Structural and thermodynamic investigations of an unusual enantiomeric separation: Lipodex E and compound B

Abstract

Compound B (1,1,3,3,3-pentafluoro-2-fluoromethoxy-1-methoxypropane) can be separated by gas chromatography with an extraordinary chiral separation factor on a column coated with Lipodex E (octakis(3- O-butanoyl-2,6-di- O- n-pentyl)-γ-cyclodextrin). The enantioselectivity is greatly reduced when employing the β-cyclodextrin analogue. To further investigate the background of this unusual separation, the complexation between ‘compound B’ and Lipodex E (octakis(3- O-butanoyl-2,6-di- O- n-pentyl)-γ-cyclodextrin) and heptakis(3- O-butanoyl-2,6-di- O- n-pentyl)-β-cyclodextrin were studied by NMR. Association constants of the interaction of the two enantiomers of compound B with Lipodex E and its β-cyclodextrin analogue were determined by NMR chemical shift titration and showed a large difference corroborating earlier GC results. Heteronuclear NOE measurements proved that inclusion complex formation is taking place with compound B situated inside the cavity of the cyclodextrin moiety. Differences between the inclusion complex structures and their connection to association constants are discussed.