Design, Synthesis, and Evaluation of Coordination Complexes for Diagnostic and Therapeutic Applications

A primary goal of medicinal inorganic chemistry is the development of coordination complexes as diagnostic and therapeutic agents. This thesis describes three projects that fall under the scope of this goal. Two projects focus on the development of Gd(III)-chelates as imaging probes for magnetic resonance imaging (MRI). The first describes the structural optimization and mechanistic investigation of a Zn(II)-responsive MR contrast agent. It was determined that altering the distance between the Gd(III) chelate and the Zn(II)-binding domain dramatically effects the efficacy of these probes. Further mechanistic studies provided a deeper understanding of the structure-function relationships that determine this trend, allowing us to elucidate a set of design rules for the development and improvement of similar bio-activated contrast agents. The second project describes the development of a bacteria-targeted MR probe that can be used for non-invasive, in vivo detection of infection. The final project describes the use of computational chemistry, specifically density functional theory (DFT), to understand the kinetic and thermodynamic parameters that control the axial ligand lability of cobalt Schiff base complexes, such as [Co(acacen)Im2]+, which can be used as inhibitors of protein activity.