Host–guest complexation of omeprazole, pantoprazole and rabeprazole sodium salts with cyclodextrins: an NMR study on solution structures and enantiodiscrimination power

Abstract

The application of different cyclodextrins (CDs) as NMR chiral solvating agents (CSAs) for the sodium salts of the proton-pump inhibitors omeprazole, pantoprazole (sesquihydrate) and rabeprazole was investigated. It was proved that the formation of diastereomeric host–guest complexes in D2O solution between the CDs and those substrates permitted the direct 1H NMR discrimination of the enantiomers of the sodium salts of these compounds without the need of previous working-up. Rotating frame nuclear overhauser effect spectroscopy (ROESY) was used to ascertain the solution geometries of the host–guest complexes. The results suggested a preferential binding of the benzimidazole moiety of the guest molecules within the macrocyclic cavity of α-CD, whereas the higher dimensions of β- and γ-CD also permitted the inclusion of the highly substituted pyridine moieties. Moreover, the solution stoichiometries and the binding constants of the complexes formed with pantoprazole at room temperature were determined by 1H and 19F NMR titration. Diffusion-filtered Spectroscopy was applied to obtain clean spectra without the interference of the HOD signal.