Dinuclear Iron Research Articles

Diiron monooxygenases in natural product biosynthesis.

Covering: up to 2017 The participation of non-heme dinuclear iron cluster-containing monooxygenases in natural product biosynthetic pathways has been recognized only recently. At present, two families have been discovered. The archetypal member of the first family, CmlA, catalyzes β-hydroxylation of l-p-aminophenylalanine (l-PAPA) covalently linked to the nonribosomal peptide synthetase (NRPS) CmlP, thereby effecting the first step in the biosynthesis of chloramphenicol by Streptomyces venezuelae. CmlA houses the diiron cluster in a metallo-β-lactamase protein fold instead of the 4-helix bundle fold of nearly every other diiron monooxygenase. CmlA couples O2 activation and substrate hydroxylation via a structural change caused by formation of the l-PAPA-loaded CmlP:CmlA complex. The other new diiron family is typified by two enzymes, AurF and CmlI, which catalyze conversion of aryl-amine substrates to aryl-nitro products with incorporation of oxygen from O2. AurF from Streptomyces thioluteus catalyzes the formation of p-nitrobenzoate from p-aminobenzoate as a precursor to the biostatic compound aureothin, whereas CmlI from S. venezuelae catalyzes the ultimate aryl-amine to aryl-nitro step in chloramphenicol biosynthesis. Both enzymes stabilize a novel type of peroxo-intermediate as the reactive species. The rare 6-electron N-oxygenation reactions of CmlI and AurF involve two progressively oxidized pathway intermediates. The enzymes optimize efficiency by utilizing one of the reaction pathway intermediates as an in situ reductant for the diiron cluster, while simultaneously generating the next pathway intermediate. For CmlI, this reduction allows mid-pathway regeneration of the peroxo intermediate required to complete the biosynthesis. CmlI ensures specificity by carrying out the multistep aryl-amine oxygenation without dissociating intermediate products.

Kinetic studies of the impact of thiocyanate moiety on the catalytic properties of Cu(II) and Fe(III) complexes of a new Mannich base

Four new metal complexes of a novel Mannich base 5-methyl-2-((4-(pyridin-2-yl)piperazin-1-yl)methyl)phenol (HL) have been prepared. The compounds were characterized by an array of analytical and spectroscopic methods including Nuclear Magnetic Resonance, Infra-red and UV–Visible spectroscopy. Compounds 1–4 behaved as effective catalysts towards the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to its corresponding quinone in the presence of molecular oxygen in DMF solution while compound 4 proved to be the best catalyst with a turnover rate of 17.93 ± 1.10 h−1 as other complexes showed lower rates of oxidation. Also with the exception of dinuclear iron complex (4); thiocyanate containing Cu(II) complex exhibited lower catecholase activity compared to the Cu(II) complex without it.

Synthesis, structures of mononuclear and dinuclear iron(II) complexes supported by non-symmetric guanidinate(amidinate) ligands

A new family of Fe(II) compounds, 1–3, have been prepared, which are derived from the non-symmetric lithium guanidinate Li(L1) [L1 = N(Ph)C(R)N(SiMe3)] (R = 1-piperidino) or the lithium amidinates Li(L2) [L2 = N(Ph)C(Ph)N(SiMe3)] or Li(L3) [L3 = N(2,6-iPr2C6H3)C(Ph)N(SiMe3)]. Treatment of Li(L1), Li(L2) or Li(L3) with anhydrous FeCl2 afforded [(L1)4Fe2] (1), [(L2)4Fe2] (2) or [{L3}2Fe] (3), respectively. The molecular structures of 1–3 were determined by an X-ray diffraction study.

