Manganese-Substituted Polyoxometalates as Functional Mimics of Indole Dioxygenase Enzymes

Dioxygenase reactivity, where both oxygen atoms of O₂ are incorporated into an organic product, is a relative rarity. Notable is the indoleamine 2,3-dioxygenase enzyme with an iron-heme active site. Biomimetic studies using iron and manganese porphyrins have been successful and mechanistically enriching. We show that inorganic manganese-substituted polyoxometalates are also effective functional mimics of indoleamine 2,3-dioxygenases. Thus, several mono-, di-, and tri-Mn^II-substituted polyoxometalates were reacted with O₂, and the intermediacy of a superoxide species was supported by both EPR spectroscopy using 5-tert-butoxycarbonyl-5-methyl-1-pyrroline-N-oxide as a spin trap and cyclic voltammetry. Further experiments with 2,3-dimethyl-1H-indole yielded the expected dioxygenated product, N-(2-acetylphenyl)acetamide, in high yields under O₂. Oxygen isotope labeling experiments and the use of triphenylphosphine as a probe supported a stepwise oxygenation process with formation of two suggested manganese-centered intermediates as also shown for porphyrin/heme-based catalysts. Using a combination of UV-vis and EPR measurements, it was concluded that after a first oxygen donation by a Mn(III)-superoxo species, a second oxygen-donated species, best formulated as a Mn(III)-oxyl species rather than a Mn(IV)-oxo species, yielded the final dioxygenated product. The research supports the notion that inorganic manganese polyoxometalates with an oxotungstate framework are true functional models of indoleamine 2,3-dioxygenases.