| 1. |
- Bruschi, Maurizio, et al.
(författare)
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Functionally Relevant Interplay between the Fe(4)S(4) Cluster and CN(-) Ligands in the Active Site of [FeFe]-Hydrogenases.
- 2010
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 132:14, s. 4992-4992
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Tidskriftsartikel (refereegranskat)abstract
- [FeFe]-hydrogenases are highly efficient H(2)-evolving metalloenzymes that include cyanides and carbonyls in the active site. The latter is an Fe(6)S(6) cluster (the so-called H-cluster) that can be subdivided into a binuclear portion carrying the CO and CN(-) groups and a tetranuclear subcluster. The fundamental role of cyanide ligands in increasing the basicity of the H-cluster has been highlighted previously. Here a more subtle but crucial role played by the two CN(-) ligands in the active site of [FeFe]-hydrogenases is disclosed. In fact, QM/MM calculations on all-atom models of the enzyme from Desulfovibrio desulfuricans show that the cyanide groups fine-tune the electronic and redox properties of the active site, affecting both the protonation regiochemistry and electron transfer between the two subclusters of the H-cluster. Despite the crucial role of cyanides in the protein active site, the currently available bioinspired electrocatalysts generally lack CN(-) groups in order to avoid competition between the latter and the catalytic metal centers for proton binding. In this respect, we show that a targeted inclusion of phosphine ligands in hexanuclear biomimetic clusters may restore the electronic and redox features of the wild-type H-cluster.
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| 2. |
- Greco, Claudio, et al.
(författare)
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Fast Generation of Broken-Symmetry States in a Large System Including Multiple Iron-Sulfur Assemblies: Investigation of QM/MM Energies, Clusters Charges, and Spin Populations
- 2011
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Ingår i: International Journal of Quantum Chemistry. - : Wiley. - 0020-7608. ; 111:14, s. 3949-3960
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Tidskriftsartikel (refereegranskat)abstract
- A density functional theory study is presented regarding the energetics and the Mulliken population analyses of a quantum mechanical/molecular mechanical (QM/MM) system including multiple iron-sulfur clusters in the QM region. The [FeFe]-hydrogenase from Desulfovibrio desulfuricans was studied, and both the active site (an Fe6S6 assembly generally referred to as the H-cluster) and an ancillary Fe4S4 site were treated at the BP86-RI/TZVP level. The antiferromagnetic coupling that characterizes both sites was modeled using the broken-symmetry (BS) approach. For such a QM system, 36 different BS couplings can be defined, depending on the localization of spin excess on the various spin centers. All the BS states were obtained by means of an effective and simple method for spin localization, that is here described and compared with more sophisticated approaches already available in literature. The variation of the QM/MM energy among the various geometry-optimized protein models was found to be less than 25 kJ mol(-1). This energy variation almost doubles if no geometry optimization is performed. A detailed analysis of the additive nature of these variations in QM/MM energy is reported. The Mulliken charges show very small variations among the 36 BS states, whereas the Mulliken spin populations were found to be somewhat more variable. The relevance of such variations is discussed in light of the available Mossbauer and Electron Paramagnetic Resonance (EPR) spectroscopic data for the enzyme. Finally, the influence of the basis set on the spin populations, charges, and structural parameters of the models was investigated, by means of QM/MM computations on the same system at the BP86-RI/SVP level. (C) 2010 Wiley Periodicals, Inc. Int J Quantum Chem 111: 3949-3960, 2011
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| 3. |
- Greco, Claudio, et al.
(författare)
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Isocyanide in Biochemistry? A Theoretical Investigation of the Electronic Effects and Energetics of Cyanide Ligand Protonation in [FeFe]-Hydrogenases
- 2011
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Ingår i: Chemistry: A European Journal. - : Wiley. - 1521-3765 .- 0947-6539. ; 17:6, s. 1954-1965
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Tidskriftsartikel (refereegranskat)abstract
- 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 Bronsted-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 H-2 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 Bronsted-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.
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| 4. |
- Greco, Claudio, et al.
