SCREENING OF CYCLODEXTRINS BY NUCLEAR-MAGNETIC-RESONANCE FOR THE DESIGN OF CHIRAL CAPILLARY ELECTROPHORESIS SEPARATIONS

High-field one-dimensional (1D) and two-dimensional (2D) nuclear magne tic resonance (NMR) spectroscopy and capillary electrophoresis (CE) ar e examined to investigate the process of chiral recognition occurring between different cyclodextrins (CDs) and the racemic anti-schistosomi asis drug, oxamniquine. Five neutral CDs (alpha-CD, beta-CD, gamma-CD, hydroxypropyl-beta-CD and hydroxyethyl-beta-CD) and two anionic CDs, carboxymethyl-beta-CD (CM-beta-CD) and sulphobutyl ether-beta-CD (SBE- beta-CD) were selected for these NMR and CE studies. Three batches of the anionic CD [SBE-beta-CD(7), SBE-beta-CD(4) and SBE-beta-CD(1)] dif fering in their degree of substitution (6.5, 4.5 and 1.0, respectively ), were also examined in these studies. In the 1D NMR studies, the shi ft displacement values (Delta delta Hz), after addition of each of the nine CDs in a 1:I molar ratio, the diagnostic aromatic singlets indic ated interaction between oxamniquine and each of the CDs. With regard to shift non-equivalence (Delta delta) for the two aromatic singlets, the anionic CDs were the only agents to show any interaction. It was also found that by manipulating the sample pH value, the ionic state o f both selector and selectand had an influence on the enantiorecogniti on process. The complex between oxamniquine and the SBE-beta-CD(7) was subsequently examined using 2D rotating frame nuclear Overhauser effe ct spectroscopy (ROESY), and the complexation process was found to inv olve an inclusion mechanism. Spin-lattice relaxation time (T-1) measur ements confirmed this observation. In the CE studies, each of the nine CDs was examined as a chiral electrolyte additive for the enantiosepa ration of racemic oxamniquine. Complete separation was not found when using any of the neutral CDs, but in contrast to the anionic CDs, CM-b eta-GD and the SBE-beta-CD(4), displayed a 95 and 100% separation, res pectively. Interestingly, the higher and lower derivatised SBE-beta-CD selectors yielded 10% and zero separation, respectively. This is stro ng evidence that the degree of substitution has a critical effect on t he enantiorecognition process. Good correlation between the NMR shift non-equivalence data for oxamniquine and the degree of enantioseparati on was observed in CE. The neutral CDs displayed no shift non-equivale nce for oxamniquine and no enantioseparation was found. However, for t he anionic CDs a significant shift non-equivalence was observed and th is corresponded to a significant enantioseparation in CE. (C) 1998 Els evier Science B.V.