Iron Model Complexes Research Articles

Probing Physical Oxidation State by Resonant X-ray Emission Spectroscopy: Applications to Iron Model Complexes and Nitrogenase.

The ability of resonant X‐ray emission spectroscopy (XES) to recover physical oxidation state information, which may often be ambiguous in conventional X‐ray spectroscopy, is demonstrated. By combining Kβ XES with resonant excitation in the XAS pre‐edge region, resonant Kβ XES (or 1s3p RXES) data are obtained, which probe the 3dn+1 final‐state configuration. Comparison of the non‐resonant and resonant XES for a series of high‐spin ferrous and ferric complexes shows that oxidation state assignments that were previously unclear are now easily made. The present study spans iron tetrachlorides, iron sulfur clusters, and the MoFe protein of nitrogenase. While 1s3p RXES studies have previously been reported, to our knowledge, 1s3p RXES has not been previously utilized to resolve questions of metal valency in highly covalent systems. As such, the approach presented herein provides chemists with means to more rigorously and quantitatively address challenging electronic‐structure questions.

Probing Physical Oxidation State by Resonant X‐ray Emission Spectroscopy: Applications to Iron Model Complexes and Nitrogenase

AbstractThe ability of resonant X‐ray emission spectroscopy (XES) to recover physical oxidation state information, which may often be ambiguous in conventional X‐ray spectroscopy, is demonstrated. By combining Kβ XES with resonant excitation in the XAS pre‐edge region, resonant Kβ XES (or 1s3p RXES) data are obtained, which probe the 3dn+1 final‐state configuration. Comparison of the non‐resonant and resonant XES for a series of high‐spin ferrous and ferric complexes shows that oxidation state assignments that were previously unclear are now easily made. The present study spans iron tetrachlorides, iron sulfur clusters, and the MoFe protein of nitrogenase. While 1s3p RXES studies have previously been reported, to our knowledge, 1s3p RXES has not been previously utilized to resolve questions of metal valency in highly covalent systems. As such, the approach presented herein provides chemists with means to more rigorously and quantitatively address challenging electronic‐structure questions.

Quantitative Interrelation between Atractylenolide I, II, and III in Atractylodes japonica Koidzumi Rhizomes, and Evaluation of Their Oxidative Transformation Using a Biomimetic Kinetic Model.

Analytical methods based on ultraperformance liquid chromatography/ion-trap mass spectrometry (UPLC/ion-trap MS) were developed for quantification of atractylenolide I, II, and III in the methanol extract of Atractylodes japonica rhizomes with a C18 column in an acidified water/acetonitrile gradient eluent in an LC system, and ion-trap MS coupled with electrospray ionization was employed under positive-ion mode. The three atractylenolides were quantified in all A. japonica samples, and the content of atractylenolide I, II, and III showed a significant correlation to each other. Such high correlation was explained by the mechanistic insights into the biosynthetic pathway of atractylenoide III and I from atractylenoide II by using the biomimetic cytochrome P450 model, [Fe(tmp)](CF3SO3) (tmp = meso-tetramesitylporphyrin). Atractylenolides could be transformed by oxidation via the oxidative enzyme in the A. japonica plant. The present study first reports the first oxidative transformation of atractylenolides using the heme iron model complex.

Observation of Radical Rebound in a Mononuclear Nonheme Iron Model Complex.

A nonheme iron(III) terminal methoxide complex, [FeIII(N3PyO2Ph)(OCH3)]ClO4, was synthesized. Reaction of this complex with the triphenylmethyl radical (Ph3C•) leads to formation of Ph3COCH3 and the one-electron-reduced iron(II) center, as seen by UV-vis, EPR, 1H NMR, and Mössbauer spectroscopy. These results indicate that homolytic Fe-O bond cleavage occurs together with C-O bond formation, providing a direct observation of the "radical rebound" process proposed for both biological and synthetic nonheme iron centers.

