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 D 2 O solution between the CDs and those substrates permitted the direct 1 H 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 a-CD, whereas the higher dimensions of b-and c-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 1 H and 19 F NMR titration. Diffusion-filtered Spectroscopy was applied to obtain clean spectra without the interference of the HOD signal.

Insight into old and new pure shift nuclear magnetic resonance methods for enantiodiscrimination

“…Reproduced from Chaudhari [39] acquisition (see Figure 4c) to cause magnetization transfer to other protons in bonding network like in TOCSY experiment. [65] One advantage of these experiments is that they require very small spectral width (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) in the indirect dimensions. Consequently, these experiments are fast, and sufficient line narrowing between the spectral lines is achievable in a small number of increments.…”

“…Ever since the seminal work of Cram and co‐workers, NMR spectroscopic methods have offered a powerful analytical tool, complementing other chiroptical methods, for testing enantiopurity, measurement of ee , and determination of absolute configuration . Under isotropic achiral conditions, NMR spectroscopy is unable to differentiate enantiomers, unless the intermolecular diastereomeric interactions are imposed with an enantiomerically pure reagent called chiral auxiliary . The chiral auxiliaries such as chiral solvating agents (CSAs), chiral derivatizing agents, and chiral lanthanide shift reagents (CLSRs) in isotropic solvents are utilized to distinguish enantiomers.…”

“…[8,[15][16][17][18] Under isotropic achiral conditions, NMR spectroscopy is unable to differentiate enantiomers, unless the intermolecular diastereomeric interactions are imposed with an enantiomerically pure reagent called chiral auxiliary. [19][20][21][22][23] The chiral auxiliaries such as chiral solvating agents (CSAs), chiral derivatizing agents, and chiral lanthanide shift reagents (CLSRs) in isotropic solvents are utilized to distinguish enantiomers. Chiral auxiliaries utilize the chemical shift difference between the enantiomeric resonances to visualize enantiomers due to the formation of two species (at least) between them.…”

Structure Elucidation of Benzhexol-<i>β</i>-Cyclodextrin Complex in Aqueous Medium by <sup>1</sup>H NMR Spectroscopic and Computational Methods

“…Direct evidence for the formation of inclusion complexes is obtained by simply comparing the 1 H NMR data of pure host and guest with that of a mixture of host and guest [18]. There are several reports on the NMR studies of CDs inclusion complexes and it is considered best technique for such studies in solution [19] [20]. Chemical shift changes (Δδ) for the protons of both host as well as guest are studied.…”

Chiral separation of lansoprazole and rabeprazole by capillary electrophoresis using dual cyclodextrin systems

“…Based on previously published articles regarding chiral separation of PPI by CE and on other studies regarding CD complexation of PPIs ; CD derivatives seem the most promising candidates as chiral selectors for the enantioseparation of lansoprazole and rabeprazole. Moreover, SBE‐β‐CD was applied for the chiral separation of the structurally similar pantoprazole in CE as well as in HPLC as chiral mobile phase additive.…”