title: NMR and molecular modeling study, as complementary techniques to capillary electrophoresis method to elucidate the separation mechanism of linezolid enantiomers.
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.
authors.affiliation: Nuclear Magnetic Resonance Laboratory, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland. elbed@il.waw.pl
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Bednarek
authors.forename: Wojciech
authors.initials: W
authors.lastname: Bocian
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Michalska
mesh_terms: D000081:Acetamides / Q000737:chemistry / Q000302:isolation & purification*; D000890:Anti-Infective Agents / Q000737:chemistry / Q000302:isolation & purification*; D007202:Indicators and Reagents; D000069349:Linezolid; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D023303:Oxazolidinones / Q000737:chemistry / Q000302:isolation & purification*; D013237:Stereoisomerism
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D007202:Indicators and Reagents; D023303:Oxazolidinones; D000069349:Linezolid