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Bridging oxo species are important in the synthetic and biological chemistry of iron, and are found with iron oxidation states from +2 to +4. We report the first oxodiiron(II) complex that has been crystallographically characterized. It has been examined by NMR, IR, and Mössbauer spectroscopies as well as density-functional calculations.
The reaction of [Fe(II)(beta-BPMCN)(OTf)2] (1, BPMCN = N,N'-bis(2-pyridylmethyl)-N,N'-dimethyl-trans-1,2-diaminocyclohexane) with tBuOOH at low-temperature yields alkylperoxoiron(III) intermediates 2 in CH2Cl2 and 2-NCMe in CH3CN. At -45 degrees C and above, 2-NCMe converts to a pale green species 3 (lambda(max) = 753 nm, epsilon = 280 M(-1) cm(-1)) in 90% yield, identified as [Fe(IV)(O)(BPMCN)(NCCH3)]2+ by comparison to other nonheme [Fe(IV)(O)(L)]2+ complexes. Below -55 degrees C in CH2Cl2, 2 decays instead to form deep turquoise 4 (lambda(max) = 656, 845 nm; epsilon = 4000, 3600 M(-1) cm(-1)), formulated to be an unprecedented alkylperoxoiron(IV) complex [Fe(IV)(BPMCN)(OH)(OOtBu)]2+ on the basis of Mössbauer, EXAFS, resonance Raman, NMR, and mass spectral evidence. The reactivity of 1 with tBuOOH in the two solvents reveals an unexpectedly rich iron(IV) chemistry that can be supported by the BPMCN ligand.
Carboxylate-rich diiron(II) compounds with varying numbers of water ligands have been characterized, including the first complex with a {Fe2(mu-OH2)2(mu-O2CArTol)}3+ unit. The isolation of these complexes reveals how water can alter the structural properties of carboxylate-bridged diiron(II) core similar to those that occur in a variety of dioxygen-activating metalloenzyme cores. Mössbauer and variable temperature, variable field magnetic susceptibility experiments indicate that the compound [Fe2(mu-OH2)2(mu-O2CAr4F-Ph)(O2CAr4F-Ph)3(THF)2(OH2)] has a high-spin diiron(II) core with little significant magnetic exchange coupling.
(mu-Hydroxo or oxo)(mu-1,2-peroxo)diiron(III) complexes having a tetradentate tripodal ligand (L) containing a carboxylate sidearm [Fe2(mu-OH or mu-O)(mu-O2)(L)2]n+ were synthesized as models for peroxo-intermediates of non-heme diiron proteins and characterized by various physicochemical measurements including X-ray analysis, which provide fundamental structural and spectroscopic insights into the peroxodiiron(III) complexes.
Quinolinic acid is an intermediate in the biosynthesis of nicotinamide-containing redox cofactors. The ultimate step in the formation of quinolinic acid in prokaryotes is the condensation of iminosuccinate and dihydroxyacetone phosphate, which is catalyzed by the product of the nadA gene in Escherichia coli. A combination of UV-vis, Mössbauer, and EPR spectroscopies, along with analytical methods for the determination of iron and sulfide, demonstrates for the first time that anaerobically purified quinolinate synthetase (NadA) from E. coli contains one [4Fe-4S] cluster per polypeptide. The protein is active, catalyzing the formation of quinolinic acid with a Vmax [ET]-1 of 0.01 s-1.
