Central Iron Atom Research Articles

PF497 INFLAMMATION‐DRIVEN HEME/IRON CYTOTOXICITY IN PARKINSON'S DISEASE

Background:Heme is a metallo‐compound, essential for the survival of most organisms. However, the ability of the central iron (Fe) atom, contained within its protoporphyrin ring, to participate in the Fenton reaction and generate highly reactive hydroxyl radicals renders heme potentially toxic. Under inflammatory conditions, the release of heme from hemoproteins leads to an exacerbated oxidative stress, a deleterious effect associated with tissue damage and disease severity.Aims:As immune‐mediated inflammatory diseases often cause a certain degree of hemolysis and vascular leakage, it is reasonable to assume that the cytotoxicity of heme/Fe may also affect less accessible organs, such as the brain, thus increasing the risk and severity of neurodegenerative diseases.Methods:This hypothesis has been investigated in mice, in which the exogenous administration of heme or the release of this molecule upon inflammation/infectionwas shown to enhance the severity of Parkinson's disease (PD). An increased susceptibility to pharmacologic PD was observed when mice are exposed to heme and subsequently treated with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), a neurotoxin precursor that, once converted into the active metabolite, irreversibly damages the dopaminergic neurons (DNs).Results:Our results demonstrate that from circulation, heme is capable to enter the brain and trigger neuroinflammation. While this is associated with the recruitment of immune cells, which breach the BBB and enter the brain, an increased level of circulating heme was shown to contribute to the occurrence of brain Fe overload, causing an exacerbated locomotor dysfunction in response to PD induction.Summary/Conclusion:Therefore, our findings suggest that the release of heme in circulation upon immune‐mediated inflammatory diseases is capable to prime the brain and contribute to the development of neurodegenerative diseases, such as PD.

Air‐Free Synthesis of a Ferrous Metal‐Organic Framework Featuring HKUST‐1 Structure and its Mössbauer Spectrum

Single crystals of the FeII metal‐organic framework (MOF) with 1,3,5‐benzenetricarboxylate (BTC) as a linker were solvothermally obtained under air‐free conditions. X‐ray diffraction analysis of the crystals demonstrated a structure for FeII‐MOF analogous to that of [Cu3(BTC)2] (HKUST‐1). Unlike HKUST‐1, however, the FeII‐MOF did not retain permanent porosity after exchange of guest molecules. The Mössbauer spectrum of the FeII‐MOF was recorded at 80 K in zero field yielding an apparent quadrupole splitting of ΔEQ = 2.43 mm·s–1, and an isomer shift of δ = 1.20 mm·s–1, consistent with high‐spin central iron(II) atoms. Air exposure of the FeII‐MOF was found to result in oxidation of the metal atoms to afford FeIII. These results demonstrate that FeII‐based MOFs can be prepared in similar fashion to the [Cu3(BTC)2], but that they lack permanent porosity when degassed.

Visualizing the iron atom exchange front in the Fe(II)-catalyzed recrystallization of goethite by atom probe tomography

The autocatalytic redox interaction between aqueous Fe(II) and Fe(III)-(oxyhydr)oxide minerals such as goethite and hematite leads to rapid recrystallization marked, in principle, by an atom exchange (AE) front, according to bulk iron isotopic tracer studies. However, direct evidence for this AE front has been elusive given the analytical challenges of mass-resolved imaging at the nanoscale on individual crystallites. We report successful isolation and characterization of the AE front in goethite microrods by 3D atom probe tomography (APT). The microrods were reacted with Fe(II) enriched in tracer 57Fe at conditions consistent with prior bulk studies. APT analyses and 3D reconstructions on cross-sections of the microrods reveal an AE front that is spatially heterogeneous, at times penetrating several nanometers into the lattice, in a manner consistent with defect-accelerated exchange. Evidence for exchange along microstructural domain boundaries was also found, suggesting another important link between exchange extent and initial defect content. The findings provide an unprecedented view into the spatial and temporal characteristics of Fe(II)-catalyzed recrystallization at the atomic scale, and substantiate speculation regarding the role of defects controlling the dynamics of electron transfer and AE interaction at this important redox interface.

Impact of Organic Matter on Iron(II)-Catalyzed Mineral Transformations in Ferrihydrite-Organic Matter Coprecipitates.

