Research Mentor: Sharon Burgmayer, Chemistry
My research deals with the molybdenum cofactor (moco), a complex containing the element molybdenum which is present in enzymes in all life forms. Moco is necessary for the function of many enzymes which are involved in redox, such as aldehyde oxidase. The cofactor, in fact, is necessary for human life: humans born without it will die shortly after birth. Structurally, it consists of a molybdenum oxide bound to molybdopterin, which is a heterotricyclic molecule containing a pyran dithiolene bound to a pterin ring. Despite being so prolific, relatively little is known about the detail of the redox behaviors of the molybdenum cofactor.
My research is part of a greater project to both synthesize the cofactor from scratch and to examine its properties using a model structure. The cofactor has been isolated from enzymes, but synthesizing from scratch numerous advantages. It theoretically allows for greater yield of moco. Additionally, we can use different ligands on our moco model to view how modifications to the cofactor can affect its properties. The goal of my research is to analyze the redox properties of our moco model and to work towards a better and more efficient synthesis of the moco model as well as towards the synthesis of the molybdenum cofactor.
There are two synthetic pathways which must converge in order to make our moco model. I have been working on the “tetrasulfide” pathway, which involves the synthesis of the part of the figure on right in black, with the addition of a bidentate four-sulfur ring ligand on the central molybdenum. While I do the reaction which joins the tetrasulfide reagent with the pterin ligand BMOPP, highlighted in blue, I have never synthesized BMOPP, nor any of its precursors. This summer I will begin learning about the pterin synthetic pathway. I will also be working to refine the synthetic pathway which changes the double-bound sulfur molecule on the molybdenum to a double-bound oxygen. For this pathway, we have switched from using triphenylphosphine, an inexpensive solid, to using triethylphosphine, a more dangerous and expensive reagent which is much easier to remove from the final product without contamination and which greatly speeds the rate of the reaction. I will be working to optimize the triethylphosphine reaction.
I will also be doing some research into a variation of the Tp* ligand synthesized by Dr. Elizabeth Papish at Drexel University, called TtzR,Me. The Tp* portion of our moco model stabilizes the model, much as the molybdenum cofactor is stabilized by its enzyme. Using a different ligand could change the stability of our model.