Cooperative binding and stabilization of the medicinal pigment curcumin by diamide linked γ-cyclodextrin dimers: A spectroscopic characterization

Diamide linked γ-cyclodextrin (γ-CD) dimers are used to capture curcumin and suppress its decomposition in water. In this study, succinamide and urea linked γ-CD dimers joined through the C6^A carbon on each γ-CD are used. The γ-CD dimers, 66γCD₂su and 66γCD₂ur, show a remarkable ability to suppress the decomposition of curcumin and extend its half-life from less than 30 min to greater than 16 h. The 1:1 association of curcumin with 66γCD ₂su and 66γCD₂ur has high stability constants of 8.7 × 10⁶ M^-1 and 2.0 × 10⁶ M ^-1, respectively. In addition, 2D ¹H NOESY NMR results show specific hydrogen interactions in the association of curcumin with 66γCD₂su and 66γCD₂ur, consistent with the cooperative binding of curcumin by both γ-CD annuli of 66γCD ₂su and 66γCD₂ur. The interactions between curcumin in the linked γ-CD dimers and surfactant micelles were studied using fluorescence spectroscopy. While linked γ-CD dimer-bound curcumin has a negligible fluorescence quantum yield, a significant increase in fluorescence intensity (Φ_fl > 2%) in the presence of micelles suggests that curcumin is delivered to the micelle. The overall results indicate that the diamide linked γ-CD dimers are highly promising systems for curcumin delivery in vivo due to effective curcumin stabilization.