Solvent Effects and Internal Functions Control Molecular Recognition of Neutral Substrates in Functionalized Self-Assembled Cages

<b>A</b> suite of internally functionalized Fe₄L₆ cage complexes has been synthesized with lipophilic end groups to allow dissolution in varied solvent mixtures, and the scope of their molecular recognition of a series of neutral, nonpolar guests has been analyzed. The lipophilic end groups confer cage solubility in solvents with a wide range of polarities, from hexafluoroisopropanol (HFIP) to tetrahydrofuran, and the hosts show micromolar affinities for neutral guests, despite having no flat panels enclosing the cavity. These hosts allow interrogation of the effects of an internal functional group on guest binding properties, as well as solvent-based driving forces for recognition. Introducing polar effects to the interior of the cavity enhances guest binding affinity in nonpolar solvents; adding space-filling aliphatic groups reduces affinity in all cases. While high dielectric solvents such as acetonitrile strongly favor guest binding, "low dielectric, high polarity" solvents such as HFIP strongly occupy the cavity and prevent guest recognition. Analysis of the cage optical transitions shows that the guests interact with the central ligand cores and reside in close proximity to the internal functions. These results have implications for supramolecular catalysis: balancing directed host:guest interactions (e.g., H-bonds) with entropic effects from solvent displacement is essential for reactions in these (and related) biomimetic hosts.