This contribution reports the synthesis, characterization and capillary electrophoretic application of heptakis-(6-O-sulfobutyl-ether)-β-cyclodextrin sodium salt, (6-(SB)7-β-CD). The compound was obtained through a five-steps synthesis and it represents the first example of single-isomer sulfobutylated cyclodextrin that carries the negatively charged functions exclusively on its primary side and it is unmodified on the lower rim. The purity of each intermediate was determined by appropriate liquid chromatographic methods, while the isomeric purity of the final product was established by an ad-hoc developed HPLC method based on a CD-Screen-IEC column. The structural identification of 6-(SB)7-β-CD was carried out by 1D, 2D NMR spectroscopy and ESI-MS. The chiral separation ability of 6-(SB)7-β-CD was studied by chiral capillary electrophoresis using the single-isomer host as a background electrolyte additive to separate the enantiomers of a representative set of pharmacologically significant model compounds such as verapamil, dapoxetine, ondansetron, propranolol, atenolol, metoprolol, carvedilol, terbutaline, amlodipine and tadalafil. The enantiomer migration order and the effects of the selector concentration on the enantiorecognition properties were investigated. NMR spectroscopy was applied to deepen and further confirm the host-guest interactions and in the case of the model compound dapoxetine a potential representation for the supramolecular assembly was developed based on the dataset collected by the extensive 2D NMR analysis. This single-isomer chiral selector offers a new alternative to the widely applied randomly sulfobutylated- and sulfated-beta-cylodextrins as well as to the single-isomer sulfated and carboxymethylated derivatives in chiral separations.

• MeSH
• beta-Cyclodextrins analysis   chemical synthesis   chemistry   MeSH
• Electrophoresis, Capillary methods   MeSH
• Electrolytes MeSH
• Spectrometry, Mass, Electrospray Ionization MeSH
• Hydrogen-Ion Concentration MeSH
• Magnetic Resonance Spectroscopy MeSH
• Stereoisomerism MeSH
• Chromatography, High Pressure Liquid MeSH
• Publication type
• Journal Article MeSH

Enantiomers of (+/-) 5-[2 (R,S)-{[2-(o-ethoxyphenoxy) ethyl] amino} propyl]-2-methoxy-benzenesulfonamide (tamsulosin, drug frequently used in the treatment of prostate diseases) were separated by capillary electrophoresis (CE). An acidic background electrolyte (BGE) with sulfated-beta-cyclodextrin (S-beta-CD) was used to create a chiral separation environment. Baseline separation of the isomers was achieved during 5 min using cathodic electro-osmotic flow (EOF) (countercurrent mode). The quantification limits were 5.3 x 10(-6) moll(-1) for R-isomer and 5.7 x 10(-6) moll(-1) for S-isomer. The R.S.D. values of peak area were 0.54% for R-isomer and 0.75% for S-isomer. The results achieved enable determination of 0.5% of optical impurity.

• MeSH
• Acetonitriles analysis   MeSH
• Adrenergic alpha-Antagonists analysis   chemistry   MeSH
• beta-Cyclodextrins analysis   chemistry   MeSH
• Time Factors MeSH
• Models, Chemical MeSH
• Electrophoresis, Capillary methods   instrumentation   MeSH
• Electrophoresis MeSH
• Electrolytes MeSH
• Financing, Organized MeSH
• Furans analysis   chemistry   MeSH
• Calibration MeSH
• Acetic Acid chemistry   MeSH
• Osmosis MeSH
• Reproducibility of Results MeSH
• Sulfur chemistry   MeSH
• Stereoisomerism MeSH
• Sulfonamides analysis   chemistry   MeSH
• Chromatography, High Pressure Liquid MeSH
• Dose-Response Relationship, Drug MeSH