Biomimetic modeling is a useful tool for studying enzymatic systems by creating synthetic analogues of an enzyme’s active site. This talk details three years of undergraduate research focused on modeling the active site of Acireductone dioxygenase (ARD), a metalloenzyme that plays a key role in the methionine salvage pathway by catalyzing the oxidative carbon-carbon bond cleavage of acireductone. ARD is unique in that it performs dual chemistry based solely on the metal ion bound to its active site, leading to both on-pathway and off-pathway reactions that result in different products. The off-pathway reaction in bacteria is performed by Ni-ARD, and recent studies have shown that Mn and Co-ARD perform the same off-pathway chemistry in mammalian systems. In order to investigate why this dual chemistry occurs and to better understand the structure-function relationship of the native enzyme, small molecular models of the active sites of both Ni-ARD and Mn-ARD were synthesized using pyridine based, Schiff-base, N4O chelating ligands. Reactivity studies of these metal complexes with a model substrate were performed and analyzed using spectroscopic techniques. Results point towards the metal-mediated catalytic C-C bond cleavage of the model substrate, which was corroborated computationally. The oxidative chemistry performed by the model systems holds potential biological implications for understanding the mechanism of ARD and other oxygenases in general.

Mn(II) and Ni(II) based model complexes of the active site of Acireductone dioxygenase (ARD): My undergraduate research adventures into the world of bioinorganic modeling chemistry

ACS Fall 2021

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