Electronic Structure and Reactivity of Dioxygen-Derived Aliphatic Thiolate-Ligated Fe-Peroxo and Fe(IV) Oxo Compounds.

Herein, we examine the electronic and geometric structural properties of O2-derived aliphatic thiolate-ligated Fe-peroxo, Fe-hydroxo, and Fe(IV) oxo compounds. The latter cleaves strong C-H bonds (96 kcal mol-1) on par with the valine C-H bond cleaved by isopencillin N synthase (IPNS). Stopped-flow kinetics studies indicate that the barrier to O2 binding to [FeII(SMe2N4(tren))]+ (3) is extremely low (Ea = 36(2) kJ mol-1), as theoretically predicted for IPNS. Dioxygen binding to 3 is shown to be reversible, and a superoxo intermediate, [FeIII(SMe2N4(tren))(O2)]+ (6), forms in the first 25 ms of the reaction at -40 °C prior to the rate-determining (Ea = 46(2) kJ mol-1) formation of peroxo-bridged [(SMe2N4(tren))Fe(III)]2(µ-O2)2+ (7). A log(kobs) vs log([Fe]) plot for the formation of 7 is consistent with the second-order dependence on iron, and H2O2 assays are consistent with a 2:1 ratio of Fe/H2O2. Peroxo 7 is shown to convert to ferric-hydroxo [FeIII(SMe2N(tren))(OH)]+ (9, g⊥ = 2.24, g∥ = 1.96), the identity of which was determined via its independent synthesis. Rates of the conversion 7 → 9 are shown to be dependent on the X-H bond strength of the H-atom donor, with a kH/kD = 4 when CD3OD is used in place of CH3OH as a solvent. A crystallographically characterized cis thiolate-ligated high-valent iron oxo, [FeIV(O)(SMe2N4(tren))]+ (11), is shown to form en route to hydroxo 9. Electronic structure calculations were shown to be consistent with 11 being an S = 1 Fe(IV)═O with an unusually high νFe-O stretching frequency at 918 cm-1 in line with the extremely short Fe-O bond (1.603(7) Å).

Superoxide Oxidation by a Thiolate-Ligated Iron Complex and Anion Inhibition.

Superoxide (O2•-) is a toxic radical, generated via the adventitious reduction of dioxygen (O2), which has been implicated in a number of human disease states. Nonheme iron enzymes, superoxide reductase (SOR) and superoxide dismutase (SOD), detoxify O2•- via reduction to afford H2O2 and disproportionation to afford O2 and H2O2, respectively. The former contains a thiolate in the coordination sphere, which has been proposed to prevent O2•- oxidation to O2. The work described herein shows that, in contrast to this, oxidized thiolate-ligated [FeIII(SMe2N4(tren)(THF)]2+ (1ox-THF) is capable of oxidizing O2•- to O2. Coordinating anions, Cl- and OAc-, are shown to inhibit dioxygen evolution, implicating an inner-sphere mechanism. Previously we showed that the reduced thiolate-ligated [FeII(SMe2N4(tren))]+ (1) is capable of reducing O2•- via a proton-dependent inner-sphere mechanism involving a transient Fe(III)-OOH intermediate. A transient ferric-superoxo intermediate, [FeIII(SMe2N4(tren))(O2)]+ (3), is detected by electronic absorption spectroscopy at -130 °C in the reaction between 1ox-THF and KO2 and shown to evolve O2 upon slight warming to -115 °C. The DFT calculated O-O (1.306 Å) and Fe-O (1.943 Å) bond lengths of 3 are typical of ferric-superoxo complexes, and the time-dependent DFT calculated electronic absorption spectrum of 3 reproduces the experimental spectrum. The electronic structure of 3 is shown to consist of two antiferromagnetically coupled (Jcalc = -180 cm-1) unpaired electrons, one in a superoxo π*(O-O) orbital and the other in an antibonding π*(Fe(dyz)-S(py)) orbital.

How Metal Ion Lewis Acidity and Steric Properties Influence the Barrier to Dioxygen Binding, Peroxo O-O Bond Cleavage, and Reactivity.

