CAREER: Understanding the Role of Nickel-Sulfur Complexes in Catalytic ROS Detoxification: Insight From Ni-SOD Synthetic Analogues

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The Chemical Catalysis Program supports Professor Todd C. Harrop at the University of Georgia for a research project that will advance our understanding of the chemistry of biologically relevant metal-sulfur coordination units in their catalytic role as scavengers of reactive oxygen species (ROS) in metalloenzymes. Current knowledge in this area stipulates that such coordination units should be prone to ligand-based oxidation instead of primarily metal-centered redox. Thus, to understand the fundamental chemical properties of these systems, Professor Harrop will initiate a synthetic bioinorganic-modeling approach towards the newest and most unusual superoxide-detoxifying enzyme namely, nickel superoxide dismutase (Ni-SOD). To address the role of biological coordination, the PI will synthesize and characterize a range of Ni-N/S complexes that are direct electronic and structural mimics of Ni-SOD. The fundamental reaction chemistry of Ni with ROS, in particular Ni-S and Ni(III) complexes, is poorly defined and relatively unexplored. Thus, the reactions of these complexes with ROS like superoxide, H2O2, and NO will be performed. These reactivity studies will be monitored by a variety of spectroscopic and computational methods that will define discreetly for the first time these biologically important interactions. Collectively, the contribution of these studies will allow the understanding of new concepts in the unique coordination and reaction chemistry of Ni-SOD and result in the intelligent design of molecules with SOD activity for use in catalysis and pharmaceuticals, thus contributing to a significant stream of research.With the support of the Chemical Catalysis Program in the Chemistry Division at the National Science Foundation, Dr. Harrop will provide biochemists and theoreticians with spectroscopic, structural, and reactive benchmarks of potential species that are important to understanding the Ni-SOD catalytic pathway. This work will also have a broader impact on science education through a variety of synergistic activities. The principal goal of these integrated educational activities is to increase awareness, participation, and retention of underrepresented minority groups in the STEM disciplines, specifically African-Americans in chemistry. These efforts involve a new research-partnership initiative that the PI will establish with Fort Valley State University (FVSU), a public HBCU in the state of Georgia. A summer research internship will be awarded annually throughout the grant period to an undergraduate chemistry major from FVSU to be conducted in the PI's lab on Ni-SOD analogues. The award will establish a new link with an HBCU in the state and will lead to a strong and continual pipeline of FVSU students pursuing advance degrees in chemistry and hopefully at UGA. This award will support salary for the undergraduate summer researcher and for their travel to conferences, better preparing these young scientists for careers in chemical research.