Synergistic Effects on Enantioselectivity of Zwitterionic Chiral Stationary Phases for Separations of Chiral Acids, Bases, and Amino Acids by HPLC

Abstract

In an attempt to overcome the limited applicability scope of earlier proposed Cinchona alkaloid-based chiral weak anion exchangers (WAX) and recently reported aminosulfonic acid-based chiral strong cation exchangers (SCX), which are conceptionally restricted to oppositely charged solutes, their individual chiral selector (SO) subunits have been fused in a combinatorial synthesis approach into single, now zwitterionic, chiral SO motifs. The corresponding zwitterionic ion-exchange-type chiral stationary phases (CSPs) in fact combined the applicability spectra of the parent chiral ion exchangers allowing for enantioseparations of chiral acids and amine-type solutes in liquid chromatography using polar organic mode with largely rivaling separation factors as compared to the parent WAX and SCX CSPs. Furthermore, the application spectrum could be remarkably expanded to various zwitterionic analytes such as alpha- and beta-amino acids and peptides. A set of structurally related yet different CSPs consisting of either a quinine or quinidine alkaloid moiety as anion-exchange subunit and various chiral or achiral amino acids as cation-exchange subunits enabled us to derive structure-enantioselectivity relationships, which clearly provided strong unequivocal evidence for synergistic effects of the two oppositely charged ion-exchange subunits being involved in molecular recognition of zwitterionic analytes by zwitterionic SOs driven by double ionic coordination.

Click chemistry immobilization strategies in the development of strong cation exchanger chiral stationary phases for HPLC

“…To address these needs, various chiral stationary phases (CSPs) are available on the market or have recently been developed and employed. Among these, polysaccharide derivatives [1], crown ethers [2][3][4], cyclofructanes [5][6][7], macrocyclic antibiotics [8][9][10], synthetic polymers [11,12] and ion exchange-type CSPs [13,14] have been shown to be efficient in enantiomer separation of racemic amines. Chiral SOs specially developed for enantiomer separation of racemic amines in HPLC [15], supercritical fluid chromatography [16], and CE [17] have been reported as well.…”

Chiral differentiation of some cyclopentane and cyclohexane β-amino acid enantiomers through ion/molecule reactions

“…Chiral crown ether derivatives and ␤-cyclodextrin ( Figure 2) were selected because of their good ability to form host-guest complexes, as well as to recognize and differentiate enantiomers, especially using different chromatographic and mass spectrometric methods [11-17, 28 -35]. The same host compounds were used for both cyclopentane ␤-amino acids (1-4) and cyclohexane ␤-amino acids (5)(6)(7)(8).…”

Study of stereomeric peptoid chiral stationary phases containing different chiral side chains

“…However, with the increasing number of racemates which need to be resolved, novel valuable CSPs are still demanded. For example, CSPs based on oligoproline [9][10][11][12], cyclofructan [13][14][15][16], polymeric diamine derivatives [17][18][19] and zwitterionic cinchona alkaloid [20,21] attract much attention recently.…”