UCLA

This dissertation describes efforts in assembling atomically precise and structurally robust hybrid nanomolecules featuring an inorganic dodecaborate cluster scaffold, as well as work in applying the functionalized nanomolecules to study multivalent interactions with proteins. Specifically, this dissertation describes two bioconjugation strategies – perfluoroaryl-thiol nucleophilic aromatic substitution (SNAr) chemistry and transition metal-mediated chemistry – for constructing well-defined and tunable cluster-based nanomolecules. Both conjugation approaches offer excellent chemoselectivity toward thiols and facilitate the rapid perfunctionalization of the cluster core with a wide scope of thiol-based molecules and macromolecules. The resulting nanomolecules exhibit high structural stability under biologically relevant conditions because of the full covalency of all the bonding interactions. Importantly, these assemblies can be rationally engineered to engender specific, multivalent recognition of a variety of protein targets with high avidity. In a biomedically relevant example, biocompatible glycosylated nanomolecules are able to inhibit the protein-protein interactions between a dendritic cell receptor and a viral envelope glycoprotein, thereby preventing the cell uptake of the glycoprotein.