Thermodynamic and structural investigation of curcumin-β-CD inclusion complexes using VT UV/Vis absorption and 2D 1H NOESY NMR

Curcumin, the principal bioactive compound in turmeric, has notable anti-inflammatory, antioxidant, and anticancer properties, but its poor aqueous solubility and low bioavailability limit clinical use. Cyclodextrins (CDs), especially β-cyclodextrin (β-CD) and its derivatives, are promising carriers to enhance the solubility and stability of hydrophobic drugs through host–guest inclusion complexation. In this study, variable-temperature (VT) UV–Vis absorption and 2D 1 H NOESY NMR were used to investigate the thermodynamic and structural features of curcumin complexes with β-CD, (2-hydroxypropyl)-β-CD, and 2,6-di- O -methyl-β-CD. Binding constants (K f ), ΔG°, ΔH°, and ΔS° were determined, showing that complexation is favorable and primarily enthalpy-driven at physiological temperature. Among the β-CDs, 2,6-di- O -methyl-β-CD formed the most stable complex, with K f values two orders of magnitude higher than the others. NOESY spectra confirmed spatial proximity between curcumin and β-CD protons, while peak broadening in 1 H NMR indicated restricted mobility and multiple conformations of curcumin upon encapsulation. These findings offer molecular-level insight into curcumin-β-CD interactions and support the use of 2,6-di- O -methyl-β-CD as an effective delivery system for curcumin. • The most favorable candidate for delivering curcumin is 2,6-di- O -methyl-β-CD among the studied β-CDs. • Method of UV–Vis absorption to determine K f , ΔG°, ΔH° and ΔS° for the formation of curcumin-β-CDs. • Curcumin-β-CD complexations are thermodynamically favorable at physiological temperature. • Predominantly enthalpy-driven for the formation of curcumin-β-CD inclusion complexes. • Method to obtain 2D 1 H NOESY NMR spectra to determine structural inclusion of curcumin-β-CDs.