Mononuclear nonheme iron dioxygenases (MNIDs) play a central role in amino acid catabolism, the microbial synthesis of complex natural products, and the bioremediation of organic pollutants by soil bacteria. These enzymes feature a high-spin monoiron(II) center bound facially to a 2His1X triad of protein-derived ligands (where X = Glu, Asp, or His), and follow an ordered mechanism in which the coordination of substrate primes the Fe(II) center for O2 binding. It has been proposed that the substrate develops (partial) radical character in the resulting Fe/O2 adduct, thereby facilitating bond formation between the superoxo and substrate ligands. However, this hypothesis has been difficult to confirm due to the elusiveness of the putative intermediate. We have prepared structural and functional models of several MNIDs, including gentisate 1,2-dioxygenase (GDO) and cysteine dioxygenase (CDO), with the aim of obtaining fundamental insights into their catalytic mechanisms. This report summarizes spectroscopic and computational studies of species that resemble the proposed dioxygen-bound intermediate of the enzymes. The resulting electronic-structure descriptions are then used rationalize kinetic parameters measured for the reaction of the active-site models with O2. The spectroscopic and reactivity properties of the synthetic complexes are compared to those exhibited by the corresponding enzymes, thereby elucidating the impact of outer-sphere residues on the geometric and electronic structures of iron sites.

Relationship between electronic structure and reactivity in nonheme dioxygenase models

253rd National Meeting (2017)

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