Poorly crystalline Fe(III) (oxyhydr)oxides like ferrihydrite are abundant in soils and sediments and are often associated with organic matter (OM) in the form of mineral-organic aggregates. Under anoxic conditions, interactions between aqueous Fe(II) and ferrihydrite lead to the formation of crystalline secondary minerals, like lepidocrocite, goethite, or magnetite. However, the extent to which Fe(II)-catalyzed mineral transformations are influenced by ferrihydrite-associated OM is not well understood. We therefore reacted ferrihydrite-PGA coprecipitates (PGA = polygalacturonic acid, C:Fe molar ratios = 0-2.5) and natural Fe-rich organic flocs (C:Fe molar ratio = 2.2) with 0.5-5.0 mM isotopically labeled 57Fe(II) at pH 7 for 5 weeks. Relying on the combination of stable Fe isotope tracers, a novel application of the PONKCS method to Rietveld fitting of X-ray diffraction (XRD) patterns, and 57Fe Mössbauer spectroscopy, we sought to follow the temporal evolution in Fe mineralogy and elucidate the fate of adsorbed 57Fe(II). At low C:Fe molar ratios (0-0.05), rapid oxidation of surface-adsorbed 57Fe(II) resulted in 57Fe-enriched crystalline minerals and nearly complete mineral transformation within days. With increasing OM content, the atom exchange between the added aqueous 57Fe(II) and Fe in the organic-rich solids still occurred; however, XRD analysis showed that crystalline mineral precipitation was strongly inhibited. For high OM-content materials (C:Fe ≥ 1.2), Mössbauer spectroscopy revealed up to 39% lepidocrocite in the final Fe(II)-reacted samples. Because lepidocrocite was not detectable by XRD, we suggest that the Mössbauer-detected lepidocrocite consisted of nanosized clusters with lepidocrocite-like local structure, similar to the lepidocrocite found in natural flocs. Collectively, our results demonstrate that the C content of ferrihydrite-OM coprecipitates strongly impacts the degree and pathways of Fe mineral transformations and iron atom exchange during reactions with aqueous Fe(II).

Bio‐inspired Oxidation of 1‐Aminocarboxylic Acids by a Nonheme Iron(II) Complex: Mimicking the Activity of 1‐Aminocyclopropane‐1‐carboxylic Acid Oxidase

Three new ternary iron(II) complexes, [(TpPh2)FeII(ACC)] (1), [(TpPh2)FeII(ACH)] (2), and [(TpPh2)FeII(ADP)] (3) [TpPh2 = hydrotris(3,5‐diphenylpyrazol‐1‐yl)borate, ACC‐H = 1‐aminocyclopropane‐1‐carboxylic acid, ACH‐H = 1‐aminocyclohexane‐1‐carboxylic acid, and ADP‐H = 2‐amino‐2,2‐diphenylacetic acid] were isolated and characterized. X‐ray crystal structures of 1 and 2 reveal that in both the complexes the TpPh2 ligand binds to the central iron atom in a facial mode, and the respective 1‐aminocarboxylate monoanion displays bidentate binding mode through one carboxylate oxygen and one amine nitrogen donor. Complex 1 represents a structural model of the enzyme‐substrate adduct of the enzyme, 1‐aminocyclopropane‐1‐carboxylic acid oxidase (ACCO). The iron(II) complexes react with O2 at ambient temperature to convert the metal coordinated coligands to the corresponding carbonyl compound but in low yields. The yields of the decarboxylated products, however, increase upon increasing the reaction temperature. Isotope labelling experiments and interception studies indicate that the reductive activation of O2 at the central iron atom concomitant with two‐electron oxidative decarboxylation of the coligand following a pathway very similar to that proposed for the iron(II)‐α‐hydroxy acid complexes of the TpPh2 ligand.

Tetraphenylphosphonium tetrakis(trimethylsilanolato)ferrate(III)

The structure of tetraphenylphosphonium tetrakis(trimethylsilanolato)ferrate(III), [(C6H5)4P][Fe(OSi(CH3)3)4], has tetragonal (I-4) symmetry, and was refined as an inversion twin. It is an ionic compound consisting of a tetraphenylphosphonium cation and a tetrakis(trimethylsilanolato)ferrate(III) anion. The crystal structure comprises the two ionic species each centered on a -4 symmetry element and contributing a fourth of its structure to the asymmetric unit. Each is surrounded by counter-ions on all sides. The cation contains a central phosphorous atom bound to four phenyl groups in a tetrahedral arrangement, while the anion contains a central iron(III) atom tetrahedrally coordinated by four trimethylsilanolato ligands.

