RESUMEN
Halogenation of aliphatic C-H bonds is a chemical transformation performed in nature by mononuclear nonheme iron dependent halogenases. The mechanism involves the formation of an iron(IV)-oxo-chloride species that abstracts the hydrogen atom from the reactive C-H bond to form a carbon-centered radical that selectively reacts with the bound chloride ligand, a process commonly referred to as halide rebound. The factors that determine the halide rebound, as opposed to the reaction with the incipient hydroxide ligand, are not clearly understood and examples of well-defined iron(IV)-oxo-halide compounds competent in C-H halogenation are scarce. In this work we have studied the reactivity of three well-defined iron(IV)-oxo complexes containing variants of the tetradentate 1-(2-pyridylmethyl)-1,4,7-triazacyclononane ligand (Pytacn). Interestingly, these compounds exhibit a change in their chemoselectivity towards the functionalization of C-H bonds under certain conditions: their reaction towards C-H bonds in the presence of a halide anionleads to exclusive oxygenation, while the addition of a superacid results in halogenation. Almost quantitative halogenation of ethylbenzene is observed when using the two systems with more sterically congested ligands and even the chlorination of strong C-H bonds such as those of cyclohexane is performed when a methyl group is present in the sixth position of the pyridine ring of the ligand. Mechanistic studies suggest that both reactions, oxygenation and halogenation, proceed through a common rate determining hydrogen atom transfer step and the presence of the acid dictates the fate of the resulting alkyl radical towards preferential halogenation over oxygenation.
Asunto(s)
Halogenación , Hierro , Protones , Hierro/química , Complejos de Coordinación/química , Ligandos , Carbono/química , Oxígeno/químicaRESUMEN
Iron-sulfur (Fe-S) clusters are essential inorganic cofactors dedicated to a wide range of biological functions, including electron transfer and catalysis. Specialized multiprotein machineries present in all types of organisms support their biosynthesis. These machineries encompass a scaffold protein, on which Fe-S clusters are assembled before being transferred to cellular targets. Here, we describe the first characterization of the native Fe-S cluster of the anaerobically purified SufBC2D scaffold from Escherichia coli by XAS and Mössbauer, UV-visible absorption, and EPR spectroscopies. Interestingly, we propose that SufBC2D harbors two iron-sulfur-containing species, a [2Fe-2S] cluster and an as-yet unidentified species. Mutagenesis and biochemistry were used to propose amino acid ligands for the [2Fe-2S] cluster, supporting the hypothesis that both SufB and SufD are involved in the Fe-S cluster ligation. The [2Fe-2S] cluster can be transferred to ferredoxin in agreement with the SufBC2D scaffold function. These results are discussed in the context of Fe-S cluster biogenesis.
Asunto(s)
Proteínas de Escherichia coli , Escherichia coli , Proteínas Hierro-Azufre , Proteínas Hierro-Azufre/química , Proteínas Hierro-Azufre/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Espectroscopía de Resonancia por Spin del Electrón , Espectroscopía de Mossbauer , Espectroscopía de Absorción de Rayos X , Proteínas PortadorasRESUMEN
Human mitoNEET (mNT) and CISD2 are two NEET proteins characterized by an atypical [2Fe-2S] cluster coordination involving three cysteines and one histidine. They act as redox switches with an active state linked to the oxidation of their cluster. In the present study, we show that reduced glutathione but also free thiol-containing molecules such as ß-mercaptoethanol can induce a loss of the mNT cluster under aerobic conditions, while CISD2 cluster appears more resistant. This disassembly occurs through a radical-based mechanism as previously observed with the bacterial SoxR. Interestingly, adding cysteine prevents glutathione-induced cluster loss. At low pH, glutathione can bind mNT in the vicinity of the cluster. These results suggest a potential new regulation mechanism of mNT activity by glutathione, an essential actor of the intracellular redox state.
Asunto(s)
Proteínas Mitocondriales , Humanos , Cisteína/metabolismo , Glutatión/metabolismo , Homeostasis , Proteínas Mitocondriales/química , Proteínas Mitocondriales/metabolismo , Oxidación-Reducción , Compuestos de SulfhidriloRESUMEN
Dinuclear transition metal complexes with direct metal-metal interactions have the potential to generate unique reactivities and properties. Using asymmetric triazine ligands HN3tBuR (R = Et, iPr, nBu) featuring different alkyl substituents at 1,3-N centers, we report here the first rational synthesis of 'tetragonal lantern' type Fe(II) triazenides [Fe2(N3tBuR)4] [R = Et (1), iPr (2), nBu (3)] having an exceptionally short Fe-Fe distance (2.167-2.174 Å). Unlike the previously reported lantern structures with related amidinate or guanidinate ligands, highly air-sensitive 1-3 show a lower spin ground state, as indicated by Mössbauer, 1H NMR and DFT studies.