Synthesis, structure, and magnetic properties of the trans-difluoro-bis-phenoxo-bridged iron(III) complex FeIII2(BBPA)2F2 (H2BBPA = N,N-bis(2-hydroxybenzyl)-N-(2-pyridylmethyl)amine)

The bis-phenoxo-bridged dinuclear iron(III) compound Fe2(BBPA)2F2 (H2BBPA = N,N-bis(2-hydroxybenzyl)-N-(2-pyridylmethyl)amine) was structurally and magnetically characterized. It has distorted octahedral iron(III) centers with each iron(III) site having two cis-Fe(BBPA)F fragments that are bridged by two μ-phenoxo oxygen atoms. The dinuclear compound has a singlet ground state and thermally populated S = 5 undecet excited state 114 cm−1 above the ground state as the magnetic susceptibility can be fit to the Van Vleck dimer equation (H = −2JSa·Sb) with g = 2.02, J/kB = −15 K (−10.4 cm−1), and a room temperature effective moment of 7.16 μB/FeIII2 in accord with weak antiferromagnetic coupling within the iron(III) dimer.

Nuclear inelastic scattering at the diiron center of ribonucleotide reductase from Escherichia coli

The enzyme ribonucleotide reductase R2 catalyzes an important step in the synthesis of the building blocks of DNA, and harbors a dinuclear iron center required for activity. Not only the iron valence states but also the protonation of the iron ligands govern the enzymatic activity of the enzyme. We have performed Nuclear Inelastic Scattering (NIS) experiments on the 57Fe reconstituted ribonucleotide reductase R2 subunit from Escherichia coli (Ec R2a). Accompanying Mossbauer spectroscopic investigations show that the partial density of vibrational states (pDOS) of the 57Fe reconstituted Ec R2a sample contained contributions from both 57Fe-Ec R2a protein as well as unspecifically bound 57Fe. Subtraction of a featureless pDOS as obtained from protein-coated iron oxide particles allowed modeling of the contribution of non-specifically bound iron and thus the pDOS of 57Fe-Ec R2a could be obtained. Quantum-mechanics/molecular-mechanics (QM/MM) calculations of the whole 57Fe-Ec R2a protein with variations of the cofactor protonation were performed in order to assign characteristic bands to their corresponding molecular vibrational modes.

Spectroscopy and DFT Calculations of a Flavo-diiron Enzyme Implicate New Diiron Site Structures.

Flavo-diiron proteins (FDPs) are non-heme iron containing enzymes that are widespread in anaerobic bacteria, archaea, and protozoa, serving as the terminal components to dioxygen and nitric oxide reductive scavenging pathways in these organisms. FDPs contain a dinuclear iron active site similar to that in hemerythrin, ribonucleotide reductase, and methane monooxygenase, all of which can bind NO and O2. However, only FDP competently turns over NO to N2O. Here, EPR and Mössbauer spectroscopies allow electronic characterization of the diferric and diferrous species of FDP. The exchange-coupling constant J (Hex = JS1·S2) was found to increase from +20 cm-1 to +32 cm-1 upon reduction of the diferric to the diferrous species, indicative of (1) at least one hydroxo bridge between the iron ions for both states and (2) a change to the diiron core structure upon reduction. In comparison to characterized diiron proteins and synthetic complexes, the experimental values were consistent with a dihydroxo bridged diferric core, which loses one hydroxo bridge upon reduction. DFT calculations of these structures gave values of J and Mössbauer parameters in agreement with experiment. Although the crystal structure shows a hydrogen bond between the iron bound aspartate and the bridging solvent molecule, the DFT calculations of structures consistent with the crystal structure gave calculated values of J incompatible with the spectroscopic results. We conclude that the crystal structure of the diferric state does not represent the frozen solution structure and that a mono-μ-hydroxo diferrous species is the catalytically functional state that reacts with NO and O2. The new EPR spectroscopic probe of the diferric state indicated that the diferric structure of FDP prior to and immediately after turnover with NO are flavin mononucleotide (FMN) dependent, implicating an additional proton transfer role for FMN in turnover of NO.