Thiol dioxygenase turnover yields benzothiazole products from 2-mercaptoaniline and O2-dependent oxidation of primary alcohols

Thiol dioxygenases are non-heme mononuclear iron enzymes that catalyze the O2-dependent oxidation of free thiols (-SH) to produce the corresponding sulfinic acid (-SO2-). Previous chemical rescue studies identified a putative FeIII-O2− intermediate that precedes substrate oxidation in Mus musculus cysteine dioxygenase (Mm CDO). Given that a similar reactive intermediate has been identified in the extradiol dioxygenase 2, 3-HCPD, it is conceivable that these enzymes share other mechanistic features with regard to substrate oxidation. To explore this possibility, enzymatic reactions with Mm CDO (as well as the bacterial 3-mercaptopropionic acid dioxygenase, Av MDO) were performed using a substrate analogue (2-mercaptoaniline, 2ma). This aromatic thiol closely approximates the catecholic substrate of homoprotocatechuate of 2, 3-HPCD while maintaining the 2-carbon thiol-amine separation preferred by Mm CDO. Remarkably, both enzymes exhibit 2ma-gated O2-consumption; however, none of the expected products for thiol dioxygenase or intra/extradiol dioxygenase reactions were observed. Instead, benzothiazoles are produced by the condensation of 2ma with aldehydes formed by an off-pathway oxidation of primary alcohols added to aqueous reactions to solubilize the substrate. The observed oxidation of 1º-alcohols in 2ma-reactions is consistent with the formation of a high-valent intermediate similar to what has been reported for cytochrome P450 and mononuclear iron model complexes.

Iron L2,3-Edge X-ray Absorption and X-ray Magnetic Circular Dichroism Studies of Molecular Iron Complexes with Relevance to the FeMoco and FeVco Active Sites of Nitrogenase.

Herein, a systematic study of a series of molecular iron model complexes has been carried out using Fe L2,3-edge X-ray absorption (XAS) and X-ray magnetic circular dichroism (XMCD) spectroscopies. This series spans iron complexes of increasing complexity, starting from ferric and ferrous tetrachlorides ([FeCl4]−/2–), to ferric and ferrous tetrathiolates ([Fe(SR)4]−/2–), to diferric and mixed-valent iron–sulfur complexes [Fe2S2R4]2–/3–. This test set of compounds is used to evaluate the sensitivity of both Fe L2,3-edge XAS and XMCD spectroscopy to oxidation state and ligation changes. It is demonstrated that the energy shift and intensity of the L2,3-edge XAS spectra depends on both the oxidation state and covalency of the system; however, the quantitative information that can be extracted from these data is limited. On the other hand, analysis of the Fe XMCD shows distinct changes in the intensity at both L3 and L2 edges, depending on the oxidation state of the system. It is also demonstrated that the XMCD intensity is modulated by the covalency of the system. For mononuclear systems, the experimental data are correlated with atomic multiplet calculations in order to provide insights into the experimental observations. Finally, XMCD is applied to the tetranuclear heterometal–iron–sulfur clusters [MFe3S4]3+/2+ (M = Mo, V), which serve as structural analogues of the FeMoco and FeVco active sites of nitrogenase. It is demonstrated that the XMCD data can be utilized to obtain information on the oxidation state distribution in complex clusters that is not readily accessible for the Fe L2,3-edge XAS data alone. The advantages of XMCD relative to standard K-edge and L2,3-edge XAS are highlighted. This study provides an important foundation for future XMCD studies on complex (bio)inorganic systems.

生体模倣型オスミウム錯体を触媒とするアルケンの酸化的変換反応

Metallo-enzymes catalyze a variety of chemical transformation reactions such as oxidation, reduction, coupling, and hydrolysis, most of which are essential for synthetic organic chemistry. Rieske dioxygenases, one of the most abundant nonheme iron enzyme family, catalyzes selective cis-dihydroxylation of arene C=C double bonds using molecular oxygen or hydrogen peroxide. The iron model complexes have so far been developed and employed in cis-dihydroxylation of alkenes as a catalyst. However, there are several drawbacks in the iron model systems such as stability, substrate limitation, low substrate and oxidant conversion, and low product selectivity. To make more efficient catalytic systems, the authors have developed osmium-complexes as the model compounds of the Rieske dioxygenase reaction center. Herein, the authors employ them as the catalyst for cis-dihydroxylation of alkenes. The active oxidant has been identified, and the catalytic mechanism has been explored based on the kinetic analysis and DFT calculations. Furthermore, the catalytic system has been applied to oxidative cyclization of 1,5-dienes to afford tetrahydrofuran derivatives and to aminohydroxylation of alkenes to give cis-1,2-aminoalcohols.

A Functional Model of [Fe]-Hydrogenase.

[Fe]-Hydrogenase catalyzes the hydrogenation of a biological substrate via the heterolytic splitting of molecular hydrogen. While many synthetic models of [Fe]-hydrogenase have been prepared, none yet are capable of activating H2 on their own. Here, we report the first Fe-based functional mimic of the active site of [Fe]-hydrogenase, which was developed based on a mechanistic understanding. The activity of this iron model complex is enabled by its unique ligand environment, consisting of biomimetic pyridinylacyl and carbonyl ligands, as well as a bioinspired diphosphine ligand with a pendant amine moiety. The model complex activates H2 and mediates hydrogenation of an aldehyde.

