Abstract:

Nature has evolved metalloproteins to facilitate redox and synthetic pathways that are essential for life on Earth. Metal centers are anchored within protein scaffolds and surrounded by networks of covalent and noncovalent interactions, producing active sites that cater to each metalloprotein’s unique function. Studying these active sites and the structure-function relationships that govern them can elucidate challenging questions in synthetic transition metal chemistry. This dissertation describes the design of streptavidin-based artificial metalloproteins (ArMs) that incorporate structural components of biological dioxygen-dependent enzymes, with the goal of exploring the factors that govern dioxygen binding and reactivity. Drawing inspiration from mononuclear nonheme iron-thiolate enzymes, an ArM featuring an iron-thiolate interaction and a structurally dynamic cofactor has been synthesized and the challenges characterizing it are discussed. Additionally, interest in dinuclear oxygenases led to the synthesis of a cobalt-ArM that reacts with dioxygen to form a peroxido dicobalt species that is characterized spectroscopically. These studies contribute to the understanding of the structural factors that impact the stability of metalloprotein metal sites and their reactivity with dioxygen.