RESUMEN
Nitrene transfer reactions catalyzed by heme proteins have broad potential for the stereoselective formation of carbon-nitrogen bonds. However, competition between productive nitrene transfer and the undesirable reduction of nitrene precursors limits the broad implementation of such biocatalytic methods. Here, we investigated the reduction of azides by the model heme protein myoglobin to gain mechanistic insights into the factors that control the fate of key reaction intermediates. In this system, the reaction proceeds via a proposed nitrene intermediate that is rapidly reduced and protonated to give a reactive ferrous amide species, which we characterized by UV/vis and Mössbauer spectroscopies, quantum mechanical calculations, and X-ray crystallography. Rate-limiting protonation of the ferrous amide to produce the corresponding amine is the final step in the catalytic cycle. These findings contribute to our understanding of the heme protein-catalyzed reduction of azides and provide a guide for future enzyme engineering campaigns to create more efficient nitrene transferases. Moreover, harnessing the reduction reaction in a chemoenzymatic cascade provided a potentially practical route to substituted pyrroles.
RESUMEN
We have discovered a protein with an amino acid composition exceptionally rich in glycine and cysteine residues in the giant virus mimivirus. This small 6 kDa protein is among the most abundant proteins in the icosahedral 0.75 µm viral particles; it has no predicted function but is probably essential for infection. The aerobically purified red-brownish protein overproduced inEscherichia coli contained both iron and inorganic sulfide. UV/vis, EPR, and Mössbauer studies revealed that the viral protein, coined GciS, accommodated two distinct Fe-S clusters: a diamagnetic S = 0 [2Fe-2S]2+ cluster and a paramagnetic S = 5/2 linear [3Fe-4S]1+ cluster, a geometry rarely stabilized in native proteins. Orthologs of mimivirus GciS were identified within all clades of Megavirinae, a Mimiviridae subfamily infecting Acanthamoeba, including the distantly related tupanviruses, and displayed the same spectroscopic features. Thus, these glycine/cysteine-rich proteins form a new family of viral Fe-S proteins sharing unique Fe-S cluster binding properties.
Asunto(s)
Virus Gigantes , Proteínas Hierro-Azufre , Proteínas Hierro-Azufre/química , Virus Gigantes/metabolismo , Cisteína/química , Glicina , Análisis Espectral , Espectroscopía de Resonancia por Spin del ElectrónRESUMEN
Nitrene transfer reactions have emerged as one of the most powerful and versatile ways to insert an amine function to various kinds of hydrocarbon substrates. However, the mechanisms of nitrene generation have not been studied in depth albeit their formation is taken for granted in most cases without definitive evidence of their occurrence. In the present work, we compare the generation of tosylimido iron species and NTs transfer from FeII and FeIII precursors where the metal is embedded in a tetracarbene macrocycle. Catalytic nitrene transfer to reference substrates (thioanisole, styrene, ethylbenzene and cyclohexane) revealed that the same active species was at play, irrespective of the ferrous versus ferric nature of the precursor. Through combination of spectroscopic (UV-visible, Mössbauer), ESI-MS and DFT studies, an FeIV tosylimido species was identified as the catalytically active species and was characterized spectroscopically and computationally. Whereas its formation from the FeII precursor was expected by a two-electron oxidative addition, its formation from an FeIII precursor was unprecedented. Thanks to a combination of spectroscopic (UV-visible, EPR, Hyscore and Mössbauer), ESI-MS and DFT studies, we found that, when starting from the FeIII precursor, an FeIII tosyliodinane adduct was formed and decomposed into an FeV tosylimido species which generated the catalytically active FeIV tosylimide through a comproportionation process with the FeIII precursor.
Asunto(s)
Compuestos Férricos , Hierro , Compuestos Férricos/química , Modelos Moleculares , Catálisis , Hierro/química , Compuestos Ferrosos/químicaRESUMEN
Synthetic iron-sulfur cubanes are models for biological cofactors, which are essential to delineate oxidation states in the more complex enzymatic systems. However, a complete series of [Fe4S4]n complexes spanning all redox states accessible by 1-electron transformations of the individual iron atoms (n = 0-4+) has never been prepared, deterring the methodical comparison of structure and spectroscopic signature. Here, we demonstrate that the use of a bulky arylthiolate ligand promoting the encapsulation of alkali-metal cations in the vicinity of the cubane enables the synthesis of such a series. Characterization by EPR, 57Fe Mössbauer spectroscopy, UV-visible electronic absorption, variable-temperature X-ray diffraction analysis, and cyclic voltammetry reveals key trends for the geometry of the Fe4S4 core as well as for the Mössbauer isomer shift, which both correlate systematically with oxidation state. Furthermore, we confirm the S = 4 electronic ground state of the most reduced member of the series, [Fe4S4]0, and provide electrochemical evidence that it is accessible within 0.82 V from the [Fe4S4]2+ state, highlighting its relevance as a mimic of the nitrogenase iron protein cluster.
