Enzymatic mechanism of Fe-only hydrogenase: density functional study on H-H making/breaking at the diiron cluster with concerted proton and electron transfers

The mechanism of the enzymatic hydrogen bond forming/breaking (2H(+) + 2e<==>H(2)) and the plausible charge and spin states of the catalytic diiron subcluster [FeFe](H) of the H cluster in Fe-only hydrogenases are probed computationally by the density functional theory. It is found that the active center [FeFe](H) can be rationally simulated as [[H](CH(3)S)(CO)(CN(-))Fe(p)(CO(b))(mu-SRS)Fe(d)(CO)(CN(-))L], where the monovalence [H] stands for the [4Fe4S](H)(2+) subcluster bridged to the [FeFe](H) moiety, (CH(3)S) represents a Cys-S, and (CO(b)) represents a bridging CO. L could be a CO, H(2)O, H(-), H(2), or a vacant coordination site on Fe(d). Model structures of possible redox states are optimized and compared with the X-ray crystallographic structures and FTIR experimental data. On the basis of the optimal structures, we study the most favorable path of concerted proton transfer and electron transfer in H(2)-forming/breaking reactions at [FeFe](H). Previous mechanisms derived from quantum chemical computations of Fe-only hydrogenases (Cao, Z.; Hall, M. B. J. Am. Chem. Soc. 2001, 123, 3734; Fan, H.; Hall, M. B. J. Am. Chem. Soc. 2001, 123, 3828) involved an unidentified bridging residue (mu-SRS), which is either a propanedithiolate or dithiomethylamine. Our proposed mechanism, however, does not require such a ligand but makes use of a shuttle of oxidation states of the iron atoms and a reaction site between the two iron atoms. Therefore, the hydride H(b)(-) (bridged to Fe(p) and Fe(d)) and eta(2)-H(2) at Fe(p) or Fe(d) most possibly play key roles in the dihydrogen reversible oxidation at the [FeFe](H) active center. This suggested way of H(2) formation/splitting is reminiscent of the mechanism of [NiFe] hydrogenases and therefore would unify the mechanisms of the two related enzymes.     

Isocyanide in Biochemistry? A Theoretical Investigation of the Electronic Effects and Energetics of Cyanide Ligand Protonation in [FeFe]‐Hydrogenases

The presence of Fe‐bound cyanide ligands in the active site of the proton‐reducing enzymes [FeFe]‐hydrogenases has led to the hypothesis that such Brønsted–Lowry bases could be protonated during the catalytic cycle, thus implying that hydrogen isocyanide (HNC) might have a relevant role in such crucial microbial metabolic paths. We present a hybrid quantum mechanical/molecular mechanical (QM/MM) study of the energetics of CN^? protonation in the enzyme, and of the effects that cyanide protonation can have on [FeFe]‐hydrogenase active sites. A detailed analysis of the electronic properties of the models and of the energy profile associated with H₂ evolution clearly shows that such protonation is dysfunctional for the catalytic process. However, the inclusion of the protein matrix surrounding the active site in our QM/MM models allowed us to demonstrate that the amino acid environment was finely selected through evolution, specifically to lower the Brønsted–Lowry basicity of the cyanide ligands. In fact, the conserved hydrogen‐bonding network formed by these ligands and the neighboring amino acid residues is able to impede CN^? protonation, as shown by the fact that the isocyanide forms of [FeFe]‐hydrogenases do not correspond to stationary points on the enzyme QM/MM potential‐energy surface.     

Silicon–Heteroaromatic [FeFe] Hydrogenase Model Complexes: Insight into Protonation,Electrochemical Properties,and Molecular Structures

To learn from Nature how to create an efficient hydrogen‐producing catalyst, much attention has been paid to the investigation of structural and functional biomimics of the active site of [FeFe]‐hydrogenase. To understand their catalytic activities, the μ‐S atoms of the dithiolate bridge have been considered as possible basic sites during the catalytic processes. For this reason, a series of [FeFe]‐H₂ase mimics have been synthesized and characterized. Different [FeFe]‐hydrogenase model complexes containing bulky Si–heteroaromatic systems or fluorene directly attached to the dithiolate moiety as well as their mono‐PPh₃‐substituted derivatives have been prepared and investigated in detail by spectroscopic, electrochemical, X‐ray diffraction, and computational methods. The assembly of the herein reported series of complexes shows that the μ‐S atoms can be a favored basic site in the catalytic process. Small changes in the (hetero)‐aromatic system of the dithiolate moiety are responsible for large differences in their structures. This was elucidated in detail by DFT calculations, which were consistent with the experimental results.     