High-Temperature Wide Thermal Hysteresis of an Iron(II) Dinuclear Double Helicate

Two new dinuclear iron(II) complexes (1·PF6 and 1·AsF6) of the general formula [FeII2(L2C3)2](X)4·nH2O·mMeCN (X = PF6, n = m = 1.5 for 1·PF6 and X = AsF6, n = 3, m = 1 for 1·AsF6) have been prepared and structurally characterized, where L2C3 is a bis-1,2,3-triazolimine type Schiff-base ligand, 1,1′-[propane-1,3-diylbis(1H-1,2,3-triazole-1,4-diyl)]bis{N-[2-(pyridin-2-yl)ethyl]methanimine}. Single crystal X-ray structure analyses revealed that 1·PF6 and 1·AsF6 are isostructural. The complex-cation [FeII2(L2C3)2]4+ of both has the same dinuclear double helicate architecture, in which each iron(II) center has an N6 octahedral coordination environment. Neighboring helicates are connected by intermolecular π–π interactions to give a chiral one-dimensional (1D) structure, and cationic 1D chains with the opposite chirality exist in the crystal lattice to give a heterochiral crystal. Magnetic and differential scanning calorimetry (DSC) studies were performed only for 1·AsF6, since the thermal stability in a high-temperature spin crossover (SCO) region of 1·PF6 is poorer than that of 1·AsF6. 1·AsF6 shows an unsymmetrical hysteretic SCO between the low-spin–low-spin (LS–LS) and high-spin–high-spin (HS–HS) states at above room temperature. The critical temperatures of warming (Tc↑) and cooling (Tc↓) modes in the abrupt spin transition area are 485 and 401 K, respectively, indicating the occurrence of 84 K-wide thermal hysteresis in the first thermal cycle.

Dioxygen Activation: Potential Future Technical Applications in Reactive Bubbly Flows

AbstractA dinuclear iron complex reacts with dioxygen to form a peroxido complex which has the potential to be used in homogeneous catalysis for selective oxidation of organic substrates. Previously, this complex has been investigated in organic solvents that seem less likely to be used on a larger scale in chemical industry. Transferring the reaction from organic solvents to aqueous solutions is difficult; however, first results indicated that derivatives of this complex should lead to the formation of a reactive oxidant from air in water. So far, the complexes investigated do not fulfill the requirements for their usage in a reactive bubbly flow system, but results of this work are promising for future applications.

Supramolecular Metal Arraying in Porphyrin/Phthalocyanine Conjugates for Catalytic Applications

Recently, we reported synthesis of porphyrin/phthalocyanine conjugates linked by fourfold rotaxane. In the conjugate, a porphyrin and a phthalocyanine formed a heterodimer in a cofacial fashion (Fig. 1a). [1] The conjugate is a promising platform for supramolecular catalysts based on dinuclear porphyrinoid complexes, because various metal ions to be a functional center are able to be arrayed in the conjugate regioselectively to afford homo- and hetero-dinuclear centers in the conjugate. [2,3] Moreover, these arrays were expanded to hetero-trinuclear arrays (Fig. 1b). [3-6] In this paper, we will present regioselective metal arraying in the conjugate and the supramolecular catalytic functions (Fig. 2). One of the methods to prepare the hetero-dinuclear complexes was to use the difference of metalation rate between porphyrin and phthalocyanine. We found reaction conditions for porphyrin-selective Fe(II) or Ni(II) insertion and phthalocyanine-selective Mn(II) insertion. Subsequent metalation to another porphyrinoid in the conjugate gave a hetero-dinuclear complex. We used these multinuclear complexes in the conjugate as catalysts. The dinuclear iron complex exhibited good catalytic activity in electrochemical reduction of molecular oxygen to water. [7]

Oxygen Reduction to Water by a Cofacial Dimer of Iron(III)-Porphyrin and Iron(III)-Phthalocyanine Linked through a Highly Flexible Fourfold Rotaxane.

A μ-oxo-dinuclear iron complex of a supramolecular porphyrin-phthalocyanine conjugate was synthesized and its catalytic electrochemical oxygen reduction properties were investigated. In the conjugate, porphyrin and phthalocyanine units were connected to form a cofacial dimeric structure through a flexible fourfold rotaxane linkage, which was advantageous for accommodating small substrates between the iron centers. The conjugate showed efficient catalytic properties, at more positive potentials than those of other reported dinuclear porphyrinoid iron complexes, to selectively afford water through a four-electron reduction process.

