ENANTIOSEPARATION OF MIANSERINE ANALOGS USING CAPILLARY ELECTROPHORESIS WITH NEUTRAL AND CHARGED CYCLODEXTRIN BUFFER MODIFIERS - C-13 NMR-STUDY OF THE CHIRAL RECOGNITION MECHANISM

The enantiomers of the antidepressant drug xahydro-2-methyldibenzo[c,f ]pyrazino[1,2-a]azepine (mianserine, Tolvin) [(+/-)-MN] and its 11 str uctural analogues were resolved with capillary electrophoresis (CE) us ing native beta-cyclodextrin (beta-CD) and three charged CD-derivative s as chiral buffer modifiers. The effect of the nature and position of substituents of the chiral solute on the resolution is discussed. Sul fonated beta-CD derivatives such as sulfobutyl (SBE-beta-CD) and sulfo ethyl (SEE-beta-CD) ethers of beta-CD permit adequate enantioseparatio ns at rather lower concentrations as chiral selectors in comparison wi th carboxymethyl-beta-CD (CM-beta-CD) and especially with native beta- CD. In a previous paper, we ascribed the high chiral resolving power o f SBE-beta-CD to the counter-current mobility of this chiral selector. Another important advantage of SBE--CD, its more stereoselective bind ing to the chiral selectand, is proved here on the basis of C-13 NMR s tudies. This last technique seems to be useful for estimation of the s toichiometry of the host-guest complexes as well as for determination of the apparent binding constants. A number of well-resolved C-13 NMR signals which belong to the CD complexes with the (+/-)- or (-)-enanti omer of the chiral solute enable racemic samples to be used for the st udy of the enantioselective binding parameters. Additionally, these CD derivatives can be recommended as useful water-soluble chiral shift r eagents for the enantiomeric excess determination by C-13 NMR techniqu e.