Anna Kalinsky

Mentor: Sharon Burgmayer

Molybdenum is one of the most ubiquitous inorganic elements in biology. Molybdenum-containing enzymatic cofactors (MoCo) are evolutionarily ancient and found in virtually every living organism. MoCo is primarily a redox cofactor, and has important implications not only for the biological fixing of elements such as carbon, nitrogen, and sulfur, but also an important role in global geochemical cycles. Indeed, mutations which obstruct the biosynthesis of MoCo are mutations which are incompatible with life – human molybdenum cofactor deficiency leads to death within a few days of birth due to buildup of sulfate in the neurological system.

Despite its chemical importance and medical significance, the specific chemistry of the cofactor is still a murky realm. MoCo has numerous structures depending on the specific enzyme, but all structures have several things in common: the molybdenum center itself, at least one molybdenum-coordinating oxo group, and a bidentate ligand consisting of a dithiolene and a tricyclic pyranopterin. To date, the Burgmayer group has synthesized the only molybdenum cofactor model system in the literature consisting of an oxygen-coordinated molybdenum and a pyranopterin dithiolene system. Prior research has demonstrated numerous surprising properties of this system. While the molybdenum center is capable of one-electron redox activities from the +4 to +6 oxidation states, the pterin has demonstrated itself to be a non-innocent ligand capable of participating in two-electron, two-proton redox processes. The pyran ring also shows reversible ring-cleavage.

It is notable that all of these processes were done using studies on the partly-oxidized “dihydro” pterin system. My research this summer will continue my investigation into the synthesis and properties of the more biologically relevant, fully-reduced “tetrahydro” pterin ligand species. Past research on this species has proven difficult mainly due to the instability of the compound, both in air and in exposure to reducing agents in solution. This has been remedied by performing the necessary syntheses and analysis in inert dinitrogen atmosphere, but even so, a stable solid product of high purity has yet to be isolated. This summer I will continue further analysis into the reaction in situ, as well as study its structure and reactivity by various techniques, including 1H NMR, UV/Vis spectroscopy, and computational methods. I will also continue investigations into earlier synthetic processes, such as the phosphine-mediated conversion of Mo-sulfido to Mo-oxo, which proceeds by an unknown mechanism.