Reactivity and O₂ Formation by Mn(IV)- and Mn(V)-Hydroxo Species Stabilized within a Polyfluoroxometalate Framework

Manganese­(IV,V)-hydroxo and oxo complexes are often implicated in both catalytic oxygenation and water oxidation reactions. Much of the research in this area is designed to structurally and/or functionally mimic enzymes. On the other hand, the tendency of such mimics to decompose under strong oxidizing conditions makes the use of molecular inorganic oxide clusters an enticing alternative for practical applications. In this context it is important to understand the reactivity of conceivable reactive intermediates in such an oxide-based chemical environment. Herein, a polyfluoroxometalate (PFOM) monosubstituted with manganese, [NaH₂(Mn-L)­W₁₇F₆O₅₅]^q–, has allowed the isolation of a series of compounds, Mn­(II, III, IV and V), within the PFOM framework. Magnetic susceptibility measurements show that all the compounds are high spin. XPS and XANES measurements confirmed the assigned oxidation states. EXAFS measurements indicate that Mn­(II)­PFOM and Mn­(III)­PFOM have terminal aqua ligands and Mn­(V)­PFOM has a terminal hydroxo ligand. The data are more ambiguous for Mn­(IV)­PFOM where both terminal aqua and hydroxo ligands can be rationalized, but the reactivity observed more likely supports a formulation of Mn­(IV)­PFOM as having a terminal hydroxo ligand. Reactivity studies in water showed unexpectedly that both Mn­(IV)-OH-PFOM and Mn­(V)-OH-PFOM are very poor oxygen-atom donors; however, both are highly reactive in electron transfer oxidations such as the oxidation of 3-mercaptopropionic acid to the corresponding disulfide. The Mn­(IV)-OH-PFOM compound reacted in water to form O₂, while Mn­(V)-OH-PFOM was surprisingly indefinitely stable. It was observed that addition of alkali cations (K⁺, Rb⁺, and Cs⁺) led to the aggregation of Mn­(IV)-OH-PFOM as analyzed by electron microscopy and DOSY NMR, while addition of Li⁺ and Na⁺ did not lead to aggregates. Aggregation leads to a lowering of the entropic barrier of the reaction without changing the free energy barrier. The observation that O₂ formation is fastest in the presence of Cs⁺ and ∼fourth order in Mn­(IV)-OH-PFOM supports a notion of a tetramolecular Mn­(IV)-hydroxo intermediate that is viable for O₂ formation in an oxide-based chemical environment. A bimolecular reaction mechanism involving a Mn­(IV)-hydroxo based intermediate appears to be slower for O₂ formation

Characterization of the Fleeting Hydroxoiron(III) Complex of the Pentadentate TMC-py Ligand

Nonheme mononuclear hydroxoiron­(III) species are important intermediates in biological oxidations, but well-characterized examples of synthetic complexes are scarce due to their instability or tendency to form μ-oxodiiron­(III) complexes, which are the thermodynamic sink for such chemistry. Herein, we report the successful stabilization and characterization of a mononuclear hydroxoiron­(III) complex, [Fe^III(OH)­(TMC-py)]²⁺ (<b>3</b>; TMC-py = 1<i>-</i>(pyridyl-2′-methyl)-4,8,11-trimethyl-1,4,8,11-tetrazacyclotetradecane), which is directly generated from the reaction of [Fe^IV(O)­(TMC-py)]²⁺ (<b>2</b>) with 1,4-cyclohexadiene at −40 °C by H-atom abstraction. Complex <b>3</b> exhibits a UV spectrum with a λ_max at 335 nm (ε ≈ 3500 M^–1 cm^–1) and a molecular ion in its electrospray ionization mass spectrum at <i>m</i>/<i>z</i> 555 with an isotope distribution pattern consistent with its formulation. Electron paramagnetic resonance and Mössbauer spectroscopy show <b>3</b> to be a high-spin Fe­(III) center that is formed in 85% yield. Extended X-ray absorption fine structure analysis reveals an Fe–OH bond distance of 1.84 Å, which is also found in [(TMC-py)­Fe^III–O–Cr^III(OTf)₃]⁺ (<b>4</b>) obtained from the reaction of <b>2</b> with Cr­(OTf)₂. The <i>S</i> = 5/2 spin ground state and the 1.84 Å Fe–OH bond distance are supported computationally. Complex <b>3</b> reacts with 1-hydroxy-2,2,6,6-tetramethylpiperidine (TEMPOH) at −40 °C with a second-order rate constant of 7.1 M^–1 s^–1 and an OH/OD kinetic isotope effect value of 6. On the basis of density functional theory calculations, the reaction between <b>3</b> and TEMPOH is classified as a proton-coupled electron transfer as opposed to a hydrogen-atom transfer