Herein we quantitatively investigate how metal ion Lewis acidity and steric properties influence the kinetics and thermodynamics of dioxygen binding versus release from structurally analogous Mn-O2 complexes, as well as the barrier to Mn peroxo O-O bond cleavage, and the reactivity of Mn oxo intermediates. Previously we demonstrated that the steric and electronic properties of MnIII-OOR complexes containing N-heterocyclic (NAr) ligand scaffolds can have a dramatic influence on alkylperoxo O-O bond lengths and the barrier to alkylperoxo O-O bond cleavage. Herein, we examine the dioxygen reactivity of a new MnII complex containing a more electron-rich, less sterically demanding NAr ligand scaffold, and compare it with previously reported MnII complexes. Dioxygen binding is shown to be reversible with complexes containing the more electron-rich metal ions. The kinetic barrier to O2 binding and peroxo O-O bond cleavage is shown to correlate with redox potentials, as well as the steric properties of the supporting NAr ligands. The reaction landscape for the dioxygen chemistry of the more electron-rich complexes is shown to be relatively flat. A total of four intermediates, including a superoxo and peroxo species, are observed with the most electron-rich complex. Two new intermediates are shown to form following the peroxo, which are capable of cleaving strong X-H bonds. In the absence of a sacrificial H atom donor, solvent, or ligand, serves as a source of H atoms. With TEMPOH as sacrificial H atom donor, a deuterium isotope effect is observed (kH/kD = 3.5), implicating a hydrogen atom transfer (HAT) mechanism. With 1,4-cyclohexadiene, 0.5 equiv of benzene is produced prior to the formation of an EPR detected MnIIIMnIV bimetallic species, and 0.5 equiv after its formation.

Geometric and electronic structure of a crystallographically characterized thiolate-ligated binuclear peroxo-bridged cobalt(III) complex.

In order to shed light on metal-dependent mechanisms for O-O bond cleavage, and its microscopic reverse, we compare herein the electronic and geometric structures of O2-derived binuclear Co(III)- and Mn(III)-peroxo compounds. Binuclear metal peroxo complexes are proposed to form as intermediates during Mn-promoted photosynthetic H2O oxidation, and a Co-containing artificial leaf inspired by nature's photosynthetic H2O oxidation catalyst. Crystallographic characterization of an extremely activated peroxo is made possible by working with substitution-inert, low-spin Co(III). Density functional theory (DFT) calculations show that the frontier orbitals of the Co(III)-peroxo compound differ noticeably from the analogous Mn(III)-peroxo compound. The highest occupied molecular orbital (HOMO) associated with the Co(III)-peroxo is more localized on the peroxo in an antibonding π*(O-O) orbital, whereas the HOMO of the structurally analogous Mn(III)-peroxo is delocalized over both the metal d-orbitals and peroxo π*(O-O) orbital. With low-spin d6 Co(III), filled t2g orbitals prevent π-back-donation from the doubly occupied antibonding π*(O-O) orbital onto the metal ion. This is not the case with high-spin d4 Mn(III), since these orbitals are half-filled. This weakens the peroxo O-O bond of the former relative to the latter.

Formation of a Reactive, Alkyl Thiolate-Ligated FeIII-Superoxo Intermediate Derived from Dioxygen.

Herein, we describe an alkyl thiolate-ligated iron complex that reacts with dioxygen to form an unprecedented example of an iron superoxo (O2•-) intermediate, [FeIII(S2Me2N3(Pr,Pr))(O2)] (4), which is capable of cleaving strong C-H bonds. A cysteinate-ligated iron superoxo intermediate is proposed to play a key role in the biosynthesis of ß-lactam antibiotics by isopenicillin N-synthase (IPNS). Superoxo 4 converts to a metastable putative Fe(III)-OOH intermediate, at rates that are dependent on the C-H bond strength of the H atom donor, with a kinetic isotope effect ( kH/ kD = 4.8) comparable to that of IPNS ( kH/ kD = 5.6). The bond dissociation energy of the C-H bonds cleaved by 4 (92 kcal/mol) is comparable to C-H bonds cleaved by IPNS (93 kcal/mol). Both the calculated and experimental electronic absorption spectra of 4 are comparable to those of the putative IPNS superoxo intermediate, and are shown to involve RS- → Fe-O2•- and O2•- → Fe charge transfer transitions. The π-back-donation by the electron-rich alkyl thiolate presumably facilitates this reactivity by increasing the basicity of the distal oxygen. The frontier orbitals of 4 are shown to consist of two strongly coupled unpaired electrons of opposite spin, one in a superoxo π*(O-O) orbital, and the other in an Fe(d xy) orbital.