A third type of hydrogenase catalyzing H2 activation

The activation of molecular hydrogen is of interest both from a chemical and biological viewpoint. The covalent bond of H(2) is strong (436 kJ mol(-1)). Its cleavage is catalyzed by metals or metal complexes in chemical hydrogenation reactions and by metalloenzymes named hydrogenases in microorganisms. Until recently only two types of hydrogenases are known, the [FeFe[-hydrogenases and [NiFe[-hydrogenases. Both types, which are phylogenetically unrelated, harbor in their active site a dinuclear metal center with intrinsic CO and cyanide ligands and contain iron-sulfur clusters for electron transport as revealed by their crystal structures. Fifteen years ago a third type of phylogenetically unrelated hydrogenase was discovered, which has a mononuclear iron active site and is devoid of iron-sulfur clusters. It was initially referred to as "metal free" hydrogenase, but was later renamed iron-sulfur cluster-free hydrogenase or [Fe[-hydrogenase. In this review, we introduce first the [FeFe[-hydrogenases and [NiFe[-hydrogenases, and then focus on the structure and function of the iron-sulfur cluster-free hydrogenase (Hmd) and show that this enzyme contains an iron-containing cofactor. The low-spin iron is complexed by two intrinsic CO-, one sulfur- and one or two N/O ligands and has one open coordination site, which is proposed to be the location of H(2) binding.     

In silico evaluation of proposed biosynthetic pathways for the unique dithiolate ligand of the H-cluster of [FeFe]-hydrogenase

The biosynthesis of the active site of the [FeFe]-hydrogenases (H-cluster) remains a tantalizing puzzle due to its unprecedented and complex ligand environment. It contains a [2Fe] cluster ([2Fe](H)) bearing cyanide and carbon monoxide ligands attached to low-valence Fe ions and an abiological dithiolate ligand (SCH(2)XCH(2)S)(2-) that bridges the two iron centers. Various experimentally testable hypotheses have already been put forward regarding the precursor molecule and the biosynthetic mechanism that leads to the formation of the dithiolate ligand. In this work, we report a density functional theory-based theoretical evaluation of these hypotheses. We find preference for a mechanistically simple and energetically favorable pathway that includes known radical-SAM (S-adenosylmethionine) catalyzed reactions. We modeled this pathway using a long alkyl chain precursor molecule that leads to the formation of pronanadithiolate (X = CH(2)). However, the same pathway can be readily adopted for the biosynthesis of the dithiomethylamine (X = NH) or the dithiomethylether (X = O) analog, provided that the proper precursor molecule is available.     

Refining the active site structure of iron-iron hydrogenase using computational infrared spectroscopy

Iron-iron hydrogenases ([FeFe]H2ases) are exceptional natural catalysts for the reduction of protons to dihydrogen. Future biotechnological applications based on these enzymes require a precise understanding of their structures and properties. Although the [FeFe]H2ases have been characterized by single-crystal X-ray crystallography and a range of spectroscopic techniques, ambiguities remain regarding the details of the molecular structures of the spectroscopically observed forms. We use density functional theory (DFT) computations on small-molecule computational models of the [FeFe]H2ase active site to address this problem. Specifically, a series of structural candidates are geometry optimized and their infrared (IR) spectra are simulated using the computed C-O and C-N stretching frequencies and infrared intensities. Structural assignments are made by comparing these spectra to the experimentally determined IR spectra for each form. The H red form is assigned as a mixture of an Fe(I)Fe(I) form with an open site on the distal iron center and either a Fe(I)Fe(I) form in which the distal cyanide has been protonated or a Fe(II)Fe(II) form with a bridging hydride ligand. The Hox form is assigned as a valence-localized Fe(I)Fe(II) redox level with an open site at the distal iron. The Hox(air)(ox) form is assigned as an Fe(II)Fe(II) redox level with OH(-) or OOH(-) bound to the distal iron center that may or may not have an oxygen atom bound to one of the sulfur atoms of the dithiolate linker. Comparisons of the computed IR spectra of the (12)CO and (13)CO inhibited form with the experimental IR spectra show that exogenous CO binds terminally to the distal iron center.     

