Supramolecular interactions between β-lapachone with cyclodextrins studied using isothermal titration calorimetry and molecular modeling

Supramolecular interactions between beta-lapachone (beta-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 beta-, HP-beta-, SBE-beta, gamma-, and HP-gamma-CDs at 1.5% (w/w) allowed an increase in apparent solubility of beta-lap with enhancement factors of 12.0, 10.1, 11.8, 2.4, and 2.2, respectively. beta-lap has a weak interaction with gamma- and HP-gamma-CDs and tends to interact more favorably with beta-CD and its derivatives, especially SBE-beta-CD (K=4160M(-1); Delta G=-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 beta-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 beta-lap and SBE-beta-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-beta-CD is the most stable (average docking energy of --7.0 kcal/mol). In conclusion, beta-lap:SBE-beta-CD is proposed as an approach for use in drug delivery systems in cancer research.