Enantioselective stabilization of inclusion complexes of metoprolol in carboxymethylated β-cyclodextrin

The inclusion complexes of metoprolol (MT) and carboxymethyl-beta-cyclodextrin (CMCD) were prepared and the stability constants of the complexes were determined. Binding studies performed using high performance liquid chromatography (HPLC), UV spectrometry and capillary electrophoresis (CE) indicated that a complex with 1:1 stoichiometry is predominant in the solution. The enantiomers of MT possess relatively high affinity towards CMCD with stability constants of 288 and 262 per M for (R)- and (S)-MT, respectively. Through nuclear magnetic resonance (NMR) analysis, MT was predicted to be a bent structure with phenyl ring of MT inserted in the shielding cavity of CMCD during complex formation. The NMR data suggested that the chiral side chain and the methoxyethyl moiety of MT are aligned in the deshielding zone, above and below the CMCD torus ring. (C) 2002 Elsevier Science B.V. All rights reserved.