Comparing the electronic properties of the low-spin cyano-ferric [Fe(N4)(Cys)] active sites of superoxide reductase and p450cam using ENDOR spectroscopy and DFT calculations

Superoxide reductase (SOR) and P450 enzymes contain similar [Fe(N)4(SCys)] active sites and, although they catalyze very different reactions, are proposed to involve analogous low-spin (hydro)peroxo-Fe(III) intermediates in their respective mechanisms that can be modeled by cyanide binding. The equatorial FeN4 ligation by four histidine ligands in CN-SOR and the heme in CN-P450cam is directly compared by 14N ENDOR, while the axial Fe-CN and Fe-S bonding is probed by 13C ENDOR of the cyanide ligand and 1Hbeta ENDOR measurements to determine the spin density delocalization onto the cysteine sulfur. There are small, but notable, differences in the bonding between Fe(III) and its ligands in the two enzymes. The ENDOR measurements are complemented by DFT computations that support the semiempirical equation used to compute spin densities on metal-coordinated cysteinyl and shed light on bonding changes as the Fe-C-N linkage bends. They further indicate that H bonds to the cysteinyl thiolate sulfur ligand reduce the spin density on the sulfur in both active sites to a degree that exceeds the difference induced by the alternative sets of "in-plane" nitrogen ligands.     

Distinguishing Protonation States of Histidine Ligands to the Oxidized Rieske Iron–Sulfur Cluster through 15N Vibrational Frequency Shifts

The Rieske [2Fe–2S] cluster is a vital component of many oxidoreductases, including mitochondrial cytochrome bc1; its chloroplast equivalent, cytochrome b6f; one class of dioxygenases; and arsenite oxidase. The Rieske cluster acts as an electron shuttle and its reduction is believed to couple with protonation of one of the cluster′s His ligands. In cytochromes bc1 and b6f, for example, the Rieske cluster acts as the first electron acceptor in a modified Q cycle. The protonation states of the cluster′s His ligands determine its ability to accept a proton and possibly an electron through a hydrogen bond to the electron carrier, ubiquinol. Experimental determination of the protonation states of a Rieske cluster′s two His ligands by NMR spectroscopy is difficult, due to the close proximity of the two paramagnetic iron atoms of the cluster. Therefore, this work reports density functional calculations and proposes that difference vibrational spectroscopy with ¹⁵N isotopic substitution may be used to assign the protonation states of the His ligands of the oxidized Rieske [2Fe–2S] complex.     

Density functional study on dihydrogen activation at the H cluster in Fe-only hydrogenases

Models simulating the catalytic diiron subcluster [FeFe](H) in Fe-only hydrogenases have often been designed for computational exploration of the catalytic mechanism of the formation and cleavage of dihydrogen. In this work, we extended the above models by explicitly considering the electron reservoir [4Fe-4S](H) which is linked to the diiron subcluster to form a whole H cluster ([6Fe-6S] = [4Fe-4S](H) + [FeFe](H)). Large-scale density functional theory (DFT) computations on the complete H cluster, together with simplified models in which the [4Fe-4S](H) subcluster is not directly involved in the reaction processes, have been performed to probe hydrogen activation on the Fe-only hydrogenases. A new intermediate state containing an Fe(p)...H...CN two-electron three-center bond is identified as a key player in the H2 formation/cleavage processes.     

The electronic structure of the H-cluster in the [FeFe]-hydrogenase from Desulfovibrio desulfuricans: a Q-band 57Fe-ENDOR and HYSCORE study

