antioxidant activities for both EC and EC-DiarylBA esters were characterized sufficiently by combining spectroscopies (UV-vis, NMR), and ROS scavenging assessment. The relevant binding thermodynamics and interaction mechanism, as well as their aggregation behavior, were also studied by ITC, NMR, and light scattering. The thermodynamic and spectroscopic results all confirm the generation of EC-DiarylBA esters in a range from a weak acid of pH 6.5 to an alkaline one of pH 8.5. It was found that the esterification of EC with DiarylBA can effectively inhibit the auto-oxidation of EC even at pH 8.5 and still retain the excellent antioxidant activity of the original EC. Furthermore, the EC-BTEAB ester exhibits a favorable H2O2 responsiveness in the H2O2-overexpressed site, while EC-PyBBA and EC-PyPBA esters need to first release the EC component to effectively eliminate H2O2. Therefore, the comprehensive results of stability and antioxidant activity indicate that the EC-DiarylBA ester would be a promising candidate for enhancing EC's medicinal and health care effects.