The self-template synthesis of highly efficient hollow structure Fe/N/C electrocatalysts with Fe-N coordination for the oxygen reduction reaction.

The exploration of highly efficient catalysts to replace noble metal platinum for the oxygen reduction reaction, on which M/N/C catalysts have shed brilliant light, is greatly significant but challenging. This paper presents a strategy for synthesizing highly efficient and stabilized hollow structure Fe/N/C catalysts with iron and nitrogen doped into the carbon layer by the self-template method. The prepared Fe/N/C catalysts with NaCl protection during pyrolysis are characterized by a unique hollow structure, porous morphology and Fe–N coordination as the active sites, all of which significantly endow the materials with excellent properties towards the ORR, including high electrical conductivity, long-term durability and outstanding capacity for methanol tolerance. We employed X-ray absorption fine structure spectrometry to investigate the chemical state and coordination environment of the central iron atoms of the Fe/N/C catalysts, which also clarified the promoting effect of the NaCl protection for Fe–N coordination during pyrolysis. In particular, the Fe/N/C catalysts exhibit positive half-wave potentials (0.84 V vs. RHE) and Tafel slope comparable to 20% commercial Pt/C, possessing four-electron transfer pathway as well as excellent long-term stability and methanol tolerance in alkaline medium.

Role of Iron(III)-salen Chloride as Oxidizing Agent with Thiodiglycolic Acid: The Effect of Axial Ligands

The sulfoxidation of thiodiglycolic acid with iron(III)-salen chloride, which acts as an oxidizing agent without any terminal oxidant, in 50% aqueous acetonitrile medium has been studied. A substantial red shift in the λmaxvalue of FeIII-salen was observed in aqueous medium. The spectrophotometric kinetic study indicates that [FeIII(salen)]+ is the active oxidizing species and the reaction follows Michaelis-Menten kinetics with respect to the substrate. The rate of the reaction is highly sensitive to the medium. A reaction mechanism involving electron transfer from sulfur atom of thiodiglycolic acid to the central iron atom of [FeIII(salen)]+ is proposed. The presence of nitrogenous bases like pyridine, imidazole and 1-methylimidazole shows a retarding effect on the reaction rate. This can be explained on the basis of binding of these ligands to the coordination sphere of [FeIII(salen)]+ prior to the reaction with the substrate. The observed order of reactivity, pyridine > 1-methylimidazole > imidazole, is in accordance with the inverse of π-donating ability of nitrogen bases.

Dual-electrospray synthesis: A method of studying unique coordination complexes in the gas phase

Tris(2,2′-bipyridine)ruthenium(II) and similar complexes containing the 1,10-phenanthroline ligand were formed by spraying a ligand solution and a ruthenium trichloride solution through two independent electrospray (ESI) emitters. This was confirmed by comparing ion mobility drift time, mass spectra, and energy-resolved collision-induced dissociation (CID) breakdown curves with the corresponding reference standards. The complexes of 2,2′-bipyridine and 1,10-phenantroline with iron(II), and their mixed-ligand complexes formed by dual-spray exhibited two additional hydrogen atoms. By CID, these unique gas phase complexes showed similar initial ligand loss to the reference standards, however the sequential ligand loss showed unique dissociation channels and energetics. Density functional theory calculations of the [Fe(phen)3+2H]2+ complex and its fragment ions suggest that, after the initial loss of one ligand, the additional hydrogen atoms transfer to the central iron atom. The relative energy of the dissociation channels showed good agreement with experimental breakdown curves.

Oxygen Atom Transfer Using an Iron(IV)-Oxo Embedded in a Tetracyclic N-Heterocyclic Carbene System: How Does the Reactivity Compare to Cytochrome P450 Compound I?

