Doctor of Philosophy (PhD)
Mo and W enzymes are ubiquitous in living organisms and crucial for sustaining life. Mo and W enzyme variety is diverse, but they contain a highly conserved aspect of functionality in these enzymes, the pyranopterin-dithiolene (PDT) ligand. A total of eight possible electron redox equivalents occurs between the metal center and PDT, making the molybdenum cofactor (Moco) and the tungsten cofactor (Tuco) the most redox rich cofactors in all of biology. This research focuses on the development of new pterin-dithiolene synthetic modeling systems for Moco. The knowledge gained from the characterization of these compounds is applied to the enzymes, furthering our understanding of the role of the PDT. This work focuses on three projects, each investigating modifications on an established synthetic model complex. The first project chapter focuses on protonation of the pterin ligand and its electronic effect on the dithiolene and metal center. In the second project chapter, methylation of the pterin-dithiolene ligand induces a stable, cyclic pyranopterin and highlights the asymmetry of the dithiolene. In the last project chapter, the synthetic procedures for a novel monomeric, mono-pterin-dithiolene with a W metal center were developed and compared to the analogous Mo model complex. The projects together highlight the chemical connection between each portion of the metal-pterin-dithiolene system. A modification to one portion will also impact the others, strengthening the importance of Moco/Tuco model investigations on the entire system.
Gates, C. 2023. "The Indivisible System: Modeling The Metal-Pterin-Dithiolene System In Molybdenum And Tungsten Cofactors." PhD Diss., Bryn Mawr College.