The active site of the (57)Fe-enriched [FeFe]-hydrogenase (i.e., the "H-cluster") from Desulfovibrio desulfuricans has been examined using advanced pulse EPR methods at X- and Q-band frequencies. For both the active oxidized state (H(ox)) and the CO inhibited form (H(ox)-CO) all six (57)Fe hyperfine couplings were detected. The analysis shows that the apparent spin density extends over the whole H-cluster. The investigations revealed different hyperfine couplings of all six (57)Fe nuclei in the H-cluster of the H(ox)-CO state. Four large 57Fe hyperfine couplings in the range 20-40 MHz were found (using pulse ENDOR and TRIPLE methods) and were assigned to the [4Fe-4S](H) (cubane) subcluster. Two weak (57)Fe hyperfine couplings below 5 MHz were identified using Q-band HYSCORE spectroscopy and were assigned to the [2Fe](H) subcluster. For the H(ox) state only two different 57Fe hyperfine couplings in the range 10-13 MHz were detected using pulse ENDOR. An (57)Fe line broadening analysis of the X-band CW EPR spectrum indicated, however, that all six (57)Fe nuclei in the H-cluster are contributing to the hyperfine pattern. It is concluded that in both states the binuclear subcluster [2Fe](H) assumes a [Fe(I)Fe(II)] redox configuration where the paramagnetic Fe(I) atom is attached to the [4Fe-4S](H) subcluster. The (57)Fe hyperfine interactions of the formally diamagnetic [4Fe-4S](H) are due to an exchange interaction between the two subclusters as has been discussed earlier by Popescu and Münck [Popescu, C.V.; Münck, E., J. Am. Chem. Soc. 1999, 121, 7877-7884]. This exchange coupling is strongly enhanced by binding of the extrinsic CO ligand. Binding of the dihydrogen substrate may induce a similar effect, and it is therefore proposed that the observed modulation of the electronic structure by the changing ligand surrounding plays an important role in the catalytic mechanism of [FeFe]-hydrogenase.     

DFT investigation of structural, electronic, and catalytic properties of diiron complexes related to the [2Fe](H) subcluster of Fe-only hydrogenases

Hydrogenases catalyze the reversible oxidation of dihydrogen to protons and electrons. The structures of two Fe-only hydrogenases have been recently reported [Peters, J. W.; Lanzilotta, W. N.; Lemon, B. J.; Seefeldt, L. C. Science 1998, 282, 1853-1858. Nicolet, Y.; Piras, C.; Legrand, P.; Hatchikian, E. C.; Fontecilla-Camps, J. C. Structure 1999, 7, 13-23], showing that the likely site of dihydrogen activation is the so-called [2Fe](H) cluster, where each Fe ion is coordinated by CO and CN(-) ligands and the two metals are bridged by a chelating S-X(3)-S ligand. Moreover, the presence of a water molecule coordinated to the distal Fe2 center suggested that the Fe2 atom could be a suitable site for binding and activation of H(2). In this contribution, we report a density functional theory investigation of the structural and electronic properties of complexes derived from the [(CO)(CH(3)S)(CN)Fe(II)(mu-PDT)Fe(II)(CO)(2)(CN)](-1) species, which is related to the [2Fe](H) cluster observed in Fe-only hydrogenases. Our results show that the structure of the [2Fe](H) cluster observed in the enzyme does not correspond to a stable form of the isolated cluster, in the absence of the protein. As a consequence, the reactivity of [(CO)(CH(3)S)(CN)Fe(II)(mu-PDT)Fe(II)(CO)(2)(CN)](-1) derivatives in solution may be expected to be quite different from that of the active site of Fe-only hydrogenases. In fact, the most favorable path for H(2) activation involves the two metal atoms and one of the bridging S atoms and is associated with a very low activation energy (5.3 kcal mol(-1)). The relevance of these observations for the catalytic properties of Fe-only hydrogenases is discussed in light of available experimental and theoretical data.     

Role of the azadithiolate cofactor in models for [FeFe]-hydrogenase: novel structures and catalytic implications

This paper summarizes studies on the redox behavior of synthetic models for the [FeFe]-hydrogenases, consisting of diiron dithiolato carbonyl complexes bearing the amine cofactor and its N-benzyl derivative. Of specific interest are the causes of the low reactivity of oxidized models toward H(2), which contrasts with the high activity of these enzymes for H(2) oxidation. The redox and acid-base properties of the model complexes [Fe(2)[(SCH(2))(2)NR](CO)(3)(dppv)(PMe(3))](+) ([2](+) for R = H and [2'](+) for R = CH(2)C(6)H(5), dppv = cis-1,2-bis(diphenylphosphino)ethylene)) indicate that addition of H(2) followed by deprotonation are (i) endothermic for the mixed valence (Fe(II)Fe(I)) state and (ii) exothermic for the diferrous (Fe(II)Fe(II)) state. The diferrous state is shown to be unstable with respect to coordination of the amine to Fe, a derivative of which was characterized crystallographically. The redox and acid-base properties for the mixed valence models differ strongly for those containing the amine cofactor versus those derived from propanedithiolate. Protonation of [2'](+) induces disproportionation to a 1:1 mixture of the ammonium [H2'](+) (Fe(I)Fe(I)) and the dication [2'](2+) (Fe(II)Fe(II)). This effect is consistent with substantial enhancement of the basicity of the amine in the Fe(I)Fe(I) state vs the Fe(II)Fe(I) state. The Fe(I)Fe(I) ammonium compounds are rapid and efficient H-atom donors toward the nitroxyl compound TEMPO. The atom transfer is proposed to proceed via the hydride. Collectively, the results suggest that proton-coupled electron-transfer pathways should be considered for H(2) activation by the [FeFe]-hydrogenases.     

