| Abstract: | Supramolecular interactions between β‐lapachone (β‐lap) and cyclodextrins (CDs) were investigated by isothermal titration calorimetry. The most favorable host: guest interaction was characterized using X‐ray powder diffraction (XRD), differential scanning calorimetry and thermogravimetry (DSC/TG), spectroscopy (FT‐IR), spectroscopy (2D ROESY) nuclear magnetic resonance (NMR), and molecular modeling. Phase solubility diagrams showed β‐, HP‐β‐, SBE‐β‐, γ‐, and HP‐γ‐CDs at 1.5% (w/w) allowed an increase in apparent solubility of β‐lap with enhancement factors of 12.0, 10.1, 11.8, 2.4, and 2.2, respectively. β‐lap has a weak interaction with γ‐ and HP‐γ‐CDs and tends to interact more favorably with β‐CD and its derivatives, especially SBE‐β‐CD (K = 4160 M−1; ΔG = −20.66 kJ·mol−1). Thermodynamic analysis suggests a hydrophobic interaction associated with the displacement of water from the cavity of the CD by the β‐lap. In addition, van der Waals forces and hydrogen bonds were responsible for the formation of complexes. Taken together, the results showed intermolecular interactions between β‐lap and SBE‐β‐CD, thereby confirming the formation of the inclusion complex. Molecular docking results showed 2 main orientations in which the interaction of benzene moiety at the wider rim of the SBE‐β‐CD is the most stable (average docking energy of −7.0 kcal/mol). In conclusion, β‐lap:SBE‐β‐CD is proposed as an approach for use in drug delivery systems in cancer research. |