The iron-sulfur cluster-free hydrogenase (Hmd) from methanogenic archaea harbors an iron-containing, light-sensitive cofactor of still unknown structure as prosthetic group. The enzyme is reversibly inhibited by CO and cyanide and is EPR silent. We report here on Mössbauer spectra of the (57)Fe-labeled enzyme and of the isolated cofactor. The spectrum of the holoenzyme measured at 80 K revealed a doublet peak with an isomer shift delta = 0.06 mm.s(-)(1) and a quadrupole splitting of DeltaE(Q) = 0.65 mm.s(-)(1) (at pH 8.0). The signal intensity corresponded to the enzyme concentration assuming 1 Fe per mol active site. Upon addition of CO or cyanide to the enzyme, the isomer shift decreased to -0.03 mm.s(-)(1) and -0.00(1) mm.s(-)(1), and the quadrupole splitting increased to 1.38 mm.s(-)(1) and 1.75 mm.s(-)(1), respectively. The three spectra could be perfectly simulated assuming the presence of only one type of iron in Hmd. The low isomer shift is characteristic for Fe in a low oxidation state (0, +1, +2). When the spectra of the holoenzyme and of the CO- or cyanide-inhibited enzyme were measured at 4 K in a magnetic field of 4 and 7 T, the spectra obtained could be simulated assuming the presence of only the external magnetic field, which excludes that the iron in the active site of Hmd is Fe(I), high-spin Fe(0), or high-spin Fe(II). Mössbauer spectra of the isolated Hmd cofactor are also reported.
Current theoretical and experimental evidence points toward X = N as the identity of the interstitial atom in the [MoFe7S9X] core of the iron-molybdenum cofactor cluster of nitrogenase. This atom functions with mu6 bridging multiplicity to six iron atoms and, if it is nitrogen as nitride, raises a question as to the existence of a family of molecular iron nitrides of higher nuclearity than known dinuclear Fe(III,IV) species with linear [Fe-N-Fe]5+,4+ bridges. This matter has been initially examined by variation of reactant stoichiometry in the self-assembly systems [FeX4]1-/(Me3Sn)3N (X = Cl-, Br-) in acetonitrile. A 2:1 mol ratio affords [Fe4N2Cl10]4- (1), isolated as the Et4N+ salt (72%). This cluster has idealized C2h symmetry with a planar antiferromagnetically coupled [Fe(III)4(mu3-N)2]6+ core containing an Fe2N2 rhombus to which are attached two FeCl3 units. DFT calculations have been performed to determine the dominant magnetic exchange pathway. An 11:8 mol ratio leads to [Fe10N8Cl12]5- (3) as the Et4N+ salt (37%). The cluster possesses idealized D2h symmetry and is built of 15 edge- and vertex-shared rhomboids involving two mu3-N and six mu4-N bridging atoms, and incorporates two of the core units of 1. Four FeN2Cl2 and four FeN3Cl sites are tetrahedral and two FeN5 sites are trigonal pyramidal. The cluster is mixed-valence (9Fe(III) + Fe(IV)); a discrete Fe(IV) site was not detected by crystallography or Mössbauer spectroscopy. The corresponding clusters [Fe4N2Br10]4- and [Fe10N8Br12]5- are isostructural with 1 and 3, respectively. Future research is directed toward defining the scope of the family of molecular iron nitrides.
The active species, Compound I, of horseradish peroxidase (HRP) has been investigated by quantum mechanical/molecular mechanical (QM/MM) calculations using 10 different QM regions. In accord with experimental data, the lowest doublet and quartet states are found to be virtually degenerate, with two unpaired electrons on the FeO moiety and one localized on the porphyrin in an a(2u)-dominant orbital with a minor, but nonnegligible, a(1u) component. The proximal ligand appears to be imidazole rather than imidazolate. The hydrogen-bonding network around the FeO moiety (i.e., Arg38 and His42) has significant influence on the axial bonds and the spin density distribution in the FeO moiety. Including this network in the QM region was found to be essential for reproducing the experimental Mössbauer parameters. The protein environment shapes most of the subtle features of Compound I of HRP.
The tetraheme cytochrome c(554) (cyt c(554)) from Nitrosomonas europaea is believed to function as an electron-transfer protein from hydroxylamine oxidoreductase (HAO). We show here that cyt c(554) also has significant NO reductase activity. The protein contains one high-spin and three low-spin c-type hemes. HAO catalyzed reduction of the cyt c(554), ligand binding, intermolecular electron transfer, and kinetics of NO reduction by cyt c(554) have been investigated. We detect the formation of a NO-bound ferrous heme species in cyt c(554) by EPR and Mössbauer spectroscopies during the HAO catalyzed oxidation of hydroxylamine, indicating that N-oxide intermediates produced from HAO readily bind to cyt c(554). In the half-reduced state of cyt c(554), we detect a spin interaction between the [FeNO](7) state of heme 2 and the low-spin ferric state of heme 4. We find that ferrous cyt c(554) will reduce NO at a rate greater than 16 s(-1), which is comparable to rates of other known NO reductases. Carbon monoxide or nitrite are shown not to bind to the reduced protein, and previous results indicate the reactions with O(2) are slow and that a variety of ligands will not bind in the oxidized state. Thus, the enzymatic site is highly selective for NO. The NO reductase activity of cyt c(554) may be important during ammonia oxidation in N. europaea at low oxygen concentrations to detoxify NO produced by reduction of nitrite or incomplete oxidation of hydroxylamine.
