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Supramolecular interactions between β‐lapachone with cyclodextrins studied using isothermal titration calorimetry and molecular modeling
Author(s) -
XavierJunior Francisco H.,
Rabello Marcelo M.,
Hernandes Marcelo Z.,
Dias Marília E.S.,
Andrada Otoni H.M.S.,
Bezerra Beatriz P.,
Ayala Alejandro P.,
SantosMagalhães Nereide S.
Publication year - 2017
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.2646
Subject(s) - isothermal titration calorimetry , chemistry , differential scanning calorimetry , supramolecular chemistry , van der waals force , hydrogen bond , crystallography , thermogravimetry , intermolecular force , solubility , calorimetry , hydrophobic effect , moiety , molecule , stereochemistry , organic chemistry , crystal structure , inorganic chemistry , thermodynamics , physics
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.