UC Riverside

Enzymes are catalysts found in nature that show high rate accelerations and substrate selectivity compared to synthetic catalysts. The high selectivity of enzymes derives from their active sites. These sites contain functional groups that allow enzymes to bind to substrates of specific shapes and sizes. The high efficiency and selectivity shown by enzymes has prompted chemists to mimic their behavior in a more easily analyzable system. This has led to the creation of synthetic molecules known as self-assembled metal-ligand cages. However, most cages are featureless, and lack the functional groups found in enzymes needed for binding and catalyzing reactions. My research is, therefore, geared towards overcoming the inherent problems faced when modifying these cage molecules with reactive functions. Past studies have shown that twelve internal acid groups can be incorporated in the active site of a cage complex. My research has investigated the factors that affect the reactivity of the acid cage. The reactivity is controlled by both the nature of the nucleophile and size and orientation of the electrophile when bound. Electrophiles that have more bulk around the basic oxygen are activated less effectively, due to being located further away from the cage’s acid groups. Smaller electrophiles show minimal size-selectivity and react at a slower rate. While spherical guests are highly dependent on substitution, flat guests are unaffected by both size and shape differences in the cage. Further research has shown that the acid cage can activate complex, multistep reaction pathway. This is challenging because most reactions performed with artificial enzymes are relatively simple one or two step processes. Results from this study reveal differences in reactivity based on the size and fitting of the intermediate molecule formed inside the cage. Enzymes can also employ “cofactors.” By adding a small molecule acid to an unfunctionalized version of the acid cage, this allows size-selective, acid-catalyzed substitution reactions to occur with faster rates and variable mechanisms than simply with the acid alone. Finally, my research has formed a cage with twelve internal amine groups inside its cavity. The amine functional groups are protonated due to the water created during the assembly process. The internal amines are less basic than normal, when compared to a molecule in free solution. Similar to an enzyme’s ability to control both acidity and basicity of its side-chain in its active sites, this complex can exhibit the same type of control using its internal amines and the cationic superstructure.