Crystalline samples of four low-spin Fe(III) octaalkyltetraphenylporphyrinate and two low-spin Fe(III) tetramesitylporphyrinate complexes, all of which are models of the bis-histidine-coordinated cytochromes of mitochondrial complexes II, III, and IV and chloroplast complex b(6)f, and whose molecular structures and EPR spectra have been reported previously, have been investigated in detail by Mössbauer spectroscopy. The six complexes and the dihedral angles between axial ligand planes of each are [(TMP)Fe(1-MeIm)(2)]ClO(4) (0 degree), paral-[(OMTPP)Fe(1-MeIm)(2)]Cl (19.5 degrees), paral-[(TMP)Fe(5-MeHIm)(2)]ClO(4) (26 degrees, 30 degrees for two molecules in the unit cell whose EPR spectra overlap), [(OETPP)Fe(4-Me(2)NPy)(2)]Cl (70 degrees), perp-[(OETPP)Fe(1-MeIm)(2)]Cl (73 degrees), and perp-[(OMTPP)Fe(1-MeIm)(2)]Cl (90 degrees). Of these, the first three have been shown to exhibit normal rhombic EPR spectra, each with three clearly resolved g-values, while the last three have been shown to exhibit "large g(max)" EPR spectra at 4.2 K. It is found that the hyperfine coupling constants of the complexes are consistent with those reported previously for low-spin ferriheme systems, with the largest-magnitude hyperfine coupling constant, A(zz), being considerably smaller for the "parallel" complexes (400-540 kG) than for the strictly perpendicular complex (902 kG), A(xx) being negative for all six complexes, and A(zz) and A(xx) being of similar magnitude for the "parallel" complexes (for example, for [(TMP)Fe(1-MeIm)(2)]Cl, A(zz) = 400 kG, A(xx) = -400 kG). In all cases, A(yy) is small but difficult to estimate with accuracy. With results for six structurally characterized model systems, we find for the first time qualitative correlations of g(zz), A(zz), and DeltaE(Q) with axial ligand plane dihedral angle Deltavarphi.
Using a combination of density functional calculations and Mössbauer spectroscopy, we have examined chloroperoxidase compound II (CPO-II). The Mössbauer spectrum of CPO-II suggests the presence of two distinct ferryl species in an approximately 70:30 ratio. Density functional calculations and cryogenic reduction and annealing experiments allow us to assign the major species as an Fe(IV)OH intermediate. The Mössbauer parameters of the minor component are indicative of an authentic iron(IV)oxo species, but we have found the 70:30 ratio to be pH invariant. The unchanging ratio of component concentrations is in agreement with CPO-II's visible absorption spectrum, which shows no change over the enzyme's range of pH stability.
QM and QM/MM calculations on Compound II, the enigmatic species in the catalytic cycle of the horseradish peroxidase enzyme, reveal six low-lying isomers. The principal isomer is the triplet oxo-ferryl form (PorFe(IV)=O) that yields the hydroxo-ferryl isomer (PorFe(IV)-OH+). These are the only forms observed in experimental studies. Theory shows, however, that these are the least stable isomers of Compound II. The two most stable forms are the singlet and triplet states of the Por+*Fe(III)-OH electromer. In addition, theory reveals species never considered in heme enzymes: the singlet and triplet states of the Por+*Fe(III)-OH2 electromer. The computational results reproduce the experimental features of the known isomers and enable us to draw relationships and make predictions regarding the missing ones. For example, while the "surprise" species, singlet and triplet Por+*Fe(III)-OH2, have never been considered in heme chemistry, the calculated Fe-O bond lengths indicate that these isomers may have, in fact, been observed in one of the two opposing EXAFS studies reported previously. Furthermore, these ferric-aqua complexes could be responsible for the reported 18O exchange with bulk water. It is clear, therefore, that the role of Compound II in the HRP cycle is considerably more multi-faceted than has been revealed so far. Our suggested multi-state reactivity scheme provides a paradigm for Compound II species. The calculated Mössbauer parameters may be helpful toward eventual characterization of these missing isomers of Compound II.