Comparative study of metal-porphyrins, -porphyrazines,and -phthalocyanines

A theoretical comparative study of complexes of porphyrin (P), porphyrazine (Pz), and phthalocyanine (Pc) with metal (M) = Fe, Co, Ni, Cu, and Zn has been carried out using a DFT method. The calculations provide a clear elucidation of the ground states for the MP/Pz/Pc molecules and for a series of [MP/Pz/Pc](x-) and [MP/Pz/Pc](y+) ions (x = 1, 2, 3, 4; y = 1, 2). There are significant differences among MP, MPz, and MPc in the electronic structure and other calculated properties. For FeP/Pz and CoP/Pz, the first oxidation occurs at the central metal, while it is the macroring of FePc and CoPc that is the site of oxidation. The smaller coordination cavity results in a stronger ligand field in Pz than in P. However, the benzo annulation produces a surprisingly strong destabilizing effect on the metal-macrocycle bonding. The effects of Cl axial bonding upon the electronic structures of the iron(III) complexes of P, Pz, and Pc were examined, as was the bonding of pyridine (py) to NiP, NiPz, and NiPc. The porphinato core size plays a crucial role in controlling the spin state of Fe(III) in these complexes. FePc(Cl) is predicted to be a pure intermediate-spin system, whereas NiPz(py)(2) and NiPc(py)(2) are metastable in high-spin (S = 1) states. The NiPz/Pc-(py)(2) binding energy curve has only a shallow well that facilitates decomposition of the complex. The NiP-(py)(2) bond energy is small, but the relatively deep well in the binding energy curve ought to make this system stable to decomposition.     

Cyanide Binding to [FeFe]-Hydrogenase Stabilizes the Alternative Configuration of the Proton Transfer Pathway

Hydrogenases are H₂ converting enzymes that harbor catalytic cofactors in which iron (Fe) ions are coordinated by biologically unusual carbon monoxide (CO) and cyanide (CN⁻) ligands. Extrinsic CO and CN⁻, however, inhibit hydrogenases. The mechanism by which CN⁻ binds to [FeFe]-hydrogenases is not known. Here, we obtained crystal structures of the CN⁻-treated [FeFe]-hydrogenase CpI from Clostridium pasteurianum. The high resolution of 1.39 Å allowed us to distinguish intrinsic CN⁻ and CO ligands and to show that extrinsic CN⁻ binds to the open coordination site of the cofactor where CO is known to bind. In contrast to other inhibitors, CN⁻ treated crystals show conformational changes of conserved residues within the proton transfer pathway which could allow a direct proton transfer between E279 and S319. This configuration has been proposed to be vital for efficient proton transfer, but has never been observed structurally.     

Effect of Cyanide Ligands on the Electronic Structure of [FeFe] Hydrogenase Active‐Site Model Complexes with an Azadithiolate Cofactor