Asunto(s)
Materiales Biomiméticos , Coenzimas , Hidrocarburos , Hierro , Nitrogenasa , Azufre , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/química , Coenzimas/síntesis química , Coenzimas/química , Hidrocarburos/síntesis química , Hidrocarburos/química , Hierro/química , Nitrogenasa/química , Oxidación-Reducción , Azufre/químicaRESUMEN
The ruthenium nitrosyl moiety, {RuNO}6, is important as a potential releasing agent of nitric oxide and is of inherent interest in coordination chemistry. Typically, {RuNO}6 is found in mononuclear complexes. Herein we describe the synthesis and characterization of several multimetal cluster complexes that contain this unit. Specifically, the heterotrinuclear µ3-oxido clusters [Fe2RuCl4(µ3-O)(µ-OMe)(µ-pz)2(NO)(Hpz)2] (6) and [Fe2RuCl3(µ3-O)(µ-OMe)(µ-pz)3(MeOH)(NO)(Hpz)][Fe2RuCl3(µ3-O)(µ-OMe)(µ-pz)3(DMF)(NO)(Hpz)] (7·MeOH·2H2O) and the heterotetranuclear µ4-oxido complex [Ga3RuCl3(µ4-O)(µ-OMe)3(µ-pz)4(NO)] (8) were prepared from trans-[Ru(OH)(NO)(Hpz)4]Cl2 (5), which itself was prepared via acidic hydrolysis of the linear heterotrinuclear complex {[Ru(µ-OH)(µ-pz)2(pz)(NO)(Hpz)]2Mg} (4). Complex 4 was synthesized from the mononuclear Ru complexes (H2pz)[trans-RuCl4(Hpz)2] (1), trans-[RuCl2(Hpz)4]Cl (2), and trans-[RuCl2(Hpz)4] (3). The new compounds 4-8 were all characterized by elemental analysis, ESI mass spectrometry, IR, UV-vis, and 1H NMR spectroscopy, and single-crystal X-ray diffraction, with complexes 6 and 7 being characterized also by temperature-dependent magnetic susceptibility measurements and Mössbauer spectroscopy. Magnetometry indicated a strong antiferromagnetic interaction between paramagnetic centers in 6 and 7. The ability of 4 and 6-8 to form linkage isomers and release NO upon irradiation in the solid state was investigated by IR spectroscopy. A theoretical investigation of the electronic structure of 6 by DFT and ab initio CASSCF/NEVPT2 calculations indicated a redox-noninnocent behavior of the NO ancillary ligand in 6, which was also manifested in TD-DFT calculations of its electronic absorption spectrum. The electronic structure of 6 was also studied by an X-ray charge density analysis.
RESUMEN
In the context of bioinspired OAT catalysis, we developed a tetradentate dipyrrinpyridine ligand, a hybrid of hemic and non-hemic models. The catalytic activity of the iron(III) derivative was investigated in the presence of iodosylbenzene. Unexpectedly, MS, EPR, Mössbauer, UV-visible and FTIR spectroscopic signatures supported by DFT calculations provide convincing evidence for the involvement of a relevant FeIII-O-NPy active intermediate.
Asunto(s)
Compuestos Férricos/química , Oxígeno/química , Piridinas/química , Modelos Moleculares , Estructura MolecularRESUMEN
(Cyclopentadienone)iron carbonyl complexes have recently received particular attention for their use as catalysts in hydrogenation or transfer hydrogenation reactions including the N-alkylation of amines with alcohols. This is due to their easy synthesis from simple and cheap materials, air and water stabilities, and the crucial metal-ligand cooperation giving rise to unique catalytic properties. Here, we report a Mössbauer spectroscopic and computational investigation of such a complex and its corresponding activated species for dehydrogenation and hydrogenation reactions. This study affords a deeper understanding of the species formed by the reaction with Me3NO and their distribution upon the added amount of an oxidant.