(författare)
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Magnetic Properties of [FeFe]-Hydrogenases: A Theoretical Investigation Based on Extended QM and QM/MM Models of the H-Cluster and Its Surroundings
- 2011
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Ingår i: European Journal of Inorganic Chemistry. - : Wiley. - 1099-0682 .- 1434-1948. ; :7, s. 1043-1049
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Tidskriftsartikel (refereegranskat)abstract
- In the present contribution, we report a theoretical investigation of the magnetic properties of the dihydrogen-evolving enzyme [FeFe]-hydrogenase, based on both DFT models of the active site (the H-cluster, a Fe6S6 assembly including a binuclear portion directly involved in substrates binding), and QM/MM models of the whole enzyme. Antiferromagnetic coupling within the H-cluster has been treated using the broken-symmetry approach, along with the use of different density functionals. Results of g value calculations turned out to vary as a function of the level of theory and of the extension of the model. The choice of the broken-symmetry coupling scheme also had a significant influence on the calculated g values, for both the active-ready (H-ox) and the CO-inhibited (H-ox-CO) enzyme forms. However, hyper-fine coupling-constant calculations were found to provide more consistent results. This allowed us to show that the experimentally detected delocalization of an unpaired electron at the binuclear subcluster in Desulfovibrio desulfuricans Hox is compatible with a weak interaction between the catalytic centre and a low-weight exogenous ligand like a water molecule.
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| 5. |
- Greco, Claudio, et al.
(författare)
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Mechanistic and Physiological Implications of the Interplay among Iron-Sulfur Clusters in [FeFe]-Hydrogenases. A QM/MM Perspective
- 2011
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 133:46, s. 18742-18749
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Tidskriftsartikel (refereegranskat)abstract
- Key stereoelectronic properties of Desulfovibrio desulfuricans [FeFe]-hydrogenase (DdH) were investigated by quantum mechanical description of its complete inorganic core, which includes a Fe6S6 active site (the H-cluster), as well as two ancillary Fe4S4 assemblies (the F and F' clusters). The partially oxidized, active-ready form of DdH is able to efficiently bind dihydrogen, thus starting H-2 oxidation catalysis. The calculations allow us to unambiguously assign a mixed Fe(H)Fe(I) state to the catalytic core of the active-ready enzyme and show that H-2 uptake exerts subtle, yet crucial influences on the redox properties of DdH. In fact, H-2 binding can promote electron transfer from the H-cluster to the solvent-exposed F'-cluster, thanks to a 50% decrease of the energy gap between the HOMO (that is localized on the H-cluster) and the LUMO (which is centered on the F'-cluster). Our results also indicate that the binding of the redox partners of DdH in proximity of its F'-cluster can trigger one-electron oxidation of the H-2-bound enzyme, a process that is expected to have an important role in H-2 activation. Our findings are analyzed not only from a mechanistic perspective, but also in consideration of the physiological role of DdH. In fact, this enzyme is known to be able to catalyze both the oxidation and the evolution of H-2, depending on the cellular metabolic requirements. Hints for the design of targeted mutations that could lead to the enhancement of the oxidizing properties of DdH are proposed and discussed.
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| 6. |
- Greco, Claudio, et al.
(författare)
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Probing the Effects of One-Electron Reduction and Protonation on the Electronic Properties of the Fe-S Clusters in the Active-Ready Form of [FeFe]-Hydrogenases. A QM/MM Investigation.
- 2011
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Ingår i: ChemPhysChem. - : Wiley. - 1439-7641 .- 1439-4235. ; 12:17, s. 3376-3382
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Tidskriftsartikel (refereegranskat)abstract
- A QM/MM investigation of the active-ready (Hox) form of [FeFe]-hydrogenase from D. desulfuricans, in which the electronic properties of all Fe-S clusters (H, F and F') have been simultaneously described using DFT, was carried out with the aim of disclosing a possible interplay between the H-cluster and the accessory iron-sulfur clusters in the initial steps of the catalytic process leading to H2 formation. It turned out that one-electron addition to the active-ready form leads to reduction of the F'-cluster and not of the H-cluster. Protonation of the H-cluster in Hox is unlikely, and in any case it would not trigger electron transfer from the accessory Fe4S4 clusters to the active site. Instead, one-electron reduction and protonation of the active-ready form trigger electron transfer within the protein, a key event in the catalytic cycle. In particular, protonation of the H-cluster after one-electron reduction of the enzyme lowers the energy of the lowest unoccupied molecular orbitals localized on the H-cluster to such an extent that a long-range electron transfer from the F'-cluster towards the H-cluster itself is allowed.
