Research

Biomimetic small molecule activation by metal-oxygen complexes

Debate of Nucleophilic versus Electrophilic Oxidative Aldehyde Deformylation by Mononuclear Nonheme Iron(III)-Peroxo and Iron(IV)-Oxo Complexes

High-valent iron(IV)-oxo species are fleeting intermediates that perform vital reactions in enzymatic catalysis. In contrast, heme and nonheme iron(III)-peroxo intermediates usually act as nucleophiles and are converted to high-valent iron-oxo intermediates for electrophilic oxidation reactions. Herein, we report a study on aldehyde deformylation reactions of 2-phenylpropionaldehyde (2-PPA) and its derivatives by iron(III)-peroxo complexes bearing tetramethylated cyclam (TMC) analogues, including [FeIII(O2)(12-TMC)]+ (1), [FeIII(O2)(13-TMC)]+ (2), and [FeIII(O2)(14-TMC)]+ (3). Reactivity studies by employing deuterated substrates, such as α-[D1]-2-phenylpropionaldehyde and aldehyde-[D]-2-phenylpropionaldehyde, demonstrate that deformylation of 2-PPA by the nonheme iron(III)-peroxo complexes occurs via abstraction of the stronger aldehyde C–H atom, rather than the expected nucleophilic attack or weaker α-C–H atom abstraction reactions. Interestingly, the preference for aldehyde C–H atom abstraction is retained during the deformylation of 2-PPA by iron(IV)-oxo complexes, i.e., [FeIV(O)(13-TMC)]2+ (4) and [FeIV(O)(N4Py)]2+ (5). DFT calculations reproduce the experimental trends in reactivity and reveal that the peroxide O–O bond is cleaved to form an iron(III)-dioxyl species that conducts aldehyde C–H bond abstraction; this chemoselectivity is achieved through stabilizing noncovalent interactions between the oxidants and the aromatic ring of the substrate that positions the aldehyde in close proximity to the FeIII–O2/FeIV═O cores. These new experimental and theoretical findings together with the previous demonstrations of the ability of 1–3 in hydrogen atom transfer, oxygen atom transfer, and cis-dihydroxylation reactions highlight that iron(III)-peroxo cores are not inherently nucleophiles and can have more important functions in chemical and biological oxidation reactions, rather than acting as transient species en route to high-valent metal–oxo intermediates.

Influence of induced steric on the switchover reactivity of mononuclear Cu(II)-alkylperoxo complexes

Coordination and the steric environment around a metal center play an indispensable role in its reactivity. In this report, we have synthesized two bispidine-based Cu(II)-OOR (R = tBu) complexes, [Cu(L1)(OOtBu)]+ and [Cu(L2)(OOtBu)]+, characterized by different steric environments around the metal center and characterized by various spectroscopic techniques. These Cu(II)-OOR species show reactivity towards oxygen atom transfer and aldehyde deformylation reactions. In contrast to the previously reported nucleophilic oxidation, aldehyde deformylation reaction by these complexes proceeds via an initial H-atom abstraction with a KIE of 12 and 8, respectively. It has been observed that more steric bulk at the N3 and N7 positions of the bispidine ligand prefers the oxygen atom transfer reaction, while it hinders the H-atom abstraction for Cu(II)-alkylperoxo complexes.

Dramatic rate-enhancement of oxygen atom transfer by an iron(iv)-oxo species by equatorial ligand field perturbations

Nonheme iron dioxygenases are efficient enzymes with relevance for human health that regio- and stereospecifically transfer an oxygen atom to substrates. How they perform this task with such selectivity remains unknown, but may have to do with substrate binding, positioning, and oxidant approach. To understand substrate approach on a catalytic reaction centre, we investigated the structure and reactivity of a biomimetic oxidant with ligand features that affect the interactions between oxidant and substrate. Thus, we report here the synthesis and characterization of an iron(IV)-oxo complex with a pentadentate nonheme ligand, where structurally induced perturbations in the equatorial ligand field affect the spectroscopy and reactivity of the complex. We tested the activity of the complex with respect to oxygen atom transfer to and hydrogen atom abstraction from substrates. This oxidant exhibits improved reaction rates toward heteroatom oxidation compared to the nonsubstituted ligand complex by ∼approximately 104-fold. The origin of the enhanced reactivity is explained with a series of density functional theory studies that show an enhanced electron affinity of the oxidant through equatorial ligand perturbations.

Deformylation Reaction by a Nonheme Manganese(III)–Peroxo Complex via Initial Hydrogen-Atom Abstraction

Metal–peroxo intermediates are key species in the catalytic cycles of nonheme metalloenzymes, but their chemical properties and reactivity patterns are still poorly understood. The synthesis and characterization of a manganese(III)–peroxo complex with a pentadentate bispidine ligand system and its reactivity with aldehydes was studied. Manganese(III)–peroxo can react through hydrogen-atom abstraction reactions instead of the commonly proposed nucleophilic addition reaction. Evidence of the mechanism comes from experiments which identify a primary kinetic isotope effect of 5.4 for the deformylation reaction. Computational modeling supports the established mechanism and identifies the origin of the reactivity preference of hydrogen-atom abstraction over nucleophilic addition.

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