Salient Features of Enantioselective Gas Chromatography: The Enantiomeric Differentiation of Chiral Inhalation Anesthetics as a Representative Methodological Case in Point

Abstract

The enantiomeric differentiation of the volatile chiral inhalation anesthetics enflurane, isoflurane, and desflurane by analytical and preparative gas chromatography on various modified cyclodextrins is described. Very large enantioseparation factors α are obtained on the chiral selector octakis(3-O-butanoyl-2,6-di-O-pentyl)-γ-cyclodextrin (Lipodex E). The gas-chromatographically observed enantioselectivities are corroborated by NMR-spectroscopy using Lipodex E as chiral solvating agent and by various sensor devices using Lipodex E as sensitive chiral coating layer. The assignment of the absolute configuration of desflurane is clarified. Methods are described for the determination of the enantiomeric distribution of chiral inhalation anesthetics during narcosis in clinical trials. The quantitation of enantiomers in a sample by the method of enantiomeric labeling is outlined. Reliable thermodynamic parameters of enantioselectivity are determined by using the retention-increment R' approach for the enantiomeric differentiation of various chiral halocarbon selectands on diluted cyclodextrin selectors.

Synergistic Effects of Trace Amounts of Water in the Enantiodiscrimination Processes by Lipodex E: A Spectroscopic and Computational Investigation

“…Among them the most popular are chromatographic [1][2][3][4][5][6] and spectroscopic methods, and, particularly, nuclear magnetic resonance (NMR). This issue has impacted various research areas specially dedicated to the development of methods for the analytical separation of mixtures of enantiomers.…”

“…This issue has impacted various research areas specially dedicated to the development of methods for the analytical separation of mixtures of enantiomers. Among them the most popular are chromatographic [1][2][3][4][5][6] and spectroscopic methods, and, particularly, nuclear magnetic resonance (NMR). [6][7][8][9][10] The easy commercial accessibility of chiral stationary phases for high-performance liquid chromatography / gas chromatography (HPLC/GC) and of chiral auxiliaries for NMR spectroscopy has made these analytical methods very popular and has led to the recognition, especially in chromatography, of the critical dependence of the reproducibility of analytical separations from the presence of intentional additives or unintentional impurities.…”

Silylated-Acetylated Cyclodextrins as Chiral Sensors for the Enantiodiscrimination of Fluorinated Anesthetics

“…Among different cyclodextrin derivatives, lipophilic ones have led to the design of promising analytical and preparative chromatographic separation systems in apolar media based on chemo- and stereoselective molecular recognition [ 14 , 15 , 16 , 17 , 18 , 19 ]. In addition, among lipophilic derivatives, (2,3-di- O -acetyl-6- O - tert -butyldimethylsilyl)cyclodextrins (AcSiCDs, Figure 1 ) have been tested as CSAs for NMR spectroscopy [ 20 , 21 ], and, more recently, comparisons have been made of the enantiodifferentiation of substrates that are endowed and devoid of fluorine atoms, specifically 1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane (COMP B in Figure 1 ) and methyl 2-chloropropionate [ 22 ].…”

“…The origin of chiral discrimination processes was investigated thoroughly from a stereochemical point of view by detecting the intermolecular dipolar interactions via ROESY (Rotating-frame Overhauser Enhancement SpectroscopY) experiments [ 26 , 27 ]. Deuterated cyclohexane (C 6 D 12 ), which had already been exploited as a solvent in the analysis of chiral discrimination phenomena generated by AcSiCDs [ 22 ], was selected for this NMR study, considering that it could potentially favor the host/guest interactions and that it effectively mimics the apolar gas chromatographic environment [ 14 , 15 , 16 , 17 , 18 , 19 ].…”

Heteromerous Bistricyclic Aromatic Enes: Dynamic Stereochemistry of Xanthylidene‐Anthrones

“…Dynamic chromatography can be successfully employed to determine enantiomerization and diastereomerization barriers by peak shape analysis of dynamic elution profiles . Enantioselective gas chromatography and high‐performance liquid chromatography (HPLC) are widely used techniques for the investigation of interconversions of enantiomers and their separation.…”