N-Heterocyclic carbenes (NHC) are commonly featured as ligands in transition metal catalysis. Recently, a cyclic system containing four NHC groups with a central iron atom was synthesized and its iron(IV)-oxo species, [FeIV (O)(cNHC4 )]2+ , was characterized. This tetracyclic NHC ligand system may give the iron(IV)-oxo species unique catalytic properties as compared to traditional non-heme and heme iron ligand systems. Therefore, we performed a computational study on the structure and reactivity of the [FeIV (O)(cNHC4 )]2+ complex in substrate hydroxylation and epoxidation reactions. The reactivity patterns are compared with cytochrome P450 Compound I and non-heme iron(IV)-oxo models and it is shown that the [FeIV (O)(cNHC4 )]2+ system is an effective oxidant with oxidative power analogous to P450 Compound I. Unfortunately, in polar solvents, a solvent molecule will bind to the sixth ligand position and decrease the catalytic activity of the oxidant. A molecular orbital and valence bond analysis provides insight into the origin of the reactivity differences and makes predictions of how to further exploit these systems in chemical catalysis.

Magnetic coupling and relaxation in Fe[N(SiPh2Me)2]2 molecular magnet

In Fe[N(SiPh2Me)2]2 molecular magnet, an extraordinary B ≈ 92 T hyperfine field was found in the 5 K 57Fe Mossbauer spectrum under an external magnetic field of 0.1 T. This evidences the presence of an unquenched orbital angular moment at the central iron atom. Fe[N(SiPh2Me)2]2 complex is thus shown to represent a further example of low-coordinate iron complexes where quasi free-ion magnetism visualizes itself through an unquenched orbital moment. Magnetization measurements and hysteresis in magnetization indicated exchange coupling and nanosized magnetic units.

A Family of Chiral Ferrocenyl Diols: Modular Synthesis, Solid-State Characterization, and Application in Asymmetric Organocatalysis.

Readily available chiral diol scaffolds are useful as sources of chirality for asymmetric synthesis, however, few such scaffolds are readily available in enantiopure form. Reported herein is a cheap and modular synthesis of a novel family of chiral ferrocenyl diols in excellent yields with excellent enantio- and diastereoselectivity (>99 % ee and 99 % de). These diols possess not only planar and central chirality, but also axial chirality around the central iron atom. Characterization of these diols by X-ray crystallography revealed intra- and intermolecular hydrogen-bond networks depending on substitution at the carbinol positions. The potential of these diols as catalysts was subsequently demonstrated in an asymmetric hetero-Diels-Alder reaction which provided cycloadducts in up to 84 % yield with ee values ranging from -92 to +72 %.

A Family of Chiral Ferrocenyl Diols: Modular Synthesis, Solid‐State Characterization, and Application in Asymmetric Organocatalysis

AbstractReadily available chiral diol scaffolds are useful as sources of chirality for asymmetric synthesis, however, few such scaffolds are readily available in enantiopure form. Reported herein is a cheap and modular synthesis of a novel family of chiral ferrocenyl diols in excellent yields with excellent enantio‐ and diastereoselectivity (>99 % ee and 99 % de). These diols possess not only planar and central chirality, but also axial chirality around the central iron atom. Characterization of these diols by X‐ray crystallography revealed intra‐ and intermolecular hydrogen‐bond networks depending on substitution at the carbinol positions. The potential of these diols as catalysts was subsequently demonstrated in an asymmetric hetero‐Diels–Alder reaction which provided cycloadducts in up to 84 % yield with ee values ranging from −92 to +72 %.

Inner-Shell Water Rearrangement Following Photoexcitation of Tris(2,2'-bipyridine)iron(II).

The solvent dynamics in Fe-tris-bipyridine [Fe(bpy)3](2+) upon electronic excitation (oxidation) and subsequent relaxation is followed on the picosecond time scale by using atomistic simulations. Starting from the low spin (LS) Fe(II)LS state the transition to the excited Fe(III) (1,3)MLCT (metal-to-ligand charge transfer) state decreases the water coordination in immediate proximity of the central iron atom. This readjustment of the solvent shell occurs on the subpicosecond time scale. Full relaxation of the water environment would occur on the 10 ps time scale which is, however, never reached as the lifetime of the (1,3)MLCT state is only 200 fs. Further relaxation toward the long-lived (665 ps) [Fe(II)HS(bpy)3] high spin (HS) state does not change the degree of solvation. The results support a model in which the change in the degree of solvation is driven by electronic effects (charge redistribution) and not by structural changes (change in bond lengths). Furthermore, the results are consistent with recent combined X-ray emission (XES) and X-ray diffusion (XDS) scattering experiments which provided evidence for a reduced solvent density upon excitation of the [Fe(II)LS(bpy)3] initial state. However, the time scale for water exchange dynamics is faster than that found in the experiments.