RESUMEN
Human anamorsin is an iron-sulfur (Fe-S)-cluster-binding protein acting as an electron donor in the early steps of cytosolic iron-sulfur protein biogenesis. Human anamorsin belongs to the eukaryotic CIAPIN1 protein family and contains two highly conserved cysteine-rich motifs, each binding an Fe-S cluster. Inâ vitro works by various groups have provided rather controversial results for the type of Fe-S clusters bound to the CIAPIN1 proteins. In order to unravel the knot on this topic, we used an inâ cellulo approach combining Mössbauer and EPR spectroscopies to characterize the iron-sulfur-cluster-bound form of human anamorsin. We found that the protein binds two [2Fe-2S] clusters at both its cysteine-rich motifs.
Asunto(s)
Péptidos y Proteínas de Señalización Intracelular/química , Proteínas Hierro-Azufre/química , Espectroscopía de Resonancia por Spin del Electrón , Humanos , Unión Proteica , Espectroscopía de MossbauerRESUMEN
Both O2 and H2 O2 can oxidize iron at the ferroxidase center (FC) of Escherichia coli bacterioferritin (EcBfr) but mechanistic details of the two reactions need clarification. UV/Vis, EPR, and Mössbauer spectroscopies have been used to follow the reactions when apo-EcBfr, pre-loaded anaerobically with Fe2+ , was exposed to O2 or H2 O2 . We show that O2 binds di-Fe2+ FC reversibly, two Fe2+ ions are oxidized in concert and a H2 O2 molecule is formed and released to the solution. This peroxide molecule further oxidizes another di-Fe2+ FC, at a rate circa 1000 faster than O2 , ensuring an overall 1:4 stoichiometry of iron oxidation by O2 . Initially formed Fe3+ can further react with H2 O2 (producing protein bound radicals) but relaxes within seconds to an H2 O2 -unreactive di-Fe3+ form. The data obtained suggest that the primary role of EcBfr in vivo may be to detoxify H2 O2 rather than sequester iron.
Asunto(s)
Proteínas Bacterianas/metabolismo , Ceruloplasmina/metabolismo , Grupo Citocromo b/metabolismo , Escherichia coli/química , Ferritinas/metabolismo , Peróxido de Hidrógeno/metabolismo , Hierro/metabolismo , Oxígeno/metabolismo , Proteínas Bacterianas/química , Ceruloplasmina/química , Grupo Citocromo b/química , Escherichia coli/metabolismo , Ferritinas/química , Peróxido de Hidrógeno/química , Hierro/química , Modelos Moleculares , Oxidación-Reducción , Oxígeno/químicaRESUMEN
Oxoiron(IV) complexes bearing tetradentate ligands have been extensively studied as models for the active oxidants in non-heme iron-dependent enzymes. These species are commonly generated by oxidation of their ferrous precursors. The mechanisms of these reactions have seldom been investigated. In this work, the reaction kinetics of complexes [FeII (CH3 CN)2 L](SbF6 )2 ([1](SbF6 )2 and [2](SbF6 )2 ) and [FeII (CF3 SO3 )2 L] ([1](OTf)2 and [2](OTf)2 (1, L=Me,H Pytacn; 2, L=nP,H Pytacn; R,R' Pytacn=1-[(6-R'-2-pyridyl)methyl]-4,7- di-R-1,4,7-triazacyclononane) with Bu4 NIO4 to form the corresponding [FeIV (O)(CH3 CN)L]2+ (3, L=Me,H Pytacn; 4, L=nP,H Pytacn) species was studied in acetonitrile/acetone at low temperatures. The reactions occur in a single kinetic step with activation parameters independent of the nature of the anion and similar to those obtained for the substitution reaction with Cl- as entering ligand, which indicates that formation of [FeIV (O)(CH3 CN)L]2+ is kinetically controlled by substitution in the starting complex to form [FeII (IO4 )(CH3 CN)L]+ intermediates that are converted rapidly to oxo complexes 3 and 4. The kinetics of the reaction is strongly dependent on the spin state of the starting complex. A detailed analysis of the magnetic susceptibility and kinetic data for the triflate complexes reveals that the experimental values of the activation parameters for both complexes are the result of partial compensation of the contributions from the thermodynamic parameters for the spin-crossover equilibrium and the activation parameters for substitution. The observation of these opposite and compensating effects by modifying the steric hindrance at the ligand illustrates so far unconsidered factors governing the mechanism of oxygen atom transfer leading to high-valent iron oxo species.
