Stereodiscrimination of guests in chiral organosilica aerogels studied by ESR spectroscopy

Macroporous materials containing surfaces with chiral groups are highly relevant for applications in the chromatographic separation of enantiomers. Despite these materials being highly engineered and commercially available, optimization was often done empirically. A rational design of future and improved solid phases for chiral chromatography requires that one understands how the chemical structure of a surface influences the stereoselectivity of the enantiomers at the surface. Despite the difference in the interaction enthalpies being only in the 1–2 kJ·mol ⁻¹ range, an ideal surface would exclusively interact with one enantiomer. However, the question of which selectivity is sufficient or necessary to reach separation is an important point. We have employed the two enantiomers of a chiral, nitroxide-based spin probe as guests in organo-modified macroporous host materials and applied ESR spectroscopy as a tool to investigate their rotational mobility. Using a well-established and commercially available material confirmed the method’s reliability. The data underline how crucial the choice of the right solvent is if one wants to reach sufficient selectivity. Together with a series of custom-made organosilica aerogels, it is shown that adjusting solvent and surface properties so that the two enantiomers (+) and (−) experience a different chemical environment is key. Otherwise, there might be a dynamic equilibrium between surface-adsorbed and mobile spin probes without stereodifferentiation. With this knowledge, it was possible to reach higher selectivity values than for the commercial material. A particularly interesting result was that better performance could be achieved if one attaches bulky, hydrophobic groups directly to the stereocenter. The effect of such neighboring groups on the enantioselectivity highly depends on the distance they have to the stereocenter.