Extraordinary chiral discrimination in inclusion gas chromatography. Thermodynamics of enantioselectivity between a racemic perfluorodiether and a modified γ-cyclodextrin

The enantiomers of the perfluorodiether “compound B” [2-(fluoromethoxy)-3-methoxy-1,1,1,3,3-pentafluoropropane], a decomposition product of the inhalational anesthetic sevoflurane [2-(fluoromethoxy)-1,1,1,3,3,3-hexafluoropropane], were separated by gas chromatography on octakis(3-O-butanoyl-2,6-di-O-n-pentyl)-γ-cyclodextrin (Lipodex E), dissolved in polysiloxane PS 255 (30% w/w), with an unexpectedly high separation factor of α=10.6 at 26 °C. Using the concept of the retention increment R′, non-enantioselective and enantioselective contributions to retention were separated and thus reliable thermodynamic parameters of enantioselectivity, i.e. −ΔS,R(ΔG)=5.7 (0.05) kJ/mol at 303 K, −ΔS,R(ΔH)=20.1 (0.64) kJ/mol, ΔS,R(ΔS)=−47.4 (2.0) J/K mol and Tisoenant=424 (30) K or ∼150 °C, were determined by temperature-dependent measurements. The enantiomeric bias represents the largest values ever measured in enantioselective gas chromatography. An equation is presented which allows calculation of the non-enantioselective contributions to retention from measurements at two arbitrary concentrations of Lipodex E in polysiloxane. Surprisingly, the enantioselectivity is greatly reduced when employing the β-cyclodextrin analogue and breaks down completely with the α-cyclodextrin analogue of Lipodex E.