Chemical Reactivity and Redox Behavior of Heme-HNOx Derivatives

In this project, funded by the Chemical Structure, Dynamics, and Mechanism B Program of the Division of Chemistry, Professor George Richter-Addo of the Department of Chemistry and Biochemistry at the University of Oklahoma and Professor Michael Shaw, of the Department of Chemistry at Southern Illinois University Edwardsville will study the role of iron in the metabolism of various nitrogen oxides of relevance to the environment and human health, such as the greenhouse gas nitrous oxide and the blood pressure control agent nitric oxide. Many enzymes contain iron, and the metal plays a major role in determining how nitrogen oxides species are chemically transformed.

However, the exact role of protein-encapsulated iron in directing the mechanisms of nitrogen oxides metabolism remains relatively unexplored. This collaborative project will utilize a combination of synthesis, electrochemistry, and computational chemistry as guides for the isolation and characterization of unstable iron nitrogen oxide intermediates along biological reaction pathways, and to allow for a better understanding of the chemical role of iron in enabling the interconversions of biologically relevant nitrogen oxides.

The collaborative team combines a Ph.D. environment and a primarily undergraduate environment to provide high-level research training to a diverse group of students. Educational and outreach activities will involve the incorporation of modern electrochemistry and computational chemistry in undergraduate freshman chemistry courses, active participation in an summer program for inner city high school kids at risk for failure in academic programs, and production of online lecture educational videos in a multiplayer environment suitable for individuals with disabilities.

Nitrogen oxides (NOx) are key components of the global nitrogen cycle. Gaseous nitrous oxide is a greenhouse gas that is generated by heme proteins in fungi using a mono-Fe heme protein active site, and in bacteria using a heme/non-heme di-Fe active site. The interconversion of inorganic-NOx compounds to organo-NOx species of relevance to agriculture and biology is also mediated by some heme proteins.

In this project, the factors that lead to heme-mediated interconversions of nitric oxide (NO), nitrous oxide, nitroxyl (HNO), and (alkyl)hydroxylamines (RNHOH) will be studied. The research team will utilize a combination of synthesis, spectro-electrochemistry, and computational chemistry to determine experimental conditions that will allow for the isolation and characterization of unstable intermediates, to help elucidate the mechanisms of (i) the critical N–N bond forming step involved in NO coupling to form the greenhouse gas nitrous oxide, and (ii) the N–C bond forming steps in inorganic-NOx to organo-NOx conversions.

Particular emphasis will be placed on the role of non-metal and metal-containing Lewis acids in activating bound-NO groups towards such N–N and N–C bond-forming reactions. Extensions to other biologically relevant NOx reactions will also be made.

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.