With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Nicolai Lehnert from the University of Michigan to study how the molecule nitric oxide is broken down by bacteria. Nitric oxide (NO) is a simple but very important molecule in human physiology as it is involved in the control of blood pressure and serves as a key immune defense agent. However, some bacteria have evolved defenses against this molecule by using certain enzymes which destroy it. This project is working toward understanding the fundamental mechanism by which these enzymes are able to break down NO. The fundamental understanding of the chemistry that these bacterial enzymes catalyze is contributing to the effort to find new cures against drug resistant bacterial infections. In addition, this project is training graduate and undergraduate students in chemical synthesis, analytical characterization techniques, advanced spectroscopic methods, and how to approach and solve scientific problem). These are all valuable skills for students when they enter the job market. Finally, outreach with Cass Technical High School in Detroit is integrated in to this project by allowing underrepresented minority high school students to work in the Lehnert laboratory over the summer and obtain research experience.
This research project is aimed at using model complexes for the active site of flavodiiron nitric oxide reductases (FNORs) to map out potential chemical pathways of how NO reduction can be accomplished by non-heme diiron sites. In previous work, the Lehnert group prepared the first functional model complex, which forms the basis for the current mechanistic studies. Using spectroscopic and kinetic studies, coupled to DFT calculations, the researchers determine the molecular mechanism by which this complex catalyzes the NOR reaction. By preparing suitable derivatives of this species, they define the geometric and electronic requirements for efficient NO reduction and N2O generation by non-heme diiron active sites in general, and further explore different mechanistic possibilities. These studies ultimately identify chemically feasible pathways for NO reduction in FNORs and provide fingerprints of important intermediates of this reaction. The research group performs detailed reactivity studies on this model system in order to gain a better understanding of how non-heme (high-spin) iron(II)-nitroxyl complexes could be involved in NOR catalysis and, potentially, HNO biosynthesis.
