Complexation of caffeine and theophylline with epigallocatechin gallate in aqueous solution: Nuclear magnetic resonance, molecular docking and thermodynamics studies.

Epigallocatechin gallate (EGCg) and methylxanthines are representative bioactive compounds in tea leaves, the strong affinity between them will elicit destruction of tea quality. In order to elucidate the mechanism of complexation between EGCg and methylxanthines, we compared the bindings of theophylline and caffeine to EGCg by nuclear magnetic resonance (NMR), molecular docking and isothermal titration calorimetry (ITC). The results revealed that the stoichiometries of caffeine to EGCg and theophylline to EGCg were both 1:1. Caffeine and theophylline were captured in the hydrophobic space formed by aromatic rings of EGCg. The affinity between EGCg and caffeine was stronger than that between EGCg and theophylline, which could be partially attributed to the two extra CH-π interactions between N7-Me of caffeine and aromatic rings of EGCg. Furthermore, the results of ITC were agreed well with NMR and molecular docking, indicating that ITC was possible to accurately evaluate the complexation.