Separation of (Z)‐ and (E)‐isomers of thioxanthene and dibenz[b,e]oxepin derivatives with calixarenes and resorcinarenes as additives in nonaqueous capillary electrophoresis

Abstract

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 alpha-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 mM 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.

Subcellular metabolite profiles of the parent CCRF-CEM and the derived CEM/C2 cell lines after treatment with doxorubicin

“…The observed mobility ratio (OMR), which is determined by dividing the observed electrophoretic mobility (OM) of the metabolite by the observed electrophoretic mobility of DOX, was also calculated since it is generally believed that systematic alterations in partitioning between the aqueous and micellar phase may be reduced when this parameter is used. Similar correction procedures have previously resulted in an improvement in migration time and electrophoretic mobility reproducibilities [27][28][29][30][31][32].…”

Capillary electrophoresis in N,N‐dimethylformamide

“…, and zone electrophoresis of inorganic anions [7] and drugs (sometimes in a binary mixture with ,6% acetic acid) [8][9][10][11][12]. It has been used in chiral separations [13][14][15][16], in capillary electrochromatography of retinyl esters (in a mixture with 1% methanol) [17], in capillary size exclusion electrochromatography [18][19][20], in capillary gel electrophoresis of neutral polymers (mostly in mixtures with 1-6% water) [21], and in other applications [22][23][24][25][26]. Its influence on the electroosmotic flow (EOF) has been studied in both uncoated [7,[27][28][29][30] …”

Enhanced binding and conformational selectivity in affinity capillary electrophoresis using a water‐soluble resorcin[4]arene as intrinsic buffer and electrokinetic host

“…They also serve as useful precursors for constructing conformationallyrigid cavitands [15], and noncovalent resorcinarene capsule assemblies [16]. There have been several reports of using charged resorcin [4]arenes as novel additives for separation of neutral analytes by CE [17][18][19][20], however quantitative understanding of their interaction by ACE has yet to be explored. In this study, the C-tetraethylsulphonate derivative of 2-methyl resorcinarene (TESMR) was used as the host because of its high aqueous solubility, large negative mobility and flexible structure for accommodating a variety of guests [19,21].…”