Frontispiece: Dinuclear Iron(III) and Nickel(II) Complexes Containing N‐(2‐Pyridylmethyl)‐N′‐(2‐hydroxyethyl)ethylenediamine: Catalytic Oxidation and Magnetic Properties

Frontispiece: Dinuclear Iron(III) and Nickel(II) Complexes Containing <i>N‐(</i>2‐Pyridylmethyl)‐<i>N</i>′‐(2‐hydroxyethyl)ethylenediamine: Catalytic Oxidation and Magnetic Properties

Dinuclear Iron(III) and Nickel(II) Complexes Containing N-(2-Pyridylmethyl)-N'-(2-hydroxyethyl)ethylenediamine: Catalytic Oxidation and Magnetic Properties.

Dinuclear FeIII and NiII complexes, [(phenO)Fe(N3 )]2 (NO3 )2 (1) and [(phenOH)Ni(N3 )2 ]2 (2), were prepared by treating Fe(NO3 )3 ⋅9 H2 O and Ni(NO3 )2 ⋅6 H2 O in methanol, respectively, with phenOH (=N-(2-pyridylmethyl)-N'-(2-hydroxyethyl)ethylenediamine) and NaN3 ; both 1 and 2 were characterized by elemental analysis, IR spectroscopy, X-ray diffraction, and magnetic susceptibility measurements. Two ethoxo-bridged FeIII and two azido-bridged NiII were observed in 1 and 2, respectively; corresponding antiferromagnetic interaction via the bridged ethoxo groups and strong ferromagnetic coupling via the bridged end-on azido ligands within the dimeric unit were observed. Complex 1 did not exhibit any catalytic activity, while 2 exhibited excellent catalytic activities for the epoxidation of aliphatic, aromatic, and terminal olefins.

Recent Advances in Small Clusters and Polymetallic Assemblies Based on Transition Metals and Dithiocarboxylate Zwitterions Derived from N-Heterocyclic Carbenes

N-Heterocyclic carbenes (NHCs) react readily with carbon disulfide to form stable, crystalline, zwitterionic adducts. In this review, we outline the various strategies that were applied to synthesize transition metal clusters based on such NHC·CS2 ligands. We also briefly survey their most salient structural features and catalytic properties. Because this research field is still in its infancy, only a limited number of structures containing metals from Group 7 (Mn and Re) and 8 (Fe and Ru) have been described so far. Homo- and heterobimetallic manganese and rhenium carbonyl clusters with the generic formula [MM′(CO)6(μ-κ2-S,S′-κ3-S,C,S′-S2C·NHC)] (MM′ = Mn2, MnRe, or Re2) were most thoroughly investigated. Isolated examples of dinuclear iron and tetranuclear ruthenium compounds, in which the dithiocarboxylate unit underwent fragmentation, were also reported. Other related polymetallic entities recently elaborated through the use of azolium-2-dithiocarboxylate zwitterions and Group 11 metals (Cu and Au) include copper-based coordination polymers, gold nanoparticles, and self-assembled monolayers.

Dioxygen Reactivity of an Iron Complex of 2-Aminophenol-Appended Ligand: Crystallographic Evidence of the Aromatic Ring Cleavage Product of the 2-Aminophenol Unit.

2-Aminophenol appended pentadentate ligand H2GanAP was synthesized by mixing equimolar amounts of 2-[bis(2-pyridylmethyl)aminomethyl]aniline (A) and 3,5-di-tert-butyl catechol in hexane in the presence of Et3N under air. The ligand reacted with Fe(ClO4)2·6H2O or Fe(ClO4)3·6H2O in the presence of tetrabutylammonium perchlorate, and Et3N under air and provided a μ2 oxo-bridged dinuclear iron complex (1). X-ray single-crystal analysis of complex 1 revealed the presence of a furan derivative, resulting from the oxidative aromatic C-C bond cleavage product of 2-aminophenol derivative, in the coordination sphere of each iron center. Mechanistic investigation for the formation of complex 1 established that in the absence of molecular oxygen no oxidation of the appended 2-amidophenolate unit took place. An iron(III)-amidophenolate complex, formed initially, further reacted with molecular oxygen and caused oxidative aromatic C-C bond cleavage via a putative alkylperoxo species.

