Investigating the Dioxygen Activation Mechanisms of Biologically Relevant Nonheme Iron Complexes

Bacteria employ a wide variety of iron-containing enzymes to breakdown natural and human-generated compounds in the environment. Such reactions commonly proceed by cleaving the carbon-carbon bonds of the molecules in a process that requires dioxygen (O2) from the atmosphere. The mechanism by which biological iron sites facilitate these O2-dependent reactions is not fully understood, which hinders the design of man-made molecules capable of using O2 as a cheap and environmentally-friendly oxidant. In this project, Dr. Adam Fiedler is generating a series of model systems, ranging from small complexes to supramolecular assemblies, to obtain molecular-level insights into the O2 reactivity of iron in both biological and man-made contexts. A powerful combination of spectroscopic and computational tools is utilized to characterize unstable and transient species that have been proposed (but rarely observed) in Nature. In this way, the project provides a more complete picture of reactions that are essential for the remediation of polluted soils and groundwaters. The interdisciplinary nature of the project offers a valuable training experience in both experimental and theoretical methods for graduate and undergraduate students. Dr. Adam Fiedler collaborates with local teachers to engage high-school students in activities that combine chemistry with artistic expression. This outreach program exposes students to concepts and instrumentation used in the project, thereby increasing scientific literacy and the chances that students pursue college degrees in science. <br/><br/>With funding from the CSDM-B Program of the Chemistry Division, Dr. Adam Fiedler of Marquette University is developing synthetic iron-containing complexes that mimic key features of nonheme iron dioxygenases. Dioxygenases that cleave carbon-carbon bonds are critical for the microbial degradation and assimilation of organic compounds that arise from both natural and human sources. However, the O2 activation mechanisms employed by these enzymes are not fully understood. In particular, there is uncertainty regarding the geometric and electronic factors that govern the reactivity of pivotal intermediates featuring superoxo, peroxo, and/or substrate radical ligands. This project combines coordination chemistry, reaction kinetics, spectroscopic techniques, and computational methods to illuminate the complex relationships between structure and reactivity in bio-inspired iron complexes, including transient intermediates of catalytic significance. In addition, new approaches for incorporating well-defined second- and third-sphere ligand architectures are developed. These efforts provide fundamental knowledge regarding O2 activation processes in a variety of metalloenzymes and aid in the design of new oxidation catalysts. The methods used in this research offer interdisciplinary training for undergraduate and graduate-level scientists. Dr. Adam Fiedler is also engaged in outreach activities directed towards high-school students that stimulate interest in science by emphasizing the visually appealing aspects of inorganic chemistry and crystallography.<br/><br/>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.