Interaction of cinnamic acid derivatives with β-cyclodextrin in water: Experimental and molecular modeling studies

Cyclodextrins (CDs) can be used to improve the solubility and stability of cinnamic acid derivatives (CAs). However, there was no detailed report about understanding the effects of the substituent groups in the benzene ring on the inclusion behavior between CAs and CDs in aqueous solution. Here, the interaction of β-CD with CAs, including caffeic acid, ferulic acid, and p -coumaric acid, in water was investigated by phase-solubility method, UV, fluorescence, and 1 H NMR spectroscopy, together with ONIOM (our Own N-layer Integrated Orbital molecular Mechanics)-based QM/MM (Quantum Mechanics/Molecular Mechanics) calculations. Experimental results demonstrated that CAs could form 1:1 stoichiometric inclusion complex with β-CD by non-covalent bonds, and that the maximum apparent stability constants were found in caffeic acid (176   M −1 ) followed by p -coumaric acid (160   M −1 ) and ferulic acid (133   M −1 ). Moreover, our calculations reasonably illustrated the binding orientations of β-CD with CAs determined by experimental observations.