The molybdenum cofactor (Moco) is a remarkable metal center that lies at the catalytic heart of a variety of enzymes. The unique and `universal'Moco has the same core structure in all mononuclear molybdenum enzymes (MMEs) and is found in all forms of life. The ability of this cofactor to mediate oxygen atom transfer (OAT) and hydroxylation reactions, has given rise to the diverse family of MMEs. Similarly constituted, MMEs include dehydrogenases (e.g., formate, ethylbenzene), oxidases (e.g., sulfide, xanthine, arsenite), and reductases (e.g., nitrate, arsenate, selenate). In humans, xanthine oxidase and sulfite oxidase fulfill crucial functions in redox reactions in sulfur and purine metabolism. Microbial MMEs also indirectly impact human health through transformation of nitrate and arsenic. Defects in cofactor synthesis can result in severe physiological abnormalities leading to death. A fundamental question in biology and medicine is how has the basic unit of Moco been tuned to fulfill the various functions. The ultimate goal of our research is to better understand the reactivity of MMEs through an integrated program of inorganic, organic, physical, and reactivity studies. The broad questions that we are interested in answering are: What controls the reactivity in MMEs? How does the physical structure impose electronic structures that support the same substrate transformation with different active sites? How do these active sites influence the different phases of the catalytic cycle i.e., substrate binding, product formation, product releases and regeneration of the active site? These questions will be addressed by investigating the OAT reactivity and redox properties of molybdenum complexes and examining influence imposed by individual components of the cofactor. We will also synthesize and fully characterize oxo molybdenum complexes of dithione ligands, and investigate their properties. In addition, we conduct transmetallation reaction from copper to molybdenum, and complete the synthesis of the closest analog of pyranopterin cofactor. In accordance with the guideline of R15 program we will continue to train next generation of scientists. This proposal seeks to address fundamental questions relating to a class of enzymes that are important to human health though a hypothesis driven research.
| Ratvasky, Stephen C; Mogesa, Benjamin; van Stipdonk, Michael J et al. (2016) A mixed valence zinc dithiolene system with spectator metal and reactor ligands. Polyhedron 114:370-377 |
| Yang, Jing; Mogesa, Benjamin; Basu, Partha et al. (2016) Large Ligand Folding Distortion in an Oxomolybdenum Donor-Acceptor Complex. Inorg Chem 55:785-93 |
| Mogesa, Benjamin; Perera, Eranda; Rhoda, Hannah M et al. (2015) Solution, Solid, and Gas Phase Studies on a Nickel Dithiolene System: Spectator Metal and Reactor Ligand. Inorg Chem 54:7703-16 |
| Basu, Partha; Burgmayer, Sharon J Nieter (2015) Recent developments in the study of molybdoenzyme models. J Biol Inorg Chem 20:373-83 |
| Sparacino-Watkins, Courtney; Stolz, John F; Basu, Partha (2014) Nitrate and periplasmic nitrate reductases. Chem Soc Rev 43:676-706 |
| Pimkov, Igor V; Peterson, Antoinette; Vaccarello, David N et al. (2014) A Regioselective Synthesis of the Dephospho DIthiolene Protected Molybdopterin. RSC Adv 4:19072-19076 |
| van Stipdonk, Michael J; Basu, Partha; Dille, Sara A et al. (2014) Infrared multiple photon dissociation spectroscopy of a gas-phase oxo-molybdenum complex with 1,2-dithiolene ligands. J Phys Chem A 118:5407-18 |
| Hille, Russ; Hall, James; Basu, Partha (2014) The mononuclear molybdenum enzymes. Chem Rev 114:3963-4038 |
| Pimkov, Igor V; Nigam, Archana; Venna, Kiran et al. (2013) Dithiolopyranthione Synthesis, Spectroscopy and an Unusual Reactivity with DDQ. J Heterocycl Chem 50:879-886 |
| Deibler, Kristine; Basu, Partha (2013) Continuing issues with Lead: Recent Advances in Detection. Eur J Inorg Chem 2013:1086-1096 |
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