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| 7. |
- Heims, Florian, et al.
(författare)
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Synthesis and Spectroscopic Characterisation of a Heterodinuclear Iron(III)-Copper(II) Complex Based on an Asymmetric Dinucleating Ligand System
- 2012
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Ingår i: European Journal of Inorganic Chemistry. - : Wiley. - 1099-0682 .- 1434-1948. ; :29, s. 4565-4569
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Tidskriftsartikel (refereegranskat)abstract
- The site-directed generation of a heterodinuclear FeIIICuII complex by using a new asymmetric dinucleating ligand FloH is reported. The iron(III) ion is introduced first on the preferential metal-binding site of the ligand that leads to the formation of the thermodynamically favored five-membered chelate rings upon metal-binding. Copper(II) is introduced in the next step. The stepwise metalation strategy reported here may be extended to the preparation of other heterometallic complexes with the view of avoiding a statistical distribution. Such complexes can offer novel spectroscopic properties, electronic structures, and reactivities in comparison to their homometallic analogues.
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| 8. |
- Ryde, Ulf, et al.
(författare)
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Quantum refinement of [FeFe] hydrogenase indicates a dithiomethylamine ligand
- 2010
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 132:13, s. 4512-4512
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Tidskriftsartikel (refereegranskat)abstract
- The active site of the [FeFe] hydrogenases contains two Fe ions bound to one Cys ligand, three CO molecules, two CN(-) ions, and a dithiolate ligand. The nature of the last of these has been much discussed, and it has been suggested that it contains C, N, or O as the bridgehead atom. Most experimental studies indicate a N atom, whereas a recent density functional theory (DFT) study of a crystal structure indicated an O atom. Here, we performed quantum refinement on the same crystal structure with five different models of the dithiolate ligand X(CH(2)S(-))(2), with X = CH(2), NH(2)(+), NH (two conformations), or O; we found that structures with a N bridgehead atom actually provide the best fit to the raw crystallographic data. Quantum refinement is standard crystallographic refinement in which the molecular mechanics force field normally used to supplement the experimental raw data to give a more chemical structure is replaced by more accurate DFT calculations for the active site. Thereby, we obtain structures that are an ideal compromise between DFT and crystallography.
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| 9. |
- Yu, Lian, et al.
(författare)
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Targeting Intermediates of [FeFe]-Hydrogenase by CO and CN Vibrational Signatures
- 2011
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 1520-510X .- 0020-1669. ; 50:9, s. 3888-3900
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we employ density functional theory to assign vibrational signatures of [FeFe]-hydrogenase intermediates to molecular structures. For this purpose, we perform an exhaustive analysis of structures and harmonic vibrations of a series of CN and CO containing model clusters of the [FeFe]-hydrogenase enzyme active site considering also different charges, counterions, and solvents. The pure density functional BP86 in combination with a triple-xi polarized basis set produce reliable molecular structures as well as harmonic vibrations. Calculated CN and CO stretching vibrations are analyzed separately. Scaled vibrational frequencies are then applied to assign intermediates,in [FeFe]-hydrogenase's reaction cycle. The. " results nicely complement the previous studies of Darensbourg and The infrared spectrum of the H-ox form is in very good agreement with the calculated Spectrum of the (FeFeII)-Fe-I-model complex featuring a free coordination site at the distal Fe atom, as well as, With the calculated spectra of the complexes in which H-2 or H2O are coordinated at this site The spectrum of H-red measured from Desulfovibrio desulfuricans is compatible with a mixture of a (FeFeI)-Fe-I species with all terminal COs, and a (FeFeI)-Fe-I species with protonated dtma ligand, while the spectrum of H-red recently measured from Chlamydomonas reinhardtii is compatible with a mixture of a (FeFeI)-Fe-I species with a bridged CO, and a (FeFeII)-Fe-II species with a terminal hydride bound to the Fe atom.
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