A DFT-Based Mechanism Analysis of the Cyclodextrin Inclusion on the Radical Scavenging Activity of Apigenin

Abstract

Natural flavonoids are renowned for their exceptional antioxidant properties, but their limited water solubility hampers their bioavailability. One approach to enhancing their water solubility and antioxidant activity involves the use of cyclodextrin (CD) inclusion. This study investigated the impact of CD inclusion on the three primary radical scavenging mechanisms associated with flavonoid antioxidant activity, utilizing apigenin as a representative flavonoid and employing density functional theory (DFT) calculations. Initially, the optimized geometries of CD-apigenin inclusion complexes were analyzed, revealing the formation of hydrogen bonds between CD and apigenin. In less polar environments, the inclusion complex strengthened the bond dissociation enthalpies of hydroxyl groups, thereby reducing antioxidant activity. Conversely, in polar environments, the inclusion complex had the opposite effect by lowering proton affinity. These findings align with experimental results demonstrating that CD inclusion complexation enhances flavonoid antioxidant activity in aqueous ethanol solutions.

Keywords: antioxidative activity; apigenin; cyclodextrin inclusion; density functional theory; flavonoid.

Figure 1

The optimized structure of apigenin and the most stable interaction geometries of the α-CD−apigenin complex (A,B) and β−CD−apigenin complex (C,D). To see more clearly about the interaction site, only apigenin and the interaction atom of CD were retained in (C,D). In these figures, the hydrogen, carbon and oxygen atoms are in the off-white, gray and red colors, respectively.

Figure 2

The energies and distributions of HOMO and LUMO orbitals for apigenin in the gas phase. In these figures, the hydrogen, carbon and oxygen atoms are in the off-white, gray and red colors, respectively.