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Journal of computational chemistry, 2011
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 (SCH2XCH2S)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 = CH2). 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. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Journal of Biological Inorganic Chemistry, 2010
FeFe hydrogenases [1] catalyze the reversible oxidation of dihydrogen at a remarkable rate [2, 3]. Their active site, termed the H-cluster, comprises a classic [4Fe-4S] cubane that is covalently linked via a bridging cysteine residue to a biologically unprecedented organometallic binuclear 2Fesubcluster. The two clusters are electronically [4] and magnetically [5] inseparable. The low-spin and lowvalence iron centers of the 2Fe-subcluster are stabilized by diatomic carbonyl (CO) and cyanide (CN -) strong-field ligands and they are bridged by a dithiolate group (SCH 2 XCH 2 S) 2-, whose central atom (bridgehead) has not yet been unequivocally determined. On the basis of X-ray crystallography, Fourier transform IR spectroscopy, 14 N hyperfine sublevel correlation spectroscopy, and theoretical calculations, the dithiolate ligand has been proposed to be 1,3-propanedithiolate (PDT; X is CH 2 ) [6], dithiomethylamine (DTMA; X is NH) [7, 8], or dithiomethyl ether (DTME; X is O) [9].
Journal of the American Chemical Society, 2010
The report 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 and 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-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, as indicated by the reaction of [HFe 2 [(SCH 2 ) 2 NH](CO) 2 (dppv) 2 ] + with TEMPO. Collectively, the results suggest that proton-coupled electron-transfer pathways should be considered for H 2 activation by the [FeFe]-hydrogenases. rauchfuz@illinois.edu. Supporting Information Available: Crystallographic information file (cif) for [2′(MeCN)](BF 4 ) 2 , thermodynamic calculations, and associated spectra.
Chelate Control of Diiron(I) Dithiolates Relevant to the [Fe−Fe]- Hydrogenase Active Site
Inorganic Chemistry, 2007
The reaction of Fe 2 (S 2 C 2 H 4 )(CO) 6 with cis-Ph 2 PCH=CHPPh 2 (dppv) yields Fe 2 (S 2 C 2 H 4 ) (CO) 4 (dppv), 1(CO) 4 , wherein the dppv ligand is chelated to a single iron center. NMR analysis indicates that in 1(CO) 4 , the dppv ligand spans axial and basal coordination sites. In addition to the axial-basal isomer, the 1,3-propanedithiolate and azadithiolate derivatives exist as dibasal isomers. Density functional theory (DFT) calculations indicate that the axial-basal isomer is destabilized by nonbonding interactions between the dppv and the central NH or CH 2 of the larger dithiolates. The Fe(CO) 3 subunit in 1(CO) 4 undergoes substitution with PMe 3 and cyanide to afford 1(CO) 3 (PMe 3 ) and (Et 4 N)[1(CN)(CO) 3 ], respectively. Kinetic studies show that 1(CO) 4 reacts faster with donor ligands than does its parent Fe 2 (S 2 C 2 H 4 )(CO) 6 . The rate of reaction of 1(CO) 4 with PMe 3 was first order in each reactant, k = 3.1 × 10 − 4 M −1 s −1 . The activation parameters for this substitution reaction, ΔH ‡ = 5.8(5) kcal/mol and ΔS ‡ = −48(2) cal/deg·mol, indicate an associative pathway. DFT calculations suggest that, relative to Fe 2 (S 2 C 2 H 4 )(CO) 6 , the enhanced electrophilicity of 1(CO) 4 arises from the stabilization of a "rotated" transition state, which is favored by the unsymmetrically disposed donor ligands. Oxidation of MeCN solutions of 1(CO) 3 (PMe 3 )
Synthesis of the 2Fe subcluster of the [FeFe]-hydrogenase H cluster on the HydF scaffold
Proceedings of the National Academy of Sciences, 2010
