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Nanomedical approaches are of great interest due to their potential for specifically delivering packaged contrast agents and drugs to sites of disease while avoiding healthy tissue. Non-mammalian viruses, which are noninfectious to humans, can be used as unique nanoscale scaffolds with many advantages for nanotechnology and biomedicine. Compared to synthetically programmed materials, these particles can be precisely arranged into a diverse array of shapes and sizes, and there are many available avenues for easy and reproducible modification. Here, I investigated the expansion of the potential of these viruses for diverse applications in nanomedicine. First, I demonstrated the capability for interior engineering of a well-known icosahedral plant virus, cowpea mosaic virus (CPMV), for the encapsulation of a range of molecules, including fluorophores to enable optical imaging in the setting of cancer detection and diagnosis. Then, some design considerations were examined for the use of nanoparticles for fluorescence imaging, which informed our choices for subsequent studies. Dye density, dye localization, conjugation method, and cell uptake were all found to affect the resultant fluorescence intensity with the optimal design parameters being: non-aromatic linker chemistries, exterior particle conjugation, and dye spacing of around 8-10 nm. A second set of studies explored drug delivery using virus-based particles, demonstrating their utility for photodynamic therapy through solubilization of highly hydrophobic photosensitizers as well as for the treatment of chronic infections through using their native tropism. Finally, as increasing evidence suggest that shape is an important parameter for cell and tissue interactions, we explored the effect of aspect ratio and shape in mediating cell uptake and targeting the vessel wall. Nanoparticle chains were created, with clear differences seen in cell uptake due to shape-based as well as avidity effects. Additionally, in a parallel investigation, rod-shaped particles were shown to be better able to marginate to the side of the vasculature and bind to sites of thrombosis. For more specific thrombus targeting, peptides with affinity for a mediator of thrombosis were identified and investigated for their potential to enhance particle binding to thrombi. Overall, my research spanned the imaging and treatment of cancer, infectious disease, and cardiovascular disease and added to the possibilities of using virus-based particles for future biomedical applications.

The synthesis, study and catalytic properties of chiral terminated dendrons based on an intramolecularly folded pyridine-2,6-dicarboxamide branch unit is reported. Two differently terminated chiral dendrons were prepared and studied for their chiroptical properties: 1.) N(π)-methyl histidine dendrons were prepared and tested as organocata-lysts in the kinetic resolution of secondary alcohols and an intramolecular acyl rear-rangement of oxindoles to generate all carbon, quaternary stereocenters, and 2.) bi-phenyl and tetra-phenyl-core-based, chiral terminated dendrons were synthesized and tested for their catalytic properties in the titanium mediated, asymmetric addition of allyl-tributyltin to aldehydes. In the former project (organocatalysis), the dendrons were, after much synthetic difficulty, synthesized up to their second generation and exhibited a slightly positive dendrimer effect from G0 to their second generation hierarchy. Using circular dichroism (CD) spectroscopy, the dendrons exhibited a positive Cotton-effect (CE) (P-helical bias) that was enhanced not only from the first to second generation, but also from organic to aqueous solvents. In the latter project (asymmetric allylation of al¬dehydes), various amide termini bi/tetra-phenyl core-based dendrons were prepared and showed a cooperative effect (in terms of enantioselectivity) when the tetraphenyl core was used. CD studies showed that the dendrons, when attached to the aforementioned cores, developed a bias toward an M-helical sense, which was much more pronounced in the tetraphenyl dendron.

Part 1: Synthesis and Study of Liquid Crystalline Dendrimers as Additives to Dental Composites. A series of intramolecularly hydrogen-bonded dendrimers based on pyridine-2,6-dicarboxylate branching units and a 1,3,5-benzenetricarboxylic acid core are described. Three series of dendrimers were synthesized differing in the terminal group linkage as well as the group chain length. Two of the dendrimers' termini are linked via amides with chain lengths of five or six carbons. The third dendrimer's termini is attached via an ester linkage with a 12-carbon chain length. The dodecyl-terminated dendrimer was shown by optical microscopy to exhibit liquid crystalline phases, however, these phases could not be unambiguously identified. Polymerizable methacrylate groups were attached to the dendrimer termini and the dendrimer was incorporated into a bisEMA/HDMA based filled dental composite. DSC data indicates a decrease in the degree of polymerization with increasing dendrimer concentration. Flexural strength data also indicates a weakening of the polymerized composite with increasing dendrimer concentration. However, at higher dendrimer concentrations, the flexural strength is unusually high when the extremely low degree of polymerization is considered. Part 2: Effect of Selective Metal Coordination on Dendrimer Structure. Investigation was undertaken into end group cooperativity in dendrons and dendrimers with chiral oxazoline based termini. In the course of this research, a 4-aminopyridine(bis)oxazoline displaying a noncentrosymmetric crystal structure was synthesized, along with a novel, helically biased pyridine(bis)amido(bis)oxazoline based series of dendrons and their metal complexes. Barriers to helical interconversion were obtained via NMR line shape analysis for the first generation dendron in THF and its zinc complex in several solvents. Circular dichroism (CD) data indicates the presence of a highly biased solvent and temperature independent P-helix. This conformation was also observed in the solid state via crystallographic analysis. Copper and nickel complexes of the first generation dendron were also synthesized. CD data and crystallographic results also confirm the presence of the P-helix. A first genreration dendrimer as well as dendrons up through the third generation were synthesized along with their corresponding copper and nickel complexes.