Divergent mechanisms of iron-containing enzymes for hydrocarbon biosynthesis.

Increasing levels of energy consumption, dwindling resources, and environmental considerations have served as compelling motivations to explore renewable alternatives to petroleum-based fuels, including enzymatic routes for hydrocarbon synthesis. Phylogenetically diverse species have long been recognized to produce hydrocarbons, but many of the enzymes responsible have been identified within the past decade. The enzymatic conversion of Cn chain length fatty aldehydes (or acids) to Cn-1 hydrocarbons, alkanes or alkenes, involves a C-C scission reaction. Surprisingly, the enzymes involved in hydrocarbon synthesis utilize non-heme mononuclear iron, dinuclear iron, and thiolate-ligated heme cofactors that are most often associated with monooxygenation reactions. In this review, we examine the mechanisms of several enzymes involved in hydrocarbon biosynthesis, with specific emphasis on the structural and electronic changes that enable this functional switch.

Non-Porous Iron(II)-Based Sensor: Crystallographic Insights into a Cycle of Colorful Guest-Induced Topotactic Transformations.

Materials capable of sensing volatile guests at room temperature by an easily monitored set of outputs are of great appeal for development as chemical sensors of small volatile organics and toxic gases. Herein the dinuclear iron(II) complex, [FeII2 (L)2 (CH3 CN)4 ](BF4 )4 ⋅2 CH3 CN (1) [L=4-(4-methylphenyl)-3-(3-pyridazinyl)-5-pyridyl-4H-1,2,4-triazole], is shown to undergo reversible single-crystal-to-single-crystal (SCSC) transformations upon exposure to vapors of different guests: 1 (MeCN)⇌2 (EtOH)→3 (H2 O)⇌1 (MeCN). Whilst 1 and 2 remain dimetallic, SCSC to 3 involves conversion to a 1D polymeric chain (due to a change in L bridging mode), which, remarkably, can undergo SCSC de-polymerization, reforming dimetallic 1. Additionally, SC-XRD studies of two ordered transient forms, 1TF3 and 2TF3, confirm that guest exchange occurs by diffusion of the new guests into the non-porous lattices as the old guests leave. These reversible SCSC events also induce color and magnetic responses. Indeed dark red 1 is spin crossover active (T1/2 ↓ 356 K; T1/2 ↑ 369 K), whilst orange 2 and yellow 3 remain high spin.

Non‐Porous Iron(II)‐Based Sensor: Crystallographic Insights into a Cycle of Colorful Guest‐Induced Topotactic Transformations

AbstractMaterials capable of sensing volatile guests at room temperature by an easily monitored set of outputs are of great appeal for development as chemical sensors of small volatile organics and toxic gases. Herein the dinuclear iron(II) complex, [FeII2(L)2(CH3CN)4](BF4)4⋅2 CH3CN (1) [L=4‐(4‐methylphenyl)‐3‐(3‐pyridazinyl)‐5‐pyridyl‐4H‐1,2,4‐triazole], is shown to undergo reversible single‐crystal‐to‐single‐crystal (SCSC) transformations upon exposure to vapors of different guests: 1 (MeCN)⇌2 (EtOH)→3 (H2O)⇌1 (MeCN). Whilst 1 and 2 remain dimetallic, SCSC to 3 involves conversion to a 1D polymeric chain (due to a change in L bridging mode), which, remarkably, can undergo SCSC de‐polymerization, reforming dimetallic 1. Additionally, SC‐XRD studies of two ordered transient forms, 1TF3 and 2TF3, confirm that guest exchange occurs by diffusion of the new guests into the non‐porous lattices as the old guests leave. These reversible SCSC events also induce color and magnetic responses. Indeed dark red 1 is spin crossover active (T1/2↓ 356 K; T1/2↑ 369 K), whilst orange 2 and yellow 3 remain high spin.

A Carboxylate Shift Regulates Dioxygen Activation by the Diiron Nonheme β-Hydroxylase CmlA upon Binding of a Substrate-Loaded Nonribosomal Peptide Synthetase.