Catalytic conversion of nitrogen to ammonia by an iron model complex

The reduction of N2 to NH3 is a requisite transformation for life.1 While it is widely appreciated that the iron-rich cofactors of nitrogenase enzymes facilitate this transformation,2-5 how they do so remains poorly understood. A central element of debate has been the exact site(s) of nitrogen coordination and reduction.6,7 The synthetic inorganic community placed an early emphasis on Mo8, because Mo was thought to be an essential element of nitrogenases3 and because pioneering work by Chatt and coworkers established that well-defined Mo model complexes could mediate the stoichiometric conversion of N2 to NH3.9 This chemical transformation can be performed in a catalytic fashion by two well-defined molecular systems that feature Mo centres.10,11 However, it is now thought that Fe is the only transition metal essential to all nitrogenases,3 and recent biochemical and spectroscopic data has implicated Fe instead of Mo as the site of N2 binding in the FeMo-cofactor.12 In this work, we describe a tris(phosphine)borane-supported Fe complex that catalyzes the reduction of N2 to NH3 under mild conditions, wherein >40% of the H+/e- equivalents are delivered to N2. Our results indicate that a single Fe site may be capable of stabilizing the various NxHy intermediates generated en route to catalytic NH3 formation. Geometric tunability at Fe imparted by a flexible Fe-B interaction in our model system appears to be important for efficient catalysis.13-15 We propose that the interstitial light C-atom recently assigned in the nitrogenase cofactor may play a similar role,16,17 perhaps by enabling a single Fe site to mediate the enzymatic catalysis via a flexible Fe-C interaction.18

Sensitivity of X-ray Core Spectroscopy to Changes in Metal Ligation: A Systematic Study of Low-Coordinate, High-Spin Ferrous Complexes

In order to assess the sensitivity and complementarity of X-ray absorption and emission spectroscopies for determining changes in the metal ligation sphere, a systematic experimental and theoretical study of iron model complexes has been carried out. A series of high-spin ferrous complexes, in which the ligation sphere has been varied from a three-coordinate complex, [L(tBu)Fe(SPh)] (1) (where L(tBu) = bulky β-diketiminate ligand; SPh = phenyl thiolate) to four-coordinate complexes [L(tBu)Fe(SPh)(X)] (where X = CN(t)Bu (2); 1-methylimidazole (3); or N,N-dimethylformamide (DMF) (4)), has been investigated using a combination of Fe K-edge X-ray absorption (XAS) and Kβ X-ray emission (XES) spectroscopies. The Fe K XAS pre-edge and edge of all four complexes are consistent with a high-spin ferrous assignment, with the largest differences in the pre-edge intensities attributed to changes in covalency of the fourth coordination site. The X-ray emission spectra show pronounced changes in the valence to core region (V2C) as the identity of the coordinated ligand is varied. The experimental results have been correlated to density functional theory (DFT) calculations, to understand key molecular orbital contributions to the observed absorption and emission features. The calculations also have been extended to a series of hypothetical high-spin iron complexes to understand the sensitivity of XAS and XES techniques to different ligand protonation states ([L(tBu)Fe(II)(SPh)(NHn)](3-n) (n = 3, 2, 1, 0)), metal oxidation states [L(tBu)Fe(SPh)(N)](n-) (n = 3, 2, 1), and changes in the ligand identity [L(tBu)Fe(IV)(SPh)(X)](n-) (X = C(4-), N(3-), O(2-); n = 2, 1, 0). This study demonstrates that XAS pre-edge data have greater sensitivity to changes in oxidation state, while valence to core (V2C) XES data provide a more sensitive probe of ligand identity and protonation state. The combination of multiple X-ray spectroscopic methods with DFT results thus has the potential to provide for detailed characterization of complex inorganic systems in both chemical and biological catalysis.

