Exploring the inclusion interaction of estradiol with β-CD and HP-β-CD with the help of molecular dynamics simulation as well as multi-spectroscopic approaches

The inclusion behaviors of estradiol with β-CD and HP-β-CD were characterized using molecular dynamics simulation combined with multi-spectroscopic approaches. The findings revealed that estradiol enclosed into the cavity of β-CD and HP-β-CD and produced the estradiol-β-CD and estradiol-HP-β-CD complexes with the stoichiometry of 1:1. The association constants of the estradiol-β-CD and estradiol-HP-β-CD complexes were 3.14 × 10⁴ and 3.22 × 10⁴ M^-1 at 298 K, respectively, which declined with rising temperature. The analysis results of thermodynamic parameters confirmed that the dominate interaction forces were the hydrophobic and hydrogen-bonding interactions for stabilizing the estradiol-β-CD complex, and were the hydrogen bonding interaction and van der Waals forces for stabilizing the estradiol-HP-β-CD complex. Moreover, it was confirmed from the results of molecular modeling that estradiol inserted into the hydrophobic cavity of β-CD and HP-β-CD and form a stable estradiol-CD complexes. And, it is also observed that the phenyl moiety in estradiol is almost parallel to the central axis of β-CD and HP-β-CD, and the phenyl moiety was located on wider rim of β-CD and HP-β-CD.