The first step in the nonribosomal peptide synthetase (NRPS)-based biosynthesis of chloramphenicol is the β-hydroxylation of the precursor l-p-aminophenylalanine (l-PAPA) catalyzed by the monooxygenase CmlA. The active site of CmlA contains a dinuclear iron cluster that is reduced to the diferrous state (WTR) to initiate O2 activation. However, rapid O2 activation occurs only when WTR is bound to CmlP, the NRPS to which l-PAPA is covalently attached. Here the X-ray crystal structure of WTR is reported, which is very similar to that of the as-isolated diferric enzyme in which the irons are coordinately saturated. X-ray absorption spectroscopy is used to investigate the WTR cluster ligand structure as well as the structures of WTR in complex with a functional CmlP variant (CmlPAT) with and without l-PAPA attached. It is found that formation of the active WTR:CmlPAT-l-PAPA complex converts at least one iron of the cluster from six- to five-coordinate by changing a bidentately bound amino acid carboxylate to monodentate on Fe1. The only bidentate carboxylate in the structure of WTR is E377. The crystal structure of the CmlA variant E377D shows only monodentate carboxylate coordination. Reduced E377D reacts rapidly with O2 in the presence or absence of CmlPAT-l-PAPA, showing loss of regulation. However, this variant fails to catalyze hydroxylation, suggesting that E377 has the dual role of coupling regulation of O2 reactivity with juxtaposition of the substrate and the reactive oxygen species. The carboxylate shift in response to substrate binding represents a novel regulatory strategy for oxygen activation in diiron oxygenases.

A mononuclear non-heme-iron dioxygen-carrying protein?

The ability of mononuclear non-heme iron complexes to function as molecular oxygen transporters is investigated by density functional theory. The factors governing the efficiency of the reversible binding of dioxygen at the active site of the dinuclear non-heme iron enzyme hemerythrin, including antiferromagnetic coupling and the conversion of dioxygen to hydroperoxo by a proton coupled 2-electron transfer mechanism, are revisited and considered as possible tools in mononuclear non-heme complexes. Several mononuclear non-heme model complexes, including active sites of enzymes already known to interact with dioxgenic ligands, are constructed and the molecular oxygen transportation capabilities of these complexes are examined computationally. The high-spin nature of the ground state of these complexes implies an intrinsic kinetic lability of the oxy structures, as also evident from potential energy surface calculations towards iron-dioxygen cleavage. Proton affinities as calibrated with reference compounds showed that these complexes are highly unlikely to undergo protonation to form hydroperoxo-like adducts. Mixed superoxo descriptions of the dissociated dioxygenic ligands in all complexes add to the overall conclusion that these model structures are significantly disadvantaged in any attempt to be employed for molecular oxygen transportation.

Coupling of Carbon Dioxide with Epoxides Efficiently Catalyzed by Thioether‐Triphenolate Bimetallic Iron(III) Complexes: Catalyst Structure–Reactivity Relationship and Mechanistic DFT Study

AbstractA series of dinuclear iron(III)I complexes supported by thioether‐triphenolate ligands have been prepared to attain highly Lewis acidic catalysts. In combination with tetrabutylammonium bromide (TBAB) they are highly active catalysts in the synthesis of cyclic organic carbonates through the coupling of carbon dioxide to epoxides with the highest initial turnover frequencies reported to date for the conversion of propylene oxide to propylene carbonate for iron‐based catalysts (5200 h−1; 120 °C, 2 MPa, 1 h). In particular, these complexes are shown to be highly selective catalysts for the coupling of carbon dioxide to internal oxiranes affording the corresponding cyclic carbonates in good yield and with retention of the initial stereochemical configuration. A density functional theory (DFT) investigation provides a rational for the relative high activity found for these Fe(III) complexes, showing the fundamental role of the hemilabile sulfur atom in the ligand skeleton to promote reactivity. Notably, in spite of the dinuclear nature of the catalyst precursor only one metal center is involved in the catalytic cycle.magnified image