Introducing Hydrofluoroethers as Modifiers for Enantioseparation in Super/Subcritical Fluid Chromatography

The addition of modifiers led to a marked expansion of the chemical space that can be analyzed with super/subcritical fluid chromatography. The introduction of new modifiers can help tune selectivity with commercially available stationary phases. This work presents an entirely new class of modifiers, which offers unique selectivity not afforded by conventional solvents. We utilize hydrofluoroethers, commonly designated as Engineered Fluids, as modifier for enantioseparations on polysaccharide-based chiral stationary phases under super/subcritical fluid chromatographic conditions. Engineered fluids have been commonly utilized as heat transfer liquids for replacing chlorofluorocarbons. In this study, we utilize three different hydrofluoroethers, namely, Novec 7000, 7100, and 7200, to obtain novel selectivity on Chiralpak AD and IG columns as proof of concept for their utility. This study highlights the enhanced retention and selectivity changes afforded by these solvents, when blended with methanol in comparison to neat methanol, which is the most commonly used modifier. The effects of using different blend concentrations have also been elucidated in this study, with findings suggesting the importance of optimizing the amount of Engineered Fluid in the bulk mobile phase. The manuscript also dives into the variation in selectivity, when different hydrofluoroethers are used in the blend, pointing to the utility of each of the tested solvents.