Redox Behavior and Chemical Reactivity of Heme-HNOx Complexes

University Of Oklahoma Norman Campus, Norman OK

Investigators

Abstract

The Chemical Structure, Dynamics & Mechanisms B Program of the Chemistry Division at the NSF supports the collaborative research between Professor George B. Richter-Addo at the University of Oklahoma (OU) and Professor Michael J. Shaw at Southern Illinois University Edwardsville (SIUE). The overall goal of this research is to prepare and characterize reactive biological intermediates of relevance to the global nitrogen cycle and human health. Emphasis is placed on the fundamental iron-mediated chemistry of the nitrogen oxides (NOx) that have been implicated in various processes such as atmospheric pollution, blood pressure control in humans, and in bacterial survival or death. Although the simplest NOx species, namely nitric oxide (NO) is known to regulate normal blood pressure, not much is known about the generation and action of related species such as nitroxyl (HNO) and nitrosoalkanes (RNO). This collaborative group has joint expertise in chemical synthesis and electroanalytical chemistry, and combines a Ph.D. environment (at OU) and a primarily undergraduate environment (at SIUE) to provide high-level training to a diverse group of students. Outreach activities involving inner-city high school students from low-income and disadvantaged backgrounds are an essential component of this project. Heme-HNO and -hyponitrite compounds are important intermediates in the biological pathways of the overall global nitrogen cycle. For example, bacteria convert the diatomic vasodilator molecule NO to nitrous oxide via a hyponitrite intermediate using a di-iron active site, whereas fungi perform a similar NO-to-nitrous oxide reaction using a mono-iron active site. The fungal reaction involves initial hydride attack at a ferric heme nitrosyl to generate a heme-HNO intermediate. This research team recently succeeded in generating a synthetic model system to demonstrate heme-HNO formation via hydride attack on a ferric heme nitrosyl, which provided an appropriate framework to determine factors that promote further reactions of these heme-HNO species. In this project, the aims are to: (i) prepare a representative range of ferric heme nitrosyls, (ii) explore reactions involving nucleophilic attack at the bound nitrosyls to generate heme-XNO derivatives (X = H, alkyl/aryl), (iii) determine the redox behavior of these species especially those involving proton-coupled electron transfers, (iv) prepare heme model-hyponitrite compounds and establish their reactivity patterns, and (v) prepare the related heme model-NONOate derivatives to determine the factors that promote decomposition of these species to generate the vasodilator NO molecule.