A detailed characterization of a close synthetic model of the [2 Fe]_H subcluster in the [FeFe] hydrogenase active site is presented. It contains the full primary coordination sphere of the CO‐inhibited oxidized state of the enzyme including the CN^? ligands and the azadithiolate (adt) bridge, [((μ‐S? CH₂)₂NR)Fe₂(CO)₄(CN)₂]^2?, R=CH₂CH₂SCH₃. The electronic structure of the model complex in its Fe^IFe^II state was investigated by means of density functional theory (DFT) calculations and Fourier transform infrared (FTIR) spectroscopy. By using a combination of continuous‐wave (CW) electron paramagnetic resonance (EPR) and hyperfine sublevel correlation (HYSCORE) experiments as well as DFT calculations, it is shown that, for this complex, the spin density is delocalized over both iron atoms. Interestingly, we found that the nitrogen hyperfine coupling, which represents the interaction between the unpaired electron and the nitrogen at the dithiolate bridge, is slightly larger than that in the analogous complex in which the CN^? ligands are replaced with PMe₃ ligands. This reveals, first, that the CN^?/PMe₃ ligands coordinated to the iron core are electronically coupled to the amine in the adt bridge. Second, the CN^? ligands in this complex are somewhat stronger σ‐donor ligands than the PMe₃ ligand, and thereby enable more spin density to be transferred from the Fe core to the adt unit, which might in turn affect the reactivity of the bridging amine.     

Density functional calculations on the binding of dinitrogen to the FeFe cofactor in Fe-only nitrogenase: FeFeco(mu 6-N2) as intermediate in nitrogen fixation

The geometries and stabilities of the FeFe cofactor at different oxidation states and its complexes with N(2) have been determined by density functional calculations. These calculations support an EPR-inactive resting state of the FeFe cofactor with four Fe(2+) and four Fe(3+) sites (4Fe(2+)4Fe(3+)). FeFeco(mu(6)-N(2)) with a central dinitrogen ligand is predicted to be the most stable complex of the FeFe cofactor with N(2). It is easily formed by penetration of N(2) into the trigonal Fe(6) prism of the FeFe cofactor with an approximate barrier of 4 kcal mol(-1). The present DFT results suggest that an FeFeco(mu(6)-N(2)) entity is a plausible intermediate in dinitrogen fixation by nitrogenase. CO is calculated to bind even more strongly than N(2) to the FeFe cofactor so that CO may inhibit the reduction of nitrogen by Fe-only nitrogenase.     

Electronic Structure of an [FeFe] Hydrogenase Model Complex in Solution Revealed by X-ray Absorption Spectroscopy Using Narrow-Band Emission Detection

High-resolution X-ray absorption spectroscopy with narrow-band X-ray emission detection, supported by density functional theory calculations (XAES-DFT), was used to study a model complex, ([Fe(2)(μ-adt)(CO)(4)(PMe(3))(2)] (1, adt = S-CH(2)-(NCH(2)Ph)-CH(2)-S), of the [FeFe] hydrogenase active site. For 1 in powder material (1(powder)), in MeCN solution (1'), and in its three protonated states (1H, 1Hy, 1HHy; H denotes protonation at the adt-N and Hy protonation of the Fe-Fe bond to form a bridging metal hydride), relations between the molecular structures and the electronic configurations were determined. EXAFS analysis and DFT geometry optimization suggested prevailing rotational isomers in MeCN, which were similar to the crystal structure or exhibited rotation of the (CO) ligands at Fe1 (1(CO), 1Hy(CO)) and in addition of the phenyl ring (1H(CO,Ph), 1HHy(CO,Ph)), leading to an elongated solvent-exposed Fe-Fe bond. Isomer formation, adt-N protonation, and hydride binding caused spectral changes of core-to-valence (pre-edge of the Fe K-shell absorption) and of valence-to-core (K?(2,5) emission) electronic transitions, and of Kα RIXS data, which were quantitatively reproduced by DFT. The study reveals (1) the composition of molecular orbitals, for example, with dominant Fe-d character, showing variations in symmetry and apparent oxidation state at the two Fe ions and a drop in MO energies by ～1 eV upon each protonation step, (2) the HOMO-LUMO energy gaps, of ～2.3 eV for 1(powder) and ～2.0 eV for 1', and (3) the splitting between iron d(z(2)) and d(x(2)-y(2)) levels of ～0.5 eV for the nonhydride and ～0.9 eV for the hydride states. Good correlations of reduction potentials to LUMO energies and oxidation potentials to HOMO energies were obtained. Two routes of facilitated bridging hydride binding thereby are suggested, involving ligand rotation at Fe1 for 1Hy(CO) or adt-N protonation for 1HHy(CO,Ph). XAES-DFT thus enables verification of the effects of ligand substitutions in solution for guided improvement of [FeFe] catalysts.     

