George B. Richter-Addo

Iron Mediated Chemical Biology of Nitrogen Oxides

Nature uses small molecules such as the simple nitrogen oxides (NOx) extensively in biology. For example, the simple diatomic molecule nitric oxide (NO) is a biological signaling agent for mammalian blood pressure control. NO is, however, toxic to bacteria, and nitrogen oxides such as hyponitrite are important intermediates in bacterial detoxification of NO as part of their survival. The biological chemistry of these nitrogen oxides (NOx) is directed by various iron-containing biomolecules such as the muscle protein myoglobin, the blood protein hemoglobin, and the liver protein cytochrome P450. Importantly, most of these effects depend on the biocoordination chemistry of Fe.

Our research involves determining the role that Fe plays in directing the health related chemistry of NOx species such as NO, nitrite, nitrosamines, nitrosothiols, nitrosoalkanes, and hyponitrite. These health effects range from vasodilation and neurotransmission to cancer. We utilize a range of techniques including (i) syntheses of chemical and biological intermediates, (ii) advanced electrochemistry and fiber-optic infrared and optical spectroelectrochemistry for the determination of the redox behavior of heme models, (iii) molecular biology and mutagenesis to assess the effects of active site structure on protein function, (iv) structural biology using protein crystallography to determine three-dimensional structures of biomolecules, (v) vibrational and magnetic resonance spectroscopy, and (vi) density-functional theoretical calculations to elucidate molecular and electronic structures of biological intermediates.