This work reports Mössbauer and DFT studies of the diiron-N2 complex LMeFeNNFeLMe (L = beta-diketiminate), 1a. Complex 1a, formally diiron(I), has a system spin S = 3 with an isolated MS = +/-3 quasi-doublet as a ground state; the MS = +/-2 doublet is >100 cm-1 higher in energy. Complex 1a exhibits at 4.2 K a large, positive magnetic hyperfine field, Bint = +68.1 T, and an effective g value of 16 +/- 2 along the easy magnetization axis of the ground doublet; this value is significantly larger than the spin-only value (g = 12). These results have been rationalized by DFT calculations, which show that each Fe site donates significant electron density into the pi* orbitals of dinitrogen, resulting in a configuration best described as two high-spin FeII (Sa = Sb = 2) bridged by triplet N22- (Sc = 1). In this description the minority spin electron of each iron is accommodated by two nonbonding, closely spaced 3d orbitals, z2 and yz (z is perpendicular to the diketiminate planes, x is along the Fe...Fe vector). Spin-orbit coupling between these orbital states generates a large unquenched orbital momentum along the iron-iron vector. The S = 3 ground state of 1a results from strong antiferromagnetic direct exchange couplings of the Fe spins (Sa = Sb = 2) to the N22- spin (Sc = 1) and can be formulated as ((Sa,Sb)Sab = 4, Sc = 1), S = 3>; H = J(Sa + Sb).Sc with J approximately 3500 cm-1.
Using a combination of Mössbauer spectroscopy and density functional calculations, we have determined that the ferryl forms of P450(BM3) and P450cam are protonated at physiological pH. Density functional calculations were performed on large active-site models of these enzymes to determine the theoretical Mössbauer parameters for the ferryl and protonated ferryl (Fe(IV)OH) species. These calculations revealed a significant enlargement of the quadrupole splitting parameter upon protonation of the ferryl unit. The calculated quadrupole splittings for the protonated and unprotonated ferryl forms of P450(BM3) are DeltaE(Q) = 2.17 mm/s and DeltaE(Q) = 1.05 mm/s, respectively. For P450cam, they are DeltaE(Q) = 1.84 mm/s and DeltaE(Q) = 0.66 mm/s, respectively. The experimentally determined quadrupole splittings (P450(BM3), DeltaE(Q) = 2.16 mm/s; P450cam, DeltaE(Q) = 2.06 mm/s) are in good agreement with the values calculated for the protonated forms of the enzymes. Our results suggest that basic ferryls are a natural consequence of thiolate-ligated hemes.
The interaction of Fe(3+) with the anthracycline anticancer drug idarubicin (Ida) was studied by absorption, CD, Mössbauer, and EPR spectroscopy. The formation of two major Fe(3+)-Ida complexes, labeled I and II, was observed. In complex I, Fe(3+) ion was bound to anthracycline at the {C(12)=O; C(11)-O(-)} coordination site. In complex II, two Fe(3+) ions were bound at sites {C(5)=O; C(6)-O(-)} and {C(12)=O; C(11)-O(-)}, respectively. Complex I was an equimolar monomeric species with a 1:1 Fe(3+):Ida stoichiometry (beta(1) = 4.8 x 10(11) M(-1)), whereas in complex II the anthracycline ligand was bridging two metal ions, alternatively bound to both anthracycline ring chelating sites with the assumption that the ratio of Fe(3+):Ida in complex II was 2:1 (beta(2) = 5.3 x 10(24) M(-2)). Alternatively, complex II may be oligomeric with Fe(3+):Ida = 1:1 and with each Fe(3+) bridging two Ida molecules. Our findings could be important in understanding the biological effects of the anthracycline-ferric complexes. Thus, providing information about the nature of the Fe(3+)-Ida system, we suggest that the formal 1:3 Fe(3+):anthracycline complexes, reported in the previous literature, could be a mixture of species I, II, and free ligand.