The organometallic H cluster at the active site of [FeFe]-hydrogenase consists of a 2Fe subcluster coordinated by cyanide, carbon monoxide, and a nonprotein dithiolate bridged to a [4Fe-4S] cluster via a cysteinate ligand. Biosynthesis of this cluster requires three accessory proteins, two of which (HydE and HydG) are radical S-adenosylmethionine enzymes. The third, HydF, is a GTPase. We present here spectroscopic and kinetic studies of HydF that afford fundamental new insights into the mechanism of H-cluster assembly. Electron paramagnetic spectroscopy reveals that HydF binds both [4Fe-4S] and [2Fe-2S] clusters; however, when HydF is expressed in the presence of HydE and HydG (HydF EG ), only the [4Fe-4S] cluster is observed by EPR. Insight into the fate of the [2Fe-2S] cluster harbored by HydF is provided by FTIR, which shows the presence of carbon monoxide and cyanide ligands in HydF EG . The thorough kinetic characterization of the GTPase activity of HydF shows that activity can be gated by monovalent cations and further suggests that GTPase activity is associated with synthesis of the 2Fe subcluster precursor on HydF, rather than with transfer of the assembled precursor to hydrogenase. Interestingly, we show that whereas the GTPase activity is independent of the presence of the FeS clusters on HydF, GTP perturbs the EPR spectra of the clusters, suggesting communication between the GTP-and cluster-binding sites. Together, the results indicate that the 2Fe subcluster of the H cluster is synthesized on HydF from a [2Fe-2S] cluster framework in a process requiring HydE, HydG, and GTP.
Explorations of iron-iron hydrogenase active site models by experiment and theory
2006
This dissertation describes computational and experimental studies of synthetic complexes that model the active site of the iron-iron hydrogenase [FeFe]H 2 ase enzyme. Simple dinuclear iron dithiolate complexes act as functional models of the ironiron hydrogenase enzyme by catalyzing isotopic exchange in D 2 /H 2 O mixtures. Density Functional Theory (DFT) calculations and new experiments have been performed that suggest reasonable mechanistic explanations for this reactivity. Evidence for the existence of an acetone derivative of the di-iron complex, as suggested by theory, is presented. Bis-phosphine substituted dinuclear iron dithiolate complexes react with the electrophilic species, H + and Et + (Et + = CH 3 CH 2 +) with differing regioselectivity; H + reacts to form a 3c-2e-Fe-H-Fe bond, while Et + reacts to form a new C-S bond. The instability of a bridging ethyl complex is attributed to the inability of the ethyl group, in contrast to a hydride, to form a stable 3c-2ebond with the two iron centers. Gas-phase density functional theory calculations are used to predict the solutionphase infrared spectra for a series of CO and CN-containing dinuclear iron complexes dithiolate. It is shown that simple linear scaling of the computed CO and C-N stretching iv frequencies yields accurate predictions of the experimentally determined ν(CO) and ν(CN) values. An N-heterocyclic carbene containing [FeFe]H 2 ase model complex, whose X-ray structure displays an apical carbene, is shown to undergo an unexpected simultaneous two-electron reduction. DFT shows, in addition to a one-electron Fe-Fe reduction, that the aryl-substituted N-heterocyclic carbene can accept a second electron more readily than the Fe-Fe manifold. The juxtaposition of these two one-electron reductions resembles the [FeFe]H 2 ase active site with an FeFe di-iron unit joined to the electroactive 4Fe4S cluster. Simple synthetic di-iron dithiolate complexes synthesized to date fail to reproduce the precise orientation of the diatomic ligands about the iron centers that is observed in the molecular structure of the reduced form of the enzyme active site. Herein, DFT computations are used for the rational design of synthetic complexes as accurate structural models of the reduced form of the enzyme active site. v DEDICATION This dissertation is dedicated to my great aunt Estile Williams and to the memory of my beloved grandmother Eva Harp.