Access Type

Open Access Dissertation

Date of Award

January 2013

Degree Type


Degree Name




First Advisor

Jeremy J. Kodanko


Two separate subjects are described in this dissertation. The first part describes novel methodologies for attaching polypyridyl ligands into unnatural amino acids. The first chapter describes the different possibilities for attaching metal ligands to peptides and their applications as potential imaging and therapeutic agents covered so far in the literature. It is followed in the second chapter by the description of a new method for the construction of metal-peptide conjugates through the use of three unnatural amino acids, and their adaptation to solid phase synthesis. The third chapter describes the synthesis of a novel, "optimal" substrate for the enantioselective alkylation reaction of benzophenone glycine imine derivatives. Optimization of the enantiomeric excess, scope and compatibility with acid-labile containing protecting groups are disclosed.

The second chapter presents the synthesis of the first caged cysteine protease inhibitor. After an introductory survey of different Ru and Pt complexes used as potential therapeutic cancer agents, cysteine protease inhibitors are described. The syntheses of RuII(bpy)2 complexes caging cathepsin inhibitors are revealed with full characterization in the following chapters. The stability of the complexes in the dark in aqueous solutions and their ability to release the inhibitors upon irradiation with visible light are shown, followed by cathepsin activity inhibition studies, in vitro and in cellulo. Finally, the toxicity of the complexes is evaluated in cell viability studies.

Included in

Chemistry Commons