The Two Faces of Tetramethylcyclam in Iron Chemistry: Distinct Fe–O–M Complexes Derived from [Fe^IV(O_{<i>anti</i>/<i>syn</i>})(TMC)]²⁺ Isomers

Tetramethylcyclam (TMC, 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) exhibits two faces in supporting an oxoiron­(IV) moiety, as exemplified by the prototypical [(TMC)­Fe^IV(O_<i>anti</i>)­(NCCH₃)]­(OTf)₂, where <i>anti</i> indicates that the O atom is located on the face opposite all four methyl groups, and the recently reported <i>syn</i> isomer [(TMC)­Fe^IV(O_<i>syn</i>)­(OTf)]­(OTf). The ability to access two isomers of [(TMC)­Fe^IV(O_{<i>anti</i>/<i>syn</i>})] raises the fundamental question of how ligand topology can affect the properties of the metal center. Previously, we have reported the formation of [(CH₃CN)­(TMC)­Fe^III–O_<i>anti</i>–Cr^III(OTf)₄(NCCH₃)] (<b>1</b>) by inner-sphere electron transfer between Cr­(OTf)₂ and [(TMC)­Fe^IV(O_<i>anti</i>)­(NCCH₃)]­(OTf)₂. Herein we demonstrate that a new species <b>2</b> is generated from the reaction between Cr­(OTf)₂ and [(TMC)­Fe^IV(O_<i>syn</i>)­(NCCH₃)]­(OTf)₂, which is formulated as [(TMC)­Fe^III–O_<i>syn</i>–Cr^III(OTf)₄(NCCH₃)] based on its characterization by UV–vis, resonance Raman, Mössbauer, and X-ray absorption spectroscopic methods, as well as electrospray mass spectrometry. Its pre-edge area (30 units) and Fe–O distance (1.77 Å) determined by X-ray absorption spectroscopy are distinctly different from those of <b>1</b> (11-unit pre-edge area and 1.81 Å Fe–O distance) but more closely resemble the values reported for [(TMC)­Fe^III–O_<i>syn</i>–Sc^III(OTf)₄(NCCH₃)] (<b>3</b>, 32-unit pre-edge area and 1.75 Å Fe–O distance). This comparison suggests that <b>2</b> has a square pyramidal iron center like <b>3</b>, rather than the six-coordinate center deduced for <b>1</b>. Density functional theory calculations further validate the structures for <b>1</b> and <b>2</b>. The influence of the distinct TMC topologies on the coordination geometries is further confirmed by the crystal structures of [(Cl)­(TMC)­Fe^III–O_<i>anti</i>–Fe^IIICl₃] (<b>4</b>_<b>Cl</b>) and [(TMC)­Fe^III–O_<i>syn</i>–Fe^IIICl₃]­(OTf) (<b>5</b>). Complexes <b>1</b>–<b>5</b> thus constitute a set of complexes that shed light on ligand topology effects on the coordination chemistry of the oxoiron moiety

Descriptive characteristics of the UK Biobank participants (N = 424,439) included in PheWAS analyses.

Descriptive characteristics of the UK Biobank participants (N = 424,439) included in PheWAS analyses.</p

IVW MR and weighted median MR estimates for the outcomes reaching 5% FDR significance where there was no evidence of heterogeneity as determined by the Cochran Q test.

IVW MR and weighted median MR estimates for the outcomes reaching 5% FDR significance where there was no evidence of heterogeneity as determined by the Cochran Q test.</p

Forest plot of results for traits related to hypercholesterolemia for which there was evidence across the 3 genetic instruments for a causal effect of higher iron status.

The ORs are reported as MR estimates corresponding to 1 SD increase in serum iron. MR, mendelian randomization; OR, odds ratio; SD, standard deviation.</p

Forest plot of results for traits related to skin and skin structure infections for which there was evidence across the 3 genetic instruments for a causal effect of higher iron status.

The ORs are reported as MR estimates corresponding to 1 SD increase in serum iron. MR, mendelian randomization; OR, odds ratio; SD, standard deviation.</p

The number of phenotypes and cases considered in each disease category.

The number of phenotypes and cases considered in each disease category.</p

Forest plot of results for traits related to anemia for which there was evidence across the 3 genetic instruments for a causal effect of higher iron status.

The ORs are reported as MR estimates corresponding to 1 SD increase in serum iron. MR, mendelian randomization; OR, odds ratio; SD, standard deviation.</p