Last ten years (2008–2018) of chiral ligand‐exchange chromatography in HPLC: An updated review

Abstract

Chiral ligand-exchange chromatography is one of the elective strategies for the direct enantioresolution of small chelating compounds: amino acids, diamines, amino alcohols, diols, small peptides, etc. Unlike other methods, the interaction between chiral selector and analyte enantiomers is mediated by a cation, thus producing diastereomeric ternary complexes. Two main approaches are conventionally applied in chiral ligand-exchange chromatography. The first relies upon chiral stationary phases where the chiral selector is either covalently immobilized or physically adsorbed onto suitable packing materials (coated phases). In the second approach, chiral molecules are added to the eluent, thus generating chiral eluent systems. Among the advantages of chiral ligand-exchange chromatography, the generation of UV/vis-active metal complexes, and the use of commercially available or easy-to-synthesize chiral selectors, in combination to rather inexpensive achiral columns for coated phases and chiral eluents, are noteworthy. Besides amino acids and amino alcohols, other species have proven suitable for chiral ligand-exchange chromatography applications. Recently, the use of either chiral ionic liquids or micellar liquid chromatography systems as well as the successful off-column formation of diastereomeric complexes have expanded the selectivity profiles and application fields. All of these issues are touched in the review, shedding light to the contributions appeared in the last decade.

Comprehensive Online Reversed-Phase × Chiral Two-Dimensional Liquid Chromatography-Mass Spectrometry with Data-Independent Sequential Window Acquisition of All Theoretical Fragment-Ion Spectra-Acquisition for Untargeted Enantioselective Amino Acid Analysis

“…In general, this 2DLC method can provide a first assessment of concentration levels and AA stoichiometries in peptide hydrolysates, but further advancement of the method for improvement of accuracy and precision is recommended. This should be possible with the inclusion of 13 C-labeled IS (not included in this quantitative analysis). To avoid extensive calibration runs, future focus will be to incorporate internal calibration with 13 C-ISs for accurate quantification as suggested recently.…”

“…This should be possible with the inclusion of 13 C-labeled IS (not included in this quantitative analysis). To avoid extensive calibration runs, future focus will be to incorporate internal calibration with 13 C-ISs for accurate quantification as suggested recently. 56 For accurate trace-level enantiomeric impurity determination, the current method is not suitable yet.…”

“…They are also present in (natural, synthetic, and therapeutic) peptides, requiring their analytical determination as part of structure elucidation and/or quality control . A direct enantioresolution of underivatized and derivatized AAs using chiral stationary phases is nowadays the first choice. − Common examples for achiral precolumn derivatization supporting chiral separation comprise 6-aminoquinolyl- N -hydroxysuccinimidyl carbamate (AQC), , 1-fluoro-2,4-dinitrobenzene (DNB-F, Sanger’s reagent), 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD), dansyl chloride (Dns), , and 9-fluorenylmethyl-chloroformate (Fmoc-Cl). − These reagents commonly improve the retention and enantioselective behavior, , introduce chromophoric and fluorophoric detectability, can enhance detection sensitivity of AAs with poor electrospray ionization efficiency, and deliver signature ions (in MS/MS detection). , Chiral stationary phases, the workhorses for direct HPLC enantiomer separation, have often remarkable enantioselectivity, but suffer from limited chemoselectivity and lower efficiencies (compared to highly efficient RP congeners). , Hence, the combination of the two principles is quite obvious and should lead to an enhanced separation technology platform.…”

Macromolecular helicity induction and static helicity memory of poly(biphenylylacetylene)s bearing aromatic pendant groups and their use as chiral stationary phases for high‐performance liquid chromatography

“…Direct enantioseparation by high-performance liquid chromatography (HPLC) and supercritical fluid chromatography with chiral stationary phases (CSPs) [1][2][3][4][5][6][7][8][9][10] is recognized as one of the most powerful and widely used techniques for both the trace analyses of chiral molecules and industrial-scale productions of optically pure ingredients. [11][12][13][14][15][16][17][18][19] Okamoto et al achieved the first asymmetric synthesis of a one-handed helical poly(triphenylmethyl methacrylate) (PTrMA) [20][21][22][23][24][25] by the helix-sense-selective polymerization of an achiral bulky vinyl monomer with a chiral catalyst in 1979 and discovered its remarkable chiral separation ability when used as a CSP for HPLC, which was then commercialized in [This article is part of the Special Issue: A Special Issue to Celebrate the 80th Birthday of Professor Yoshio Okamoto.…”

Enantioseparation of phenethylamines by using high‐performance liquid chromatography column permanently coated with methylated β‐cyclodextrin

“…Enantiomers of many compounds have been separated by chiral HPLC based on direct method without derivatization of analyte and indirect methods with chiral derivatization [1–9]. The most used chiral HPLC is direct methods with chiral columns, where enantiomeric separation is based on reversible diastereomeric association between the chiral functional groups on the stationary phase and enantiomers of analytes.…”