Molecules (Oct 2021)

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

  • Andrea Cesari,
  • Federica Balzano,
  • Gloria Uccello Barretta,
  • Alessandra Recchimurzo

DOI
https://doi.org/10.3390/molecules26216347
Journal volume & issue
Vol. 26, no. 21
p. 6347

Abstract

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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.

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