cis -Dihydroxylation by Synthetic Iron(III)-Peroxo Intermediates and Rieske Dioxygenases: Experimental and Theoretical Approaches Reveal the Key O-O Bond Activation Step.

Dioxygen (O ₂ ) activation by iron-containing enzymes and biomimetic compounds generates iron-oxygen intermediates, such as iron-superoxo, -peroxo, -hydroperoxo, and -oxo, that mediate oxidative reactions in biological and abiological systems. Among the iron-oxygen intermediates, iron(III)-peroxo species are less frequently implicated as active intermediates in oxidation reactions. In this study, we present the combined experimental and theoretical investigations on cis -dihydroxylation reactions mediated by synthetic mononuclear nonheme iron-peroxo intermediates, demonstrating the importance of supporting ligands and metal centers in activating the peroxo ligand toward the O-O bond homolysis for the cis -dihydroxylation reactions. We found a significant ring size effect of the TMC ligand in [Fe ^III (O ₂ )( n -TMC)] ⁺ (TMC = tetramethylated tetraazacycloalkane; n = 12, 13, and 14) on the cis -dihydroxylation reactivity order: [Fe ^III (O ₂ )(12-TMC)] ⁺ > [Fe ^III (O ₂ )(13-TMC)] ⁺ > [Fe ^III( O ₂ )(14-TMC)] ⁺ . Additionally, we found that only [Fe ^III (O ₂ )( n -TMC)] ⁺ , but not other metal-peroxo complexes such as [M ^III (O ₂ )( n -TMC)] ⁺ (M = Mn, Co, and Ni), is reactive for the cis -dihydroxylation of olefins. Using density functional theory (DFT) calculations, we revealed that electron transfer from the Fe d _xz orbital to the peroxo σ*(O-O) orbital facilitates the O-O bond homolysis, with the O-O bond cleavage barrier well correlated with the energy gap between the frontier molecular orbitals of d _xz and σ*(O-O). Further computational studies showed that the reactivity of the synthetic [Fe ^III (O ₂ )(12-TMC)] ⁺ complex is comparable to that of Rieske dioxygenases in cis -dihydroxylation, providing compelling evidence of the potential involvement of Fe(III)-peroxo species in Rieske dioxygenases. Thus, the present results significantly advance our understanding of the cis -dihydroxylation mechanisms by Rieske dioxygenases and synthetic nonheme iron-peroxo models.