Mononuclear Non-Heme Iron(III)-Peroxo Complexes in Oxidative <i>N</i> -Demethylation Reaction as a Chemical Model Study of Rieske Oxygenases

Mononuclear nonheme iron(III)-peroxo complexes bearing <i>N</i>-tetramethylated cyclam (<i>n</i>-TMC) ligands, [Fe^III(O₂)(<i>n</i>-TMC)]⁺ (<i>n</i> = 12, 13, and 14), have recently shown highly intriguing reactivities in various oxidation reactions, such as the <i>cis</i>-dihydroxylation and C-H functionalization reactions, which were previously associated only with high-valent iron-oxo intermediates in heme and nonheme iron enzymes. Herein, we extend our study to report [Fe^III(O₂)(<i>n</i>-TMC)]⁺ mediated <i>N</i>-demethylation of <i>N</i>,<i>N</i>-dimethylanilines (DMAs), another reaction that was previously associated only with high-valent iron-oxo cores. Most importantly, we provide definitive evidence of the occurrence of electron transfer from DMAs to [Fe^III(O₂)(<i>n</i>-TMC)]⁺, thereby establishing an electron-transfer (ET) pathway for the <i>N</i>-demethylation reaction. Investigation of the ET reactivity of [Fe^III(O₂)(<i>n</i>-TMC)]⁺ in light of the Marcus theory of ET, and a comparison of the <i>N</i>-demethylation and the ET rate constants corroborate a mechanism, whereby <i>N</i>-demethylation of DMAs by [Fe^III(O₂)(<i>n</i>-TMC)]⁺ proceeds via the peroxide O-O bond cleavage of [Fe^III(O₂)(<i>n</i>-TMC)]⁺ to form a transient [Fe^IV(O^2-)(O^{• -})(<i>n</i>-TMC)]⁺ species, which undergoes a proton-coupled electron-transfer (PCET) or an uncoupled electron transfer-proton transfer (ET/PT) in the presence of DMAs. Saturation kinetics support the rate-determining formation of [Fe^IV(O^2-)(O^{• -})(<i>n</i>-TMC)]⁺ in a pre-equilibrium step with the same values of the O-O bond cleavage rate constants irrespective of the substrates, such as DMAs and one-electron oxidants. The present study corroborates that mononuclear nonheme iron(III)-peroxo cores are not mere pass-through points en route to high-valent metal-oxo intermediates, but they can play an important role in the diverse oxidation reactions of Rieske oxygenases, such as in the <i>N</i>-demethylation reaction.