RESUMEN
Both O2 and H2O2 can oxidize iron at the ferroxidase center (FC) of Escherichia coli bacterioferritin (EcBfr) but mechanistic details of the two reactions need clarification. UV/Vis, EPR, and Mössbauer spectroscopies have been used to follow the reactions when apo-EcBfr, pre-loaded anaerobically with Fe2+, was exposed to O2 or H2O2. We show that O2 binds di-Fe2+ FC reversibly, two Fe2+ ions are oxidized in concert and a H2O2 molecule is formed and released to the solution. This peroxide molecule further oxidizes another di-Fe2+ FC, at a rate circa 1000 faster than O2, ensuring an overall 1:4 stoichiometry of iron oxidation by O2. Initially formed Fe3+ can further react with H2O2 (producing protein bound radicals) but relaxes within seconds to an H2O2-unreactive di-Fe3+ form. The data obtained suggest that the primary role of EcBfr in vivo may be to detoxify H2O2 rather than sequester iron.
RESUMEN
Two new symmetrical and unsymmetrical diiron(iii) complexes were synthesized and characterized by X-ray diffraction analysis, mass spectrometry, UV-visible and Mössbauer spectroscopies. They proved to be good catalysts for alkene and alkane oxidation reactions by H2O2 in acetonitrile solution, and interesting effects of both the nature and the symmetry of the complexes were observed on catalysis in the presence of water.
RESUMEN
A mononuclear iron(III) porphyrin compound exhibiting unexpectedly slow magnetic relaxation, which is a characteristic of single-ion magnet behaviour, is reported. This behaviour originates from the close proximity (≈550â cm-1 ) of the intermediate-spin S=3/2 excited states to the high-spin S=5/2 ground state. More quantitatively, although the ground state is mostly S=5/2, a spin-admixture model evidences a sizable contribution (≈15 %) of S=3/2 to the ground state, which as a consequence experiences large and positive axial anisotropy (D=+19.2â cm-1 ). Frequency-domain EPR spectroscopy allowed the mS = |±1/2⟩â|±3/2⟩ transitions to be directly accessed, and thus the very large zero-field splitting in this 3d5 system to be unambiguously measured. Other experimental results including magnetisation, Mössbauer, and field-domain EPR studies are consistent with this model, which is also supported by theoretical calculations.
RESUMEN
The electronic structure of three single-atom bridged diiron octapropylporphyrazine complexes (FePzPr8)2X having Fe(III)-O-Fe(III), Fe(III)-N-Fe(IV) and Fe(IV)-C-Fe(IV) structural units was investigated by Mössbauer spectroscopy and density functional theory (DFT) calculations. In this series, the isomer shift values decrease, whereas the values of quadrupole splitting become progressively greater indicating the increase of covalency of Fe-X bond in the µ-oxo, µ-nitrido, µ-carbido row. The Mössbauer data point to low-spin systems for the three complexes, and calculated data with B3LYP-D3 show a singlet state for µ-oxo and µ-carbido and a doublet state for µ-nitrido complexes. An excellent agreement was obtained between B3LYP-D3 optimized geometries and X-ray structural data. Among (FePzPr8)2X complexes, µ-oxo diiron species showed a higher reactivity in the cyclopropanation of styrene by ethyl diazoacetate to afford a 95% product yield with 0.1 mol % catalyst loading. A detailed DFT study allowed to get insight into electronic structure of binuclear carbene species and to confirm their involvement into carbene transfer reactions.
RESUMEN
Ate-iron(II) species such as [Ar3 FeII ]- (Ar=aryl) are key intermediates in Fe-catalyzed couplings between aryl nucleophiles and organic electrophiles. They can be active species in the catalytic cycle, or lead to Fe0 and FeI oxidation states, which can themselves be catalytically active or lead to unwished organic byproducts. Analysis of the reactivity of the intermediates obtained by step-by-step displacement of the mesityl groups in high-spin [Mes3 FeII ]- by less hindered phenyl ligands was performed, and uncovered the crucial role of both steric and electronic parameters in the formation of the Fe0 and FeI oxidation states. The formation of quaternized [Ar4 FeII MgBr(THF)]- intermediates allows the bielectronic reductive elimination energy required for the formation of Fe0 to be reduced. Similarly, the small steric pressure of the aryl groups in [Ar3 FeII ]- enables the formation of aryl-bridged [{FeII (Ar)2 }2 (µ-Ar)2 ]2- species, which afford the FeI oxidation state by bimetallic reductive elimination. These results are supported by 1 Hâ NMR, EPR, and 57 Fe Mössbauer spectroscopies, as well as by DFT calculations.
RESUMEN
Quinolinate synthase (NadA) is a [4Fe-4S] cluster-containing enzyme involved in the formation of quinolinic acid, the precursor of the essential NAD coenzyme. Here, we report the synthesis and activity of derivatives of the first inhibitor of NadA. Using multidisciplinary approaches we have investigated their action mechanism and discovered additional specific inhibitors of this enzyme.