Chemical Reactivity of Metalloporphyrin Nitrosyls and Related Compounds

In this project, Professor George Richter-Addo and his research group in the Department of Chemistry and Biochemistry at the University of Oklahoma are investigating factors that promote the formation of carbon-nitrogen bonds mediated by heme/metalloporphyrin centers. Iron-carbon bonds are known to exist in some heme protein derivatives in mammals, and the small molecule nitric oxide (NO) is a well-known biological signaling agent. The goal of this research project is to determine the structural and electronic framework that will promote the insertion of NO into the metal-carbon bonds of heme protein model compounds to form new carbon-nitrogen moieties of biological and synthetic relevance. The experiments will be complemented by theoretical calculations through collaborations to unravel the mechanisms of the observed reaction pathways. The project lies at the interface of inorganic, organometallic, and computational chemistry, and will provide excellent educational and research training to graduate and undergraduate students and postdoctoral fellows in preparation for careers in academia, industry, or national laboratories. The main objective of this project is to determine the conditions that will lead to insertion of the small molecule NO into metalloporphyrin-carbon bonds for the group 8 and 9 transition metals. The project focuses on the first and second row metals, the former for their biological relevance, and the latter for the potential applications in non-biological chemistry. A combination of synthesis/reactivity and density functional theoretical calculations will be employed. Two approaches are adopted in this project. First, insertions of NO into the metal-carbon bonds of synthetic metalloporphyrins will be probed in solution and through crystal-gas reactions and monitored by spectroscopy. The expected heme–RNO products will also be isolated from solution and characterized by spectroscopy and X-ray crystallography; the nature of RNO binding (N- or O-bound) will be determined, as will their kinetic and thermodynamic stabilities. Second, a complementary approach to this research involves determining the conditions that will promote attack of carbon-based nucleophiles at electrophilic metal–NO centers in heme protein models. The results of this project are expected to establish fundamental baseline knowledge regarding which (porphyrin)metal(alkyl/aryl) systems are prone to NO insertions, thereby significantly advancing our understanding of heme-enabled NO reaction chemistry of relevance to biology. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.