Chiral electromigration techniques in pharmaceutical and biomedical analysis

Scriba, Gerhard K. E.

doi:10.1007/s12566-011-0024-3

Cited by 11 publications

(11 citation statements)

References 156 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[3][4][5][6][7][8] Typically, chiral separations are achieved via liquid or gas chromatography, but optimizations and analysis using these separations can often be long and tedious. [9][10][11] In an effort to eliminate these slow and tedious steps, there has been significant interest in the development of methods that enable chiral discrimination in mass spectrometry (MS). However, isomeric species have the same exact mass, making it impossible to differentiate these ions by m/z alone.…”

Section: Introductionmentioning

confidence: 99%

Structural Resolution of 4-Substituted Proline Diastereomers with Ion Mobility Spectrometry via Alkali Metal Ion Cationization

2015

View full text Add to dashboard Cite

The chirality of substituents on an amino acid can significantly change its mode of binding to a metal ion, as shown here experimentally by traveling wave ion mobility spectrometry-mass spectrometry (TWIMS-MS) of different proline isomeric molecules complexed with alkali metal ions. Baseline separation of the cis- and trans- forms of both hydroxyproline and fluoroproline was achieved using TWIMS-MS via metal ion cationization (Li(+), Na(+), K(+), and Cs(+)). Density functional theory calculations indicate that differentiation of these diastereomers is a result of the stabilization of differing metal-complexed forms adopted by the diastereomers when cationized by an alkali metal cation, [M + X](+) where X = Li, Na, K, and Cs, versus the topologically similar structures of the protonated molecules, [M + H](+). Metal-cationized trans-proline variants exist in a linear salt-bridge form where the metal ion interacts with a deprotonated carboxylic acid and the proton is displaced onto the nitrogen atom of the pyrrolidine ring. In contrast, metal-cationized cis-proline variants adopt a compact structure where the carbonyl of the carboxylic acid, nitrogen atom, and if available, the hydroxyl and fluorine substituent solvate the metal ion. Experimentally, it was observed that the resolution between alkali metal-cationized cis- and trans-proline variants decreases as the size of the metal ion increases. Density functional theory demonstrates that this is due to the decreasing stability of the compact charge-solvated cis-proline structure with increased metal ion radius, likely a result of steric hindrance and/or weaker binding to the larger metal ion. Furthermore, the unique structures adopted by the alkali metal-cationized cis- and trans-proline variants results in these molecules having significantly different quantum mechanically calculated dipole moments, a factor that can be further exploited to improve the diastereomeric resolution when utilizing a drift gas with a higher polarizability constant.

show abstract

Section: Introductionmentioning

confidence: 99%

Structural Resolution of 4-Substituted Proline Diastereomers with Ion Mobility Spectrometry via Alkali Metal Ion Cationization

2015

View full text Add to dashboard Cite

show abstract

“…Different enantiomers of a bioactive molecule frequently show substantially different biological effects, thus their enantioselective synthesis, pharmacological study, and chiral analysis are of fundamental interest. To control the enantiomeric purity, the development of sensitive, selective, fast, and robust methods is important []. As capillary electrophoresis eminently meets all these requirements, it has rapidly been established as one of the major techniques for analytical‐scale enantioseparations [].…”

Section: Introductionmentioning

confidence: 99%

Chiral recognition of imperanene enantiomers by various cyclodextrins: A capillary electrophoresis and NMR spectroscopy study

et al. 2012

View full text Add to dashboard Cite

The enantiomers of imperanene, a novel polyphenolic compound of Imperata cylindrica (L.), were separated via cyclodextrin-modified capillary electrophoresis. The anionic form of the analyte at pH 9.0 was subject to complexation and enantioseparation CE studies with neutral and charged cyclodextrins. As chiral selectors 27 CDs were applied differing in cavity size, sidechain, degree of substitution (DS) and charge. Three hydroxypropylated and three sulfoalkylated CD preparations provided enantioseparation and the migration order was successfully interpreted in each case in terms of complex mobilities and stability constants. The best enantioresolution (R(S) = 1.26) was achieved using sulfobutyl-ether-γ-CD (DS ∼4), but it could be enhanced by extensive investigations on dual selector systems. After optimization (CD concentrations and pH) R(S) = 4.47 was achieved using a 12.5 mM sulfobutyl-ether-γ-CD and 10 mM 6-monodeoxy-6-mono-(3-hydroxy)-propylamino-β-cyclodextrin dual system. The average stoichiometry of the complex was determined with Job's method using NMR-titration and resulted in a 1:1 complex for both (2-hydroxy)propyl-β- and sulfobutyl-ether-γ-CD. Further NMR experiments suggest that the coniferyl moiety of imperanene is involved in the host-guest interaction.

show abstract

“…CE is often considered as the ideal technique for stereoisomer separations due to the high separation efficiency. This is also reflected in numerous review papers, for recent examples see [114][115][116][117][118][119][120]. The chiral separation mechanisms and method development strategies have also been summarized [121,122].…”

Section: Stereoisomer Analysismentioning

confidence: 97%

Recent advances in capillary electrophoretic migration techniques for pharmaceutical analysis

et al. 2014

Self Cite

View full text Add to dashboard Cite

Since the introduction about 30 years ago, CE techniques have gained a significant impact in pharmaceutical analysis. The present review covers recent advances and applications of CE for the analysis of pharmaceuticals. Both small molecules and biomolecules such as proteins are considered. The applications range from the determination of drug-related substances to the analysis of counterions and the determination of physicochemical parameters. Furthermore, general considerations of CE methods in pharmaceutical analysis are described.

show abstract

Chiral electromigration techniques in pharmaceutical and biomedical analysis

Cited by 11 publications

References 156 publications

Structural Resolution of 4-Substituted Proline Diastereomers with Ion Mobility Spectrometry via Alkali Metal Ion Cationization

Structural Resolution of 4-Substituted Proline Diastereomers with Ion Mobility Spectrometry via Alkali Metal Ion Cationization

Chiral recognition of imperanene enantiomers by various cyclodextrins: A capillary electrophoresis and NMR spectroscopy study

Recent advances in capillary electrophoretic migration techniques for pharmaceutical analysis

Contact Info

Product

Resources

About