Mentor: Dr. Sharon Burgmayer
Molybdenum is a metallic trace element and is necessary for the functioning of most living organisms. Molybdenum is found naturally in lima beans, spinach, grains, and peas. In humans, a deficiency of molybdenum can lead to health problems, since molybdenum enzymes catalyze many important processes. For example, the enzyme sulfite oxidase utilizes the molybdenum cofactor (Moco) when it transforms sulfite to sulfate via a redox reaction. Allowing the body to metabolize sulfur containing amino-acids, the failure of this reaction can cause neurological disorders. Moco is found in almost all of the molybdenum enzymes in humans is critical to biological reactions. The cofactor consists of a dithiolene organic complex coupled with a molybdenum. The chemistry of the molybdenum cofactor is unknown, and synthesizing model Moco compounds will help one understand the bioinorganic chemistry of molybdenum enzymes.
To create Moco requires the convergence of two synthetic pathways. The first is a seven-step process creating the pterinyl alkynes. The pterin is a heterocyclic compound composed of a pyrazine ring and a pyrimidine ring, containing a carbonyl oxygen and an amino group. Once the pterin is synthesized, a series of anaerobic reactions are performed to add the alkyne. The other pathway creates the tetrasulfide molybdenum complex through three steps resulting in the oxidation of molybdenum by adding sulfur ligands. The pterinyl alkyne reacts with tetrasulfide molybdenum complex resulting in the synthesis of a molybdeunum pterinyl-dithiolene complex to mimic these cofactors. These products will be characterized by FT-IR, NMR and mass spectroscopy. The goal of this research is to follow both synthetic pathways, developed by the Burgmayer laboratory, in an effort to develop the model molybdenum cofactor.