Premium
Separation of ( Z )‐ and ( E )‐isomers of thioxanthene and dibenz[ b,e ]oxepin derivatives with calixarenes and resorcinarenes as additives in nonaqueous capillary electrophoresis
Author(s) -
Sokoließ Torsten,
Gronau Michael,
Menyes Ulf,
Roth Ullrich,
Jira Thomas
Publication year - 2003
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.200305438
Subject(s) - chemistry , calixarene , capillary electrophoresis , electrophoresis , detection limit , dissociation constant , selectivity , structural isomer , chromatography , stereochemistry , organic chemistry , molecule , biochemistry , receptor , catalysis
Five acidic calix[4]arenes with carboxylic or sulfonic groups at either the upper or lower rim of the cavity and one resorc[4]arene were investigated to separate three thioxanthenes (flupentixol, clopenthixol, chlorprothixene) and a dibenz[ b,e ]oxepin derivative (doxepin) with cis ‐/ trans ‐isomerism by nonaqueous capillary electrophoresis (NACE). Partial filling of the capillary with the UV‐absorbing selectors led to a low detection limit and an advantageous signal‐to‐noise ratio (S/N). A sufficient electrophoretic mobility of the calixarenes towards the anode was necessary to outweigh the oppositely directed electroosmotic flow (EOF). This depended from the functional groups, the dissociation and the hydrodynamic radius of the cyclophanes. In contrast, the resorcinarene was useable only by addition of sodium dodecyl sulfate (SDS) because only the complex of the two selectors had an anodic apparent electrophoretic mobility. p ‐Sulfonyl‐calix[4]arene (ss‐a1) was the most capable selector for all E/Z ‐isomers with maximal α‐values ranging from 1.056 for doxepin to 1.224 for chlorprothixene. This was due to the sufficient migration in reversed direction to the EOF even at low pH* values of 3.0. Otherwise, electrostatic as well as hydrophobic interactions with the positively charged isomers seem to contribute to a superior recognition. Increasing the concentration up to 15 m M ss‐a1 and using acidic media (pH* 5.0) led to high separation efficiency. Changing the organic solvent provides a powerful tool to improve selectivity with N,N ‐dimethylformamide‐methanol (DMF‐MeOH)‐mixtures for thioxanthenes. Further electrophoretic parameters were optimized, such as the concentration of the electrolytes, the addition of SDS, the kind of electrolytes and the voltage. Distinct differences in selectivities were found between the derivatives with thioxanthene and dibenzo[ b,e ]oxepin ring system, respectively. Further, the different basic side chain was responsible for the different selectivity at higher pH* values. In contrast, the substitution at position 2 of the thioxanthenes played a secondary role. Based on the studies of single parameters a method for a simultaneous separation of the four pairs of isomers within 13 min was developed.