The successful development of artificial metalloenzymes tests our understanding of enzymatic catalysis, protein folding, and bioinorganic chemistry. A distinct and unmet challenge in this arena is the development of redox-active, artificial metalloenzymes that exhibit catalytic activity with small molecules. Nature employs a diverse array of copper-containing enzymes that make use of the tunable redox properties of this ubiquitous metal ion. This proposal outlines the design of flexible metal binding sites that accommodate two redox-active and coordinatively-unsaturated copper ions at the interface of complementary protein monomers or within a reengineered maltose binding receptor protein. These designs will be guided by computational methods, X-ray crystallography and bimetallic templating strategies. As a test for the catalytic properties of the designed site, we will investigate the CuI2- catalyzed reductive coupling of CO2 to oxalate.
Metalloenzymes mediate many chemical transformations that are essential to life on this planet. The successful design of artificial redox-active metalloenzymes remains a significant challenge in protein design. This proposal aims to prepare artificial dicopper enzymes that catalyze the multielectron reduction of two CO2 molecules to oxalate.
|Hernandez, Lucas W; Pospech, Jola; Klöckner, Ulrich et al. (2017) Synthesis of (+)-Pancratistatins via Catalytic Desymmetrization of Benzene. J Am Chem Soc 139:15656-15659|