Mentor: Professor Sharon Burgmayer
A number of transition metals play an important role in the functioning and regulation of body processes. Almost all metals in the body are incorporated into the cofactors of enzymes where the reduction and oxidation processes at the metal centers control the behavior of the enzymes. Molybdenum, a typically neglected trace mineral is found in almost all organisms. The metal is imbedded into the cofactor of enzymes such as sulfite oxidase, xanthine oxidase, nitrate reductase in plants and bacteria, and DMSO reductase. Molybdenum enzymes are known to detoxify sulfites, a neurotoxin in the body, generate energy in the mitochondria, and regulate human growth. Molybdenum is also an important component of tooth enamel, and is suggested to play a role in the immune system and in sexual functioning of men.
All molybdenum enzymes contain a pterin ligand coordinated to the molybdenum center via a dithiolene group, more colloquially called molypdopterin (See Figure 1). Recent studies have shown that there are a family of molybdenum cofactors, nicknamed Moco. Although there has been a lot published regarding molybdenum enzymes, there has been very little reported regarding the role of the molybdopterin ligand. Our lab aims to synthesize several Moco models and test the redox capability of the models in order to better understand the redox activity of the cofactor and the role of the pterin ligand. The synthetic route consists of synthesizing the model ligand in the form of an pterinyl or quinoxalyl alkyne and the precursor molybdenum cofactor which is a tetrasulfide molybdenum complex (the pterinyl alkynes are closer in structure to molybdopterin but the quinoxalyl alkynes are easier to synthesize and therefore are used in preliminary electrochemical testing of the models). My colleague, Lauren Dillon, is preparing the pterinyl and quinoxalyl alkynes while I have been currently working on the three-step synthesis of the tetrasulfide precursor. The two molecules will be reacted to make the Moco models in the reaction depicted in Figure 2 and Figure 3. All models are characterized by NMR, FT-IR, UV-vis spectroscopy, ESI-MS and electrochemical analysis will be conducted by cyclic voltammetry.
Figure 1. Molybdopterin
Figure 2. Synthetic route to Moco quinoxaline models.
Figure 3. Synthetic route to Moco pterin models.