Applying Rules of Life to Catalysis: Significance of Distorted Coordination Environments in Enzyme Active Sites

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Nature accomplishes challenging reactions under ambient conditions using as catalysts enzymes that contain one or more Earth-abundant metals. The coordination environment of the metal ions situated in these enzymes' active sites are often an inspiration for new synthetic catalysts. However, there is often a significant difference between the reactivity of enzymes and their synthetic analogs, which reveals the existence of subtle rules that govern the reactivity of the metal ions in living systems. With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Shiyu Zhang from The Ohio State University to discover, elucidate, and apply fundamental rules that enzymes active sites employ to achieve difficult cellular reactions. The research project is integrated with an educational program whose goal is to teach students how to engage members of the community in modern STEM research and to improve scientific literacy through collaborative outreach activities.The research project focuses on understanding the impact of distorted coordination environments - a ubiquitous feature of active sites in metalloproteins in living organisms - on the reactivity using a combination of synthetic inorganic and theoretical methods. The key concept is that bioinspired catalysts supported by symmetric organic/organometallic ligands cannot sufficiently model the electronic structure details that are frequently important for executing biological functions. The research project focuses on understanding how the reactivity of synthetic model complexes changes as a function of geometric distortion. Specifically, the research will evaluate the effect of distorted coordination environments inspired by protein active sites on: (1) the interconversion of nitrite (NO2-) and nitric oxide (NO) catalyzed by a copper nitrosyl complex modelled after the active site of ceruloplasmin (Cp) and copper nitrite reductase (CuNiR); (2) the challenging sp3 C-H hydroxylation catalyzed by copper-oxo complexes modeled after the active site of particulate methane monooxygenase (pMMO); (3) selective four-electron reduction of oxygen to water catalyzed by a site-differentiated tricopper-oxo cluster modelled after the trinuclear copper site in multicopper oxidase (MCO). The study will exploit structure-function relationships of enzymes and will be directed towards the identification of new strategies to reproduce the reactivity of enzymes and the discovery of broadly generalizable rules for catalyst design that are applicable beyond the scope of the biological systems used as inspiration.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.