Molecular insights into inclusion complexes of mansonone E and H enantiomers with various β-cyclodextrins

The structural dynamics and stability of inclusion complexes of mansonone E (ME) and H (MH) including their stereoisomers with various βCDs (methylated- and hydroxypropylated-βCDs) were investigated by classical molecular dynamics (MD) simulations and binding free energy calculations. The simulation results revealed that mansonones are able to form inclusion complexes with βCDs. The guest molecules are not completely inserted into the host cavity, their preferably positions are nearby the secondary rim with the oxane ring dipping into the hydrophobic inner cavity. The encapsulation process leads to a higher rigidity of the βCDs enhancing the intramolecular hydrogen bond formation ability and decreasing the chance of glucopyranose rotation. According to the MM-PBSA binding free energy calculation, all considered inclusion complexes are stable and the binding energies are mainly caused by van der Waals interactions. Moreover, the free energy calculations showed significant differences in the complexation energies for the stereoisomers, which could enable the separation of the isomers by analytical techniques for further pharmaceutical applications.