Metyrapone-β-cyclodextrin supramolecular interactions inferred by complementary spectroscopic/spectrometric and computational studies

Metyrapone was characterized in terms of β-cyclodextrin complexation through a combined experimental and computational approach. Liquid state characterization was carried out by nuclear magnetic resonance spectroscopy and mass spectrometry. 1H NMR and 2D ROESY investigations revealed the inclusion of the metyrapone, speculated by molecular modeling, and the calculated Ka from the DOSY experiments was 408.7 M–1. Molecular dynamics simulations were applied to investigate the thermodynamics and geometry of metyrapone/cyclodextrin inclusion complex. The formation of the complex was also studied at semi-empirical level of theory (PM6). Results of the present study might pave the way for a drug formulation with improved bioavailability and targeting. © 2018 Elsevier B.V.