Mechanistic study of opposite migration order of dimethindene enantiomers in capillary electrophoresis in the presence of native β-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin

The possible mechanisms of the opposite affinity pattern of the enantiomers of dimethindene {(R,S)-N,N-dimethyl-3[1(2-pyridyl)ethyl]indene-2-ethylamine} (DIM) towards native β-cyclodextrin (β-CD) and heptakis(2,3,6-tri-O-methyl-)-β-CD (TM-β-CD) were studied using capillary electrophoresis (CE), NMR spectrometry, electrospray ionization mass spectrometry (ESI-MS) and X-ray crystallography. NMR spectrometry allowed to estimate the stoichiometry of the complex and to determine the binding constants. As found using ESI-MS, together with more abundant 1:1 complex, a complex with 1:2 stoichiometry may also be present in a rather small amount in a solution of DIM and β-CD. One-dimensional ROESY experiments indicated that the geometry of the complexes of DIM with native β-CD depends on the ratio of the components in the solution. In the 1:1 solution of DIM and β-CD the complex may be formed by inclusion of the indene moiety of DIM into the cavity of β-CD on the primary side and into the cavity of TM-β-CD into the secondary side. The most likely structural reason for lower affinity of the enantiomers of DIM towards the cavity of TM-β-CD compared to native β-CD could be elucidated. The indene moiety does not enter the cavity of TM-β-CD as deeply as the cavity of β-CD. This may be the most likely explanation of significantly higher affinity constants of DIM enantiomers towards the latter CD compared to the former one. The marked difference between the structure of the complexes may also be responsible for the opposite affinity pattern of the DIM enantiomers towards β-CD and TM-β-CD.