Mentors: Dr. Sharon J. Nieter Burgmayer and Graduate Student Kelly Ginnion
The second row transition metal molybdenum, atomic number 42, is a naturally occurring element in a countless number of biological reactions. Assuming the role as a biological catalytic center, molybdenum occupies the catalytic site in more than forty essential enzymes, which control the oxidation-reduction reactions for a broad range of inorganic and organic substrates. Considering the ubiquitous nature of molybdenum enzymes, with its presence in everything from simple bacteria to human beings, it is no wonder that the element has a profound evolutionary history, contributing significantly to the biological function of virtually every living organism. From the human perspective alone, three molybdoenzymes—sulfite oxidase, xanthine oxidase and aldehyde oxidase—are essential for proper health.
Contrary to popular scientific belief, molybdenum has not survived the perils of evolution single-handedly but rather it is now believed that such enzymes are the chemical descendants of tungsten enzymes, whose origin was traced to the most ancient of organisms, archaebacteria. Consequently, it has been found that the structures and functions of tungsten enzymes in bacteria are similar to those of the molybdenum enzymes typically found in more complex species like human beings. Molybdenum and tungsten enzymes are the only biological molecules to utilize the dithiolene as a metal ligand. Together, the dithiolene ligand bound to the molybdenum center in all molybdenum enzymes has been identified by the name of the molybdenum cofactor (colloquially referred to as Moco) illustrated in figure 1 below.
Figure 1. Moco consists of a pterin structure (blue) fused to a pyran (red) ring bearing an exocyclic dithiolene group (green) that is the site of metal coordination.
The identity of the molybdenum cofactor, the catalytic site in pyranopterin molybdenum enzymes, was sought through studies of the molybdenum enzymes and through synthetic efforts to assemble compounds that reproduce key spectroscopic, structural, and reactivity properties of the catalytic Mo center. The Burgmayer laboratory has developed novel models for the molybdenum cofactor which incorporate key structural features in all Mo and W enzymes including a dithiolene chelate joined to a pterin. The goal of this summer laboratory experience will be to synthesize the precursors of Moco models and then to utilize the starting material in order to build the pterin-dithiolene ligand. Generally, the synthetic scheme will entail coupling a Mo-tetrasulfide complex with a pterinyl alkyne to produce [Tp*Mo(O/S)(pterin-dithiolene)] complexes in both Mo (4+) and Mo (5+) oxidation states. While previous work has focused on the characterization on the purified Mo (5+) species, there is a strong hope of exploring the fascinating redox chemistry associated with Mo (4+) in the near future