Chiral capillary electrophoresis with cationic pyrrolidinium‐β‐cyclodextrin derivatives as chiral selectors

Abstract

New single-isomer, cationic beta-cyclodextrins, including mono-6-deoxy-6-pyrrolidine-beta-cyclodextrin chloride (pyCDCl), mono-6-deoxy-6-(N-methyl-pyrrolidine)-beta-cyclodextrin chloride (N-CH(3)-pyCDCl), mono-6-deoxy-6-(N-(2-hydroxyethyl)-pyrrolidine)-beta-cyclodextrin chloride (N-EtOH-pyCDCl), mono-6-deoxy-6-(2-hydroxymethyl-pyrrolidine)-beta-cyclodextrin chloride (2-MeOH-pyCDCl) were synthesized and used as chiral selectors in capillary electrophoresis for the enantioseparation of carboxylic and hydroxycarboxylic acids and dansyl amino acids. The unsubstituted pyCDCl exhibited the greatest resolving ability. Most analytes were resolved over a wide range of pH from 6.0 to 9.0 with this chiral selector. In general, increasing pH led to a decrease in resolution. The effective mobilities of all the analytes were found to decrease with increasing CD concentration. The optimal concentration for most carboxylic acids and dansyl amino acid was in the range 5-7.5 mM and >15 mM for hydroxycarboxylic acids. (1)H NMR experiments provided direct evidence of inclusion in the CD cavity.

Recent progress in capillary electrophoretic analysis of amino acid enantiomers

“…On the other hand, various types of cationic CDs have been synthesized and applied to the CDEKC analysis of amino acid racemates [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62]. In contrast to anionic CDs, BGSs with pH 5-8,which is effective for separating neutral amino acids, are applied to EKC using cationic CDs (Table 2).…”

“…When the charged CDs interact with racemic amino acids, the analytes migrate at a different velocity from a surrounding aqueous phase due to the electrophoretic migration of the ionic CDs. Although various anionic [34][35][36][37][38][39][40][41][42][43] and cationic CDs [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] are synthesized for CDEKC as summarized in Table 2, sulfated CDs (S-CDs) [34,35] and highly sulfated CDs (HS-CDs) [36][37][38][39][40][41] are still the predominant CSs due to their resolution powers and commercial-availability. Since commercially available S-CDs and HS-CDs from Beckmann Coulter are not single isomers but a mixture of sulfated CDs with a different degree of substitution (average; 9 and 12, respectively), a wide range of OTG, 1-S-octyl-␤-d-thioglucopyranoside; DTDP, 3-(4,6-dichloro-1,3,5-triazinylamino)-7-dimethyamino-2-methylphenazine; LED-IF, light-emitting diode-induced fluorescence.…”

Recent development of cationic cyclodextrins for chiral separation

“…Considering the existence of three types of hydroxyl groups located on the CD rims, the structurally simplest cationic CDs, mono-6 or 2-amino-CDs, were easily prepared with triphenylphosphine-catalyzed reduction of azido-CDs and a further hydrolysis [22]. Starting from mono-tosylated CDs, the nucleophilic attack by alkylimidazole [23], alkylamine [24] and alkylpyrrodine [25] can afford different series of mono-substituted cationic CDs.…”

Chiral electromigration techniques in pharmaceutical and biomedical analysis

“…Optimum separation conditions were achieved at a CD concentration of 10 mM. A series of single isomer quaternary pyrrolidinium-β-CD derivatives were synthesized by Xiao and colleagues [61] including mono-6-deoxy-6-pyrrolidinium-β-CD, mono-6-deoxy-6-(N-methyl-pyrrolidinium)-β-CD, mono-6-deoxy-6-(N-(2-hydroxyethyl)-pyrrolidinium)-β-CD and mono-6-deoxy-6-(2-hydroxymethylpyrrolidinium)-β-CD. The highest resolution was achieved for dansyl-amino acids and carboxylic and hydroxycarboxylic acids using mono-6-deoxy-6-pyrrolidinium-β-CD as chiral selector in the pH range 6.0-9.0.…”