Iron Atom Exchange between Hematite and Aqueous Fe(II).

Aqueous Fe(II) has been shown to exchange with structural Fe(III) in goethite without any significant phase transformation. It remains unclear, however, whether aqueous Fe(II) undergoes similar exchange reactions with structural Fe(III) in hematite, a ubiquitous iron oxide mineral. Here, we use an enriched (57)Fe tracer to show that aqueous Fe(II) exchanges with structural Fe(III) in hematite at room temperature, and that the amount of exchange is influenced by particle size, pH, and Fe(II) concentration. Reaction of 80 nm-hematite (27 m(2) g(-1)) with aqueous Fe(II) at pH 7.0 for 30 days results in ∼5% of its structural Fe(III) atoms exchanging with Fe(II) in solution, which equates to about one surface iron layer. Smaller, 50 nm-hematite particles (54 m(2) g(-1)) undergo about 25% exchange (∼3× surface iron) with aqueous Fe(II), demonstrating that structural Fe(III) in hematite is accessible to the fluid in the presence of Fe(II). The extent of exchange in hematite increases with pH up to 7.5 and then begins to decrease as the pH progresses to 8.0, likely due to surface site saturation by sorbed Fe(II). Similarly, when we vary the initial amount of added Fe(II), we observe decreasing amounts of exchange when aqueous Fe(II) is increased beyond surface saturation. This work shows that Fe(II) can catalyze iron atom exchange between bulk hematite and aqueous Fe(II), despite hematite being the most thermodynamically stable iron oxide.

Peroxidative permeabilization of liposomes induced by cytochrome c/cardiolipin complex

Interaction of cytochrome c with mitochondrial cardiolipin converting this electron transfer protein into peroxidase is accepted to play an essential role in apoptosis. Cytochrome c/cardiolipin peroxidase activity was found here to cause leakage of carboxyfluorescein, sulforhodamine B and 3-kDa (but not 10-kDa) fluorescent dextran from liposomes. A marked decrease in the amplitude of the autocorrelation function was detected with a fluorescence correlation spectroscopy setup upon incubation of dye-loaded cardiolipin-containing liposomes with cytochrome c and H2O2, thereby showing release of fluorescent markers from liposomes. The cytochrome c/H2O2-induced liposome leakage was suppressed upon increasing the ionic strength, in contrast to the leakage provoked by Fe/ascorbate, suggesting that the binding of cyt c to negatively-charged membranes was required for the permeabilization process. The cyt c/H2O2-induced liposome leakage was abolished by cyanide presumably competing with H2O2 for coordination with the central iron atom of the heme in cyt c. The cytochrome c/H2O2 permeabilization activity was substantially diminished by antioxidants (trolox, butylhydroxytoluene and quercetin) and was precluded if fully saturated tetramyristoyl-cardiolipin was substituted for bovine heart cardiolipin. These data favor the involvement of oxidized cardiolipin molecules in membrane permeabilization resulting from cytochrome c/cardiolipin peroxidase activity. In agreement with previous observations, high concentrations of cyt c induced liposome leakage in the absence of H2O2, however this process was not sensitive to antioxidants and cyanide suggesting direct membrane poration by the protein without the involvement of lipid peroxidation.

DFT study of the oxygen reduction reaction on iron, cobalt and manganese macrocycle active sites

The best performing non-precious metal based catalysts for polymer electrolyte membrane fuel cells are manufactured by incorporation of nitrogen into a carbon structure in the presence of iron and cobalt. Herein, density functional theory (DFT) calculations have been performed to investigate the oxygen reduction reaction on catalyst active sites modelled as transition metal macrocycles with iron, cobalt or manganese central atoms. The effects of the transition metal and macrocycle structure have been investigated. The structure of the most promising active sites has been proposed, and the detailed potential energy profiles of the oxygen reduction reaction have been obtained over the active sites, including all intermediate steps with corresponding activation barriers. The efficiency of the active sites depends primarily on the transition metal nature, and the central iron atom accounts for the higher catalytic activity than cobalt and manganese. The central manganese atom can favour the two-electron oxygen reduction pathway and thus yielding hydrogen peroxide.

