Low-molecular-weight chiral cation exchangers: Novel chiral stationary phases and their application for enantioseparation of chiral bases by nonaqueous capillary electrochromatography

Abstract

Cation exchange type chiral stationary phases (CSPs) based on 3,5-dichlorobenzoyl amino acid and amino phosphonic acid derivatives as chiral selectors (SOs) and silica as chromatographic support were developed and applied to enantiomer separations of chiral bases by nonaqueous capillary electrochromatography (NA-CEC). As a rationale for efficient CSP development we adopted the combined use of the "reciprocity principle of chiral recognition" and nonaqueous ion-pair CE as screening assay. Thus, (S)-atenolol was employed as chiral counter-ion added to the BGE in CE and a series of N-derivatized amino acids and amino phosphonic acids were screened to derive reciprocally information on their chiral recognition abilities for atenolol enantiomers. Two SO candidates, namely N-(3,5-dichlorobenzoyl)-O-allyl-tyrosine and N-(4-allyloxy-3,5-dichlorobenzoyl)-1-amino-3-methylbutane phosphonic acid that have been identified as potential SOs in the CE screening were, after immobilization on thiol-modified silica, evaluated in cation-exchange NA-CEC. The strong chiral cation exchanger with the free phosphonic acid group exhibited enhanced enantioselectivity compared to the weak chiral cation exchanger with the carboxylic acid group. A wide variety of chiral bases could be successfully resolved on the strong chiral cation exchanger with alpha-values up to 2.2 and efficiencies up to 375000 m-1 including beta-blockers and other amino alcohols, local anesthetics like etidocaine, antimalarial agents like mefloquine, Tröger's base, phenothiazines like promethazine, and antihistaminics. The influence of several experimental parameters (electrolyte concentration, acid-base ratio and acetonitrile-methanol ratio) was evaluated.

Recent advances in nonaqueous capillary electrophoresis

“…The method was applied in this way to the estimation of chromatographic enantioselectivity of new chiral ion-exchange-type selectors and chiral sta- ACN-MeOH (80:20) Cation exchangers based on N-(3,5-dichloro-benzoyl)-O-allyl-tyrosine and N-(4-allyl-oxy-3,5-dichlorobenzoyl)-1-amino-methylbutane phosphonic acids bonded on thiol-modified silica Chiral bases [131] tionary phases derived from cinchona alkaloid derivatives [116]. A relationship was found between enantioselectivity values in nonaqueous ion-pair CE and ion-exchange chromatography carried out with the identical selectors.…”

Pharmaceutical and biomedical applications of chiral capillary electrophoresis and capillary electrochromatography: An update

“…Except for one investigation on molecular imprint technology [151], all studies published in the reviewed period of time employed capillaries that were obtained by packing with chiral stationary phases or by in situ polymerization yielding monolithic chiral stationary phases. Most separations were carried out in aqueous/ organic background electrolytes although nonaqueous systems were applied as well [137,[139][140][141]. In addition, most chiral selectors studied have been previously used for chiral separation in HPLC.…”

“…A new series of chiral cation-exchange selectors for nonaqueous CEC separations based on 3,5-dichlorobenzoyl amino acid derivatives has been introduced by Lindner's group [141]. The initial selectors were identified via "reciprocal chiral recognition" by nonaqueous ion-pair CE screening of N-derivatized amino acids and amino phosphonic acids using (S)-atenolol as counterion.…”

Sulfated and sulfonated polysaccharide as chiral stationary phases for capillary electrochromatography and capillary electrochromatography–mass spectrometry

“…However, these positively charged polysaccharide CSPs often require multistep synthesis (typically 6–7 steps), which could be very time consuming. Tobler et al [33], Zarbl et al [34] and Hebenstreit et al [35] reported EOF enhancement for brush-type CSPs by introducing small-molecular weight chiral selector with sulfonate or phosphate groups.…”