Contrasting binding of fisetin and daidzein in γ-cyclodextrin nanocavity

Steady state and time resolved fluorescence along with anisotropy and induced circular dichroism (ICD) spectroscopy provide useful tools to observe and understand the behavior of the therapeutically important plant flavonoids fisetin and daidzein in γ-cyclodextrin (γ-CDx) nanocavity. Benesi–Hildebrand plots indicated 1:1 stoichiometry for both the supramolecular complexes. However, the mode of the binding of fisetin significantly differs from daidzein in γ-CDx, as is observed from ICD spectra which is further confirmed by docking studies. The interaction with γ-CDx proceeds mainly by the phenyl ring and partly by the chromone ring of fisetin whereas only the phenyl ring takes part for daidzein. A linear increase in the aqueous solubility of the flavonoids is assessed from the increase in the binding of the flavonoids with the γ-CDx cavity, which are determined by the gradual increase in the ICD signal, fluorescence emission as well as increase in fluorescence anisotropy with increasing (γ-CDx). This confirms γ-CDx as a nanovehicle for the flavonoids fisetin and daidzein in improving their bioavailability.

Induced circular dichroism of fisetin (A) and daidzein (C) in γ-CDx matrix. B: Lowest energy docked complex of fisetin (green stick) and daidzein (cyan stick representation) with γ-CDx cavity (yellow line) representations.Figure optionsDownload as PowerPoint slideHighlights
► Fisetin/γ-CDx and daidzein/γ-CDx inclusion complexes were prepared and contrasting binding modes were explored.
► Steady state spectroscopic analyses confirmed the supramolecular interaction of complexes.
► 1:1 Stoichiometry of the complexes of flavonoid-γ-CDx was determined from ICD spectra.
► Increased fluorescence anisotropy and lifetime assures increased solubility of the flavonoids.
► Molecular docking reveals hydrogen bonding primarily dictates the inclusion complex formation.