Oxygen atom transfer mediated by an iron(IV)/iron(II) macrocyclic complex containing pyridine and tertiary amine donors

A new non-heme iron model complex containing a high-spin iron(II) complexed with N-methylated pyridine-containing macrocycle was synthesized and crystallographically characterized. The complex generates peroxo- and high-valent iron-oxo intermediates in reactions with tert-butylhydroperoxide and isopropyl 2-iodoxybenzoate, respectively, allowing to gain insight into the formation and reactivity of enzyme-like intermediates related to biological oxygen activation. The formation and reactivity of these intermediate species were investigated by the stopped-flow methodology. The mechanism of oxygen transfer to organic substrates involving reaction of oxoiron(IV) intermediate was elucidated on the basis of spectroscopic and kinetic data. Incorporation of a pyridine ring into the macrocycle increased the reactivity of the FeIVO intermediates in comparison with polyamine tetraaza macrocyclic complexes: ferryl (FeIVO) species derived from 3 demonstrated electrophilic reactivity in transferring an oxygen atom to substituted triarylphosphines and to olefins (such as cyclooctene). However, iron(III) alkylperoxo intermediate was unreactive with cyclooctene.

Mechanistic investigation of cyclohexane oxidation by a non-heme iron complex: evidence of product inhibition by UV/vis stopped-flow studies

We report herein studies examining a binuclear non-heme iron model complex that is capable of catalytically oxidizing cyclohexane to cyclohexanol in excess of 200 turnovers, relative to the iron complex, and cyclohexanone (5 turnovers) via heterolytic cleavage of the mechanistic probe peroxide MPPH. Low-temperature stopped-flow electronic spectroscopy was utilized to investigate the mechanism of the reaction of this diiron(II) compound, Fe(2)(H(2)Hbamb)(2)(N-MeIm)(2), (H(2)Hbamb = 2,3-bis(2-hydroxybenzamido)dimethylbutane) (1) with MPPH. In the absence of substrates, the reaction proceeds in three consecutive steps starting with oxygen atom transfer to the diferrous complex to generate a putative [Fe(IV)=O species], thought to be the oxidant in the catalytic cycle. Over time, the rate of catalysis is observed to decrease without consumption of all available peroxide. By utilizing low-temperature stopped-flow UV/vis kinetic studies, the diferrous complex, 1, is shown to undergo product inhibition arising from the interaction of either cyclohexanol or MPP-OL product species to the diiron center, therefore precluding further reaction with MPPH.

Prediction of Iron K-Edge Absorption Spectra Using Time-Dependent Density Functional Theory

Iron K-edge X-ray absorption pre-edge features have been calculated using a time-dependent density functional approach. The influence of functional, solvation, and relativistic effects on the calculated energies and intensities has been examined by correlation of the calculated parameters to experimental data on a series of 10 iron model complexes, which span a range of high-spin and low-spin ferrous and ferric complexes in O(h) to T(d) geometries. Both quadrupole and dipole contributions to the spectra have been calculated. We find that good agreement between theory and experiment is obtained by using the BP86 functional with the CP(PPP) basis set on the Fe and TZVP one of the remaining atoms. Inclusion of solvation yields a small improvement in the calculated energies. However, the inclusion of scalar relativistic effects did not yield any improved correlation with experiment. The use of these methods to uniquely assign individual spectral transitions and to examine experimental contributions to backbonding is discussed.

Trigonal-Bipyramidal Geometry Induced by an External Water Ligand in a Sterically Hindered Iron Salen Complex, Related to the Active Site of Protocatechuate 3,4-Dioxygenase

A unique distorted trigonal-bipyramidal geometry observed for the non-heme iron center in protocatechuate 3,4-dioxygenase (3,4-PCD) was carefully examined utilizing a sterically hindered iron salen complex, which well reproduces the endogenous His2Tyr2 donor set with water as an external ligand. X-ray crystal structures of a series of iron model complexes containing bis(3,5-dimesitylsalicylidene)-1,2-dimesitylethylenediamine indicate that a distorted trigonal-bipyramidal geometry is achieved upon binding of water as an external ligand. The extent of a structural change of the iron center from a preferred square-pyramidal to a distorted trigonal-bipyramidal geometry varies with the external ligand that is bound in the order Cl << EtO < H2O, which is consistent with the spectrochemical series. The distortion in the model system is not due to steric repulsions but electronic interactions between the external ligand and the iron center, as evidenced from the X-ray crystal structures of another series of iron model complexes with a less-hindered bis(3-xylylsalicylidene)-1,2-dimesitylethylenediamine ligand, as well as by density functional theory calculations. Further spectroscopic investigations indicate that a unique distorted trigonal-bipyramidal geometry is indeed maintained even in solution. The present model study provides a new viewpoint that a unique distorted trigonal-bipyramidal iron site might not be preorganized by a 3,4-PCD protein but could be electronically induced upon the binding of an external hydroxide ligand to the iron(III) center. The structural change induced by the external water ligand is also discussed in relation to the reaction mechanism of 3,4-PCD.

