UC Riverside

Self-assembled metal organic cages are supramolecular compounds with a unique internal cavity capable of creating an alternate nanophase inside of a reaction vessel (e.g. creating a hydrophilic environment inside of an organic solvent like acetonitrile). By exploiting this internal cavity, the complexes may be used for a wide array of applications in molecular recognition, small molecule transport, catalysis and even as molecular machines. Often the function of these cages becomes limited due to the flat aromatic ligands used in the assembly process. To improve the function of these cages, new methods for installing reactive groups on the interior of the cage must be explored.

This work focuses on new methods of introducing function to self-assembled cages through modifications of the ligand and cage with the goal of creating new biomimetic catalysts. These modifications can be used introduce new reactivity. By introducing native fluorescence to the chelating motif, a new class of metal selective fluorophores was discovered. While adding reactivity can be more challenging, it can be simplified to three classes: reactions that modify a preformed cage, reactions activated by the cage, and reactions hosted within the cage. Cages can be modified after their assembly through the introduction of reactive components. Internalized doubly benzylic methylene subunits can be altered post-assembly via radical promoted oxidation, with the resulting products exhibiting an impressive level of stereocontrol. The use of a strained complex enables transamination reactions to be performed at ambient temperatures giving rise to rare intermediates along the assembly pathway. A large Fe2+-iminopyridine cage bearing twelve internal carboxylic acid groups was synthesized which can affect 1000-fold rate enhancements for several reactive processes at high turnover. Further, internalization of the acid functional groups allows a tandem cage-to-cage reaction and can vary the mechanism reactions, which is unattainable by similar “free” acid catalysts. This combined process of molecular recognition and substrate activation is reminiscent of that found in the active site of enzymes. Finally, a unfunctionalized tetrahedral cage exhibiting high binding affinity, up to 200,000 M-1, was synthesized. This high binding can be used to encapsulate a catalyst to accelerate substitution reactions. This reactivity is akin to the symbiotic relationship of an apoenzyme and cofactor and is unprecedented in synthetic hosts. This is because the selective simultaneous encapsulation of multiple different guests is extremely difficult and exhibits high entropic penalties. The results of this process not only affect the reaction rate but also biased selectivity of substrates in forming quaternary complexes enabling a controlled change in the reaction mechanism.