Structure and vibrational dynamics of model compounds of the [FeFe]-hydrogenase enzyme system via ultrafast two-dimensional infrared spectroscopy

Ultrafast two-dimensional infrared (2D) spectroscopy has been applied to study the structure and vibrational dynamics of (mu-S(CH2)3S)Fe2(CO)6, a model compound of the active site of the [FeFe]-hydrogenase enzyme system. Comparison of 2D-IR spectra of (mu-S(CH2)3S)Fe2(CO)6 with density functional theory calculations has determined that the solution-phase structure of this molecule is similar to that observed in the crystalline phase and in good agreement with gas-phase simulations. In addition, vibrational coupling and rapid (<5 ps) solvent-mediated equilibration of energy between vibrationally excited states of the carbonyl ligands of the di-iron-based active site model are observed prior to slower (approximately 100 ps) relaxation to the ground state. These dynamics are shown to be solvent-dependent and form a basis for the future determination of the vibrational interactions between active site and protein.     

A theoretical study on the reaction pathways of peroxynitrite formation and decay at nonheme iron centers

A computational study based on density functional theory was undertaken to identify possible reaction pathways for the formation and decomposition of peroxynitrite at models of the active sites of the nonheme superoxide scavenging enzymes superoxide reductase (SOR) and iron superoxide dismutase (FeSOD). Two peroxynitrite isomers and their possible protonated states were investigated, namely Fe? OONO^?, Fe? N(O)OO^?, Fe? OONOH, and Fe? N(O)OOH. Peroxynitrite formation at the active sites was assumed by either the interaction of a peroxynitrite cis/trans anion with the pentacoordinated iron active site or the interaction between a nitric oxide bound adduct and superoxide; both scenarios were found to be facile for all models investigated. The ferrous adducts of the Fe? OONO^?isomer were found to undergo instant heterolytic cleavage of the O? ONO bond to yield nitrite, whereas for the ferric adducts, the homolytic cleavage of the O? ONO bond to yield nitrogen dioxide was found to be energetically facile. For the Fe? N(O)OO^? isomer, the active site models of FeSOD and SOR were only able to accommodate the cis isomer of peroxynitrite. Ferric adducts of the cis Fe? OONO^? isomer were found to be energetically more stable than their trans counterparts and were also more stable than the cis adducts of the Fe? N(O)OO^? isomer; conversely, the protonated forms of all adducts of the Fe? OONOH isomer were found to be lower in energy than their equivalent Fe? N(O)OOH adducts. Multiple reaction pathways for the decomposition of the formed peroxynitrite adducts (whether the anions or the protonated forms) were proposed and explored. The energy requirements for the decomposition processes ranged from exothermic to highly demanding depending on the peroxynitrite isomer, the type of model (whether an SOR or FeSOD active site), and the oxidation state of iron. © 2014 Wiley Periodicals, Inc.     

How bridging ligands and neighbouring groups tune the gold-gold bond strength

Gold-gold interactions in small polynuclear complexes are analysed using extended Hückel calculations. They are influenced by the nature of the ligand donor atoms, by the bridging ligands, but most by the formal oxidation state of the metal. Au---Au bonds are much stronger in complexes of Au(II) and Au(III), but a weak interaction between two d¹⁰ centres exists for Au(I) complexes, owing to mixing of the s and p orbitals with the d orbitals. Phosphines induce stronger metal-metal bonds when coordinated trans to the Au---Au bond in [Au(II)[(CH₂)₂PPh₂]L]₂ (Ph = phenyl), but have the opposite effect when bonded orthogonally to the metal-metal axis in Au(I) binuclear species. When two gold atoms are bridged by a single carbon atom, belonging either to mesityl (Mes = 2,4,6-Me₃C₆H₂) or CR₂, the former produces stronger Au(I)---Au(I) interactions, reflected in shorter distances. Formal oxidation states are proposed for the gold atoms in two mixed-valence clusters, [Au4(C₆F₅)₂((PPh₃)_{2CH})2(PPh3)2](ClO4)2 and [{(2,4,6-C6F3H2)Au(CH2PPh2CH2)2Au{in2}-Au(CH₂PPh₂CH₂)₂Au](ClO₄)₂. The results suggest a higher oxidation state for the outer gold atoms, in both the T-shaped tetranuclear cluster and the Au₆ linear chain.