Performance of Nonrelativistic and Quasi-Relativistic Hybrid DFT for the Prediction of Electric and Magnetic Hyperfine Parameters in57Fe Mössbauer Spectra

57Fe electric and magnetic hyperfine parameters were calculated for a series of 10 iron model complexes, covering a wide range of oxidation and spin states. Employing the B3LYP hybrid method, results from nonrelativistic density functional theory (DFT) and quasi-relativistic DFT within the zero-order regular approximation (ZORA) were compared. Electron densities at the iron nuclei were calculated and correlated with experimental isomer shifts. It was shown that the fit parameters do not depend on a specific training set of iron complexes and are, therefore, more universal than might be expected. The nonrelativistic and quasi-relativistic electron densities gave fit parameters of similar quality; the ZORA densities are only shifted by a factor of 1.32, upward in the direction of the four-component Dirac-Fock value. From a correlation of calculated electric field gradients and experimental quadrupole splittings, the value of the 57Fe nuclear quadrupole moment was redetermined to a value of 0.16 barn, in good agreement with other studies. The ZORA approach gave no additional improvement of the calculated quadrupole splittings in comparison to the nonrelativistic approach. The comparison of the calculated and measured 57Fe isotropic hyperfine coupling constants (hfcc's) revealed that both the ZORA approach and the inclusion of spin-orbit contributions lead to better agreement between theory and experiment in comparison to the nonrelativistic results. For all iron complexes with small spin-orbit contributions (high-spin ferric and ferryl systems), a distinct underestimation of the isotropic hfcc's was found. Scaling factors of 1.81 (nonrelativistic DFT) and 1.69 (ZORA) are suggested. The calculated 57Fe isotropic hfcc's of the remaining model systems (low-spin ferric and high-spin ferrous systems) contain 10-50% second-order contributions and were found to be in reasonable agreement with the experimental results. This is assumed to be the consequence of error cancellation because g-tensor calculations for these systems are of poor quality with the existing DFT approaches. Excellent agreement between theory and experiment was found for the 57Fe anisotropic hfcc's. Finally, all of the obtained fit parameters were used for an application study of the [Fe(H2O)6]3+ ion. The calculated spectroscopic data are in good agreement with the Mossbauer and electron paramagnetic resonance results discussed in detail in a forthcoming paper.

Reactivity of methane mono-oxygenase, insights from quantum mechanic studies on synthetic iron model complexes

Methane mono-oxygenase (MMO) and deoxyhemerythrin (DHr) are examples of di-iron enzymes that catalyze the dissociative and non-dissociative binding of molecular oxygen. To mimic the MMO active site with a finite cluster, we chose to study the binuclear heptapodate coordinated iron(III)-complexes of N,N,N′,N′-tetrakis(2-benzimidazolylmethyl)-2-hydroxy-1,3-diamino-propane (HPTB) and N,N,N′,N′-tetrakis(2-pyridylmethyl)-2-hydroxy-1,3-diamino-propane (HPTP). These have active sites of the form [Fe 2(HPTP)(μ-OH)] 4+ (1) and [Fe 2(HPTB)(μ-OH)] 4+ (2). Quantum mechanics structures are compared with the experimental data obtained from the EXAFS analysis. For the O 2 binding on the reduced active site, the μ-η 1:η 1-O 2 mode seems the slightly more stable precursor to the OFeOFeO bis-ferryl (re)active site. The nature of the ferryl groups are these of a reactive two center three electron bond.

EXAFS STUDY OF ACTIVE INTERMEDIATES : HEME ENZYMES AND MODEL COMPOUNDS

The iron coordination structures of the oxygenated cytochrome P-450-CAM and chloroperoxidase and of a number of penta- and hexa-coordinate ferrous porphyrin complexes containing biologically relevant, sulfur axial ligands have been investigatied by EXAFS spectroscopy. The two oxygenated enzymes have both been found to contain a sulfur atom located 2.37 A from the central heme iron. In the CO-ligated series of model complexes, two distinct categories of Fe-Sax distances have been observed that correlate with thiolate and non-thiolate ligation (~2.33 and ~2.41 A, respectively) . The data for these model ferrous-CO ccomplexes, together with previously reported Fe-S distance in oxygenated heme iron model complexes ; allows the sulfur atoms in oxygenated P-450-CAM and chloroperoxidase to be identified as a thiolate sulfur.