Mechanistic study of opposite migration order of dimethindene enantiomers in capillary electrophoresis in the presence of native beta-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-beta-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-ethylamin e} (DIM) towards native beta-cyclodextrin (beta-CD) and heptakis(2,3,6-tri- O-methyl-)-beta-CD (TM-beta-CD) were studied using capillary electrophoresi s (CE), NMR spectrometry, electrospray ionization mass spectrometry (ESI-MS ) and X-ray crystallography. NMR spectrometry allowed to estimate the stoic hiometry of the complex and to determine the binding constants. As found us ing ESI-MS, together with more abundant 1:1 complex, a complex with 1:2 sto ichiometry may also be present in a rather small amount in a solution of DI M and beta-CD. One-dimensional ROESY experiments indicated that the geometr y of the complexes of DIM with native beta-CD depends on the ratio of the c omponents in the solution. In the 1:1 solution of DIM and beta-CD the compl ex may be formed by inclusion of the indene moiety of DIM into the cavity o f beta-CD on the primary side and into the cavity of TM-beta-CD into the se condary side. The most likely structural reason for lower affinity of the e nantiomers of DIM towards the cavity of TM-beta-CD compared to native beta- CD could be elucidated. The indene moiety does not enter the cavity of TM-b eta-CD as deeply as the cavity of beta-CD. This may be the most likely expl anation of significantly higher affinity constants of DIM enantiomers towar ds the latter CD compared to the former one. The marked difference between the structure of the complexes may also be responsible for the opposite aff inity pattern of the DIM enantiomers towards beta-CD and TM-beta-CD. (C) 20 00 Elsevier Science B.V. All rights reserved.