Complexation of steroid hormones: prednisolone, ethinyloestradiol and estriol with β-cyclodextrin. An aqueous 1H NMR study

摘要

The inclusion complexes of β-cyclodextrin (β-CD) with prednisolone 1, ethinyloestradiol 2 and estriol 3 in aqueousnsolution were investigated using n1nH NMR and molecular modelling. The NMR spectra of the steroids studied in thenpresence of β-CD are fully assigned and interpreted by means of 2D GCOSY and NOESY spectra. The parallelninterpretation of β-CD chemical shift changes and dipolar contacts allows the mode of binding to be established. Onnthe basis of ROESY data, the “low resolution” β-cyclodextrin complexes of 1, 2 and 3 have been determined bynmultistep restrained molecular dynamics calculations. Calculated structures of β-cyclodextrin complexes with 1, 2nand 3 fully agree with experimental data. Combined approaches allow the distinction of weak nonspecific binding forn1 as compared to stronger, “through cavity”, inclusion established for 2 and 3.