Characterization of the inclusion interaction of ethinyloestradiol with β-cyclodextrin and hydroxypropyl-β-cyclodextrin: Multi-spectroscopic and molecular modeling methods

In this work, the inclusion interactions between ethinyloestradiol (EE) and beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were characterized through absorption spectroscopy (UV), fluorescent spectrometry (FS), Fourier transform infrared spectroscopy (FT-IR), circular dichroism (CD), nuclear magnetic resonance spectroscopy (NMR), and molecule modeling methods for clarifying its inclusion mechanism with cyclodextrins (CDs). The results suggested that the inclusion constants (K) of the EE/beta-CD and EE/HP-beta-CD complexes with the stoichiometry of 1:1 were 6.63 x 10(4) and 3.82 x 10(4) M-1 at 298 K, respectively. The thermodynamic analysis revealed that EE spontaneously inserted into the cavity of CDs such as beta-CD and HP-beta-CD. In the EE and beta-CD system, the primary driving forces are van der Waals and hydrogen bonding interaction, whereas the main driving forces in the EE and HP-beta-CD system are hydrophobic interaction and hydrogen-binding interactions. The molecular simulation findings further confirmed that EE inserts into the cavity of CDs. D-ring was located in the narrow edge of CDs while benzene ring was located in the wider edge of CDs cavity. And, the inclusion interaction between the two causes the change in both conformations, especially, the HP-beta-CD conformation. This paper also confirmed that interaction of complex result in the change in the physicochemical natures of EE. (C) 2020 Elsevier B.V. All rights reserved.