Fe2+ catalyzed iron atom exchange and re-crystallization in a tropical soil

Aqueous ferrous iron (Fe2+(aq)) is known to transfer electrons and exchange structural positions with solid-phase ferric (FeIII) atoms in many Fe minerals. However, this process has not been demonstrated in soils or sediments. In a 28-day sterile experiment, we reacted 57Fe-enriched Fe2+(aq) (57/54Fe=5.884±0.003) with a tropical soil (natural abundance 57/54Fe=0.363±0.004) under anoxic conditions and tracked 57/54Fe in the aqueous phase and in sequential 0.5M and 7M HCl extractions targeting surface-adsorbed and bulk-soil Fe, respectively; we also analyzed the reacted soil with 57Fe Mössbauer spectroscopy. In 28days, the aqueous and bulk pools both moved ∼7% toward the isotopic equilibrium (57/54Fe=1.33). Using a kinetic model, we calculate final adsorption-corrected 57/54Fe ratios of 5.56±0.05 and 0.43±0.03 in the aqueous and bulk pools, respectively. The aqueous and surface/labile Fe initially exchanged atoms rapidly (10–80mmolkg−1d−1) decreasing to a near constant rate of 1mmolkg−1d−1 that was close to the 0.74mmolkg−1d−1 exchange-rate between the surface and bulk pools. Thus, after 28 days we calculate aqueous Fe has exchanged with 20.1mmolkg−1 of bulk Fe atoms (1.9% of total Fe) in addition to the 17.0mmolkg−1 of surface/labile Fe atoms (1.6% of total Fe), which have likely turned over several times during our experiment. Extrapolating these rates, we calculate a hypothetical whole-soil turnover time of ∼3.6yrs. Furthermore, Mössbauer spectroscopy indicates the soil-incorporated 57Fe label re-crystallized as short-range-ordered (SRO) FeIII-oxyhydroxides: our model suggests this pool could turnover in less than seven months via Fe2+-catalyzed recrystallization. Thus, we conclude Fe atom exchange can occur in soils at rates fast enough to impact ecological processes reliant on Fe minerals, but sufficiently slow that complete Fe mineral turnover is unlikely, except perhaps in permanently anoxic environments.

Assessing Catalytic Activities Through Modeling Net Charges of Iron Complex Precatalysts

The potential activities for two series of iron complex precatalysts on ethylene reactivity are evaluated by the density functional theory (DFT)–charge equilibration (DFT–QEq) method on the basis of the molecular mechanics (MM–QEq) method. All three spin states on the central iron atom are calculated through the two charge methods to obtain the effective net charge, in addition to the QEq method alone. The results show that reasonable charge values are obtained by the QEq method, well reflecting the influence of substituents and revealing correlations between the activity and the effective net charge. All these series of iron complex precatalysts present the same tendency: the potential activities are elevated along with a decreasing effective net charge on the iron atom. Relying on the electronic influence of substituents on the ligands, the variation trends are grouped into two classes, which present the same correlation. image

Renormalization of myoglobin–ligand binding energetics by quantum many-body effects

We carry out a first-principles atomistic study of the electronic mechanisms of ligand binding and discrimination in the myoglobin protein. Electronic correlation effects are taken into account using one of the most advanced methods currently available, namely a linear-scaling density functional theory (DFT) approach wherein the treatment of localized iron 3d electrons is further refined using dynamical mean-field theory. This combination of methods explicitly accounts for dynamical and multireference quantum physics, such as valence and spin fluctuations, of the 3d electrons, while treating a significant proportion of the protein (more than 1,000 atoms) with DFT. The computed electronic structure of the myoglobin complexes and the nature of the Fe-O2 bonding are validated against experimental spectroscopic observables. We elucidate and solve a long-standing problem related to the quantum-mechanical description of the respiration process, namely that DFT calculations predict a strong imbalance between O2 and CO binding, favoring the latter to an unphysically large extent. We show that the explicit inclusion of the many-body effects induced by the Hund's coupling mechanism results in the correct prediction of similar binding energies for oxy- and carbonmonoxymyoglobin.