NMR and molecular modeling study, as complementary techniques to capillary electrophoresis method to elucidate the separation mechanism of linezolid enantiomers

J Chromatogr A. 2008 Jun 6;1193(1-2):164-71. doi: 10.1016/j.chroma.2008.04.008. Epub 2008 Apr 11.

Abstract

NMR study and molecular modeling were performed to improve the level of understanding of the chiral recognition process occurring between linezolid and anionic single-isomer cyclodextrin-heptakis-(2,3-diacetyl-6-sulfato)-beta-cyclodextrin (HDAS-beta-CD). NMR spectrometry allowed to estimate the stoichiometry of the complexes between HDAS-beta-CD and S- or R-linezolid and to determine the binding constants. The 1:1 complex stoichiometry was detected in millimolar concentrations and the mode of binding was proposed. The binding constants Ka of the complexes were of the order of 30-80 M(-1). Molecular dynamic simulations of 40ns for four complexes and calculations of binding free energies were performed. These calculations allowed determining the mode of binding of linezolid to HDAS-beta-CD and explaining the binding enantioselectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemistry
  • Acetamides / isolation & purification*
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / isolation & purification*
  • Indicators and Reagents
  • Linezolid
  • Magnetic Resonance Spectroscopy / methods*
  • Models, Molecular*
  • Oxazolidinones / chemistry
  • Oxazolidinones / isolation & purification*
  • Stereoisomerism

Substances

  • Acetamides
  • Anti-Infective Agents
  • Indicators and Reagents
  • Oxazolidinones
  • Linezolid