Hydrolysis and Enantiodiscrimination of (R)- and (S)-Oxazepam Hemisuccinate by Methylated β-Cyclodextrins: An NMR Investigation

Abstract

Partially and exhaustively methylated β-cyclodextrins [(2-methyl)-β-CD (MCD), heptakis-(2,6-di-O-methyl)-β-CD (DIMEB), and heptakis-(2,3,6-tri-O-methyl)-β-CD (TRIMEB)] have been compared in the hydrolysis and enantiodiscrimination of benzodiazepine derivative (R)- or (S)-oxazepam hemisuccinate (OXEMIS), using nuclear magnetic resonance (NMR) spectroscopy as an investigation tool. After 6 h, MCD induced an 11% hydrolysis of OXEMIS, remarkably lower in comparison with underivatized β-CD (48%), whereas no hydrolysis was detected in the presence of DIMEB or TRIMEB after 24 h. DIMEB showed greater ability to differentiate OXEMIS enantiomers in comparison to TRIMEB, by contrast MCD did not produce any splitting of racemic OXEMIS resonances. Both enantiomers of OXEMIS underwent deep inclusion of their phenyl pendant into cyclodextrins cavities from their wider rims, but tighter complexes were formed by DIMEB with respect to TRIMEB.

Chiral Discrimination Mechanisms by Silylated-Acetylated Cyclodextrins: Superficial Interactions vs. Inclusion

“…In consideration of the quite elusive knowledge to this regard, a great deal of effort has been continuously addressed on the elucidation of the stereochemistry, dynamics, and thermodynamics of the diastereomeric complexes formed by cyclodextrins and enantiomeric substrates [ 4 ]. Such studies can be performed via spectroscopic investigations, mainly nuclear magnetic resonance (NMR) spectroscopy [ 5 , 6 , 7 , 8 ], together with computational methods [ 9 , 10 , 11 , 12 ].…”

NMR Investigation of the Supramolecular Complex Formed by a Phenylboronic Acid-Ferrocene Electroactive Probe and Native or Derivatized β-Cyclodextrin

“…In order to obtain a detailed description on the origin of a receptor selectivity at a molecular level, Nuclear Magnetic Resonance (NMR) spectroscopy represents a powerful and faceted tool that is particularly useful for the deep characterization of cyclodextrins inclusion complexes [ 17 , 18 ], formed with both hydrophilic and lipophilic target molecules [ 19 , 20 , 21 , 22 ].…”