The pentacoordinated ferric and ferrous cytochrome P450(cam) complexes have been investigated by combined quantum mechanical/molecular mechanical (QM/MM) calculations in the presence of a protein/solvent environment and by QM calculations on the isolated QM regions with use of density functional theory. The B3LYP functional has been found more reliable than the BLYP and BHLYP functionals for estimating the relative state energies. The B3LYP/CHARMM calculations with an all-electron basis set for iron give high-spin ground states for the title complexes, in agreement with experiment. The comparison of the B3LYP/CHARMM results of the entire protein system with the B3LYP calculations on the naked QM regions shows that the amount of stabilization by the protein environment is largest for the intermediate-spin states, followed by the high-spin states of the complexes. The calculation of Mössbauer parameters in the presence of the enzyme environment confirms the double occupation of the d(xz) orbital in the quintet spin state of the ferrous complex, consistent with the computed QM/MM energies in the enzyme environment, while the d(x)2(-)(y)2 orbital is doubly occupied in the gas-phase quintet state.
Carbonaceous surface species and bulk iron carbides formed under realistic Fischer-Tropsch synthesis (FTS) conditions on moderately dispersed, active silica-supported iron catalysts (Fe/SiO2, FePt/SiO2, and FePtK/SiO2) were characterized. Bulk iron phase compositions were determined by Mössbauer spectroscopy and phase transformations of carbonaceous species during pretreatment with CO, H2, or H2/CO and following reaction were characterized using temperature-programmed hydrogenation (TPH). Isothermal transient rates of FTS were also measured for catalysts after different pretreatments. Six surface and bulk carbonaceous species were quantitatively identified from combined TPH and Mössbauer spectra of the FePtK catalyst. They include, in order of decreasing reactivity, (a) adsorbed, atomic carbon; (b) amorphous, lightly polymerized hydrocarbon or carbon surface species; (c) bulk epsilon' and chi carbides (Fe(2.2)C and Fe(2.5)C); and (d) disordered and moderately ordered graphitic surface carbons. A correlation between the amount of reactive alpha-carbon (C(alpha)) and initial catalytic activity was established. The method of Li et al. for measuring irreversible chemisorption of CO does not appear to provide quantitative measurements of active site densities on silica-supported iron. Models, based on this and previous work, are proposed for iron phase and carbon phase transformations in silica-supported iron during pretreatment, FTS, and postreaction passivation/oxidation.
Iron speciation by Mössbauer spectroscopy indicates that ferric iron in an aluminosilicate glass phase is the source of the bioavailable iron in coal fly ash and that this iron species is associated with combustion particles, but not with crustal dust derived from soil minerals. Urban particulate has been shown to be a source of bioavailable iron and has been shown to be able to induce the formation of reactive species in cell culture experiments. Crustal dust and laboratory-generated coal fly ash have been studied as surrogates for two sources of metal-bearing particles in ambient air. As much as a 60-fold difference in the amount of iron mobilized by the chelator citrate was observed between fly ash and crustal dust samples with similar total iron contents. The extent of iron mobilization by citrate in vitro has been shown to correlate with indirect measures of excess iron in cultured cells and with assays for reactive oxygen species generation in vitro. Mössbauer spectroscopy of coal fly ash, before and after treatment with the chelator desferrioxamine B, showed that the iron in an aluminosilicate glass phase was preferentially removed. The removal of the glass-phase iron greatly reduced the amount of iron that could be mobilized by citrate and prevented the particles from inducing interleukin-8 in cultured human lung epithelial (A549) cells. Ferric iron in aluminosilicate glass is associated with particles formed at high temperatures followed by rapid cooling. The observation that ferric iron in aluminosilicate glass is the source of bioavailable iron in coal fly ash suggests that particles from ambient sources and other specific combustion sources should be examined for the presence of this potential source of bioavailable iron.