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

Mononuclear nonheme iron(III)-peroxo complexes bearing N -tetramethylated cyclam ( n -TMC) ligands, [Fe III (O 2 )( n -TMC)] + ( n = 12, 13, and 14), have recently shown highly intriguing reactivities in various oxidation reactions, such as the cis -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 (O 2 )( n -TMC)] + mediated N -demethylation of N, N -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 (O 2 )( n -TMC)] +, thereby establishing an electron-transfer (ET) pathway for the N -demethylation reaction. Investigation of the ET reactivity of [Fe III (O 2 )( n -TMC)] + in light of the Marcus theory of ET, and a comparison of the N -demethylation and the ET rate constants corroborate a mechanism, whereby N -demethylation of DMAs by [Fe III (O 2 )( n -TMC)] + proceeds via the peroxide O–O bond cleavage of [Fe III (O 2 )( n -TMC)] + to form a transient [Fe IV (O 2– )(O • – )( n -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 • – )( n -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 N -demethylation reaction.