Terminal ligand influence on the electronic structure and intrinsic redox properties of the [Fe4S4]2+ cubane clusters

We used photoelectron spectroscopy (PES) to study how the terminal ligands influence the electronic structure and redox properties of the [4Fe-4S] cubane in several series of ligand-substituted analogue complexes: [Fe(4)S(4)Cl(4-x)(CN)(x)](2-), [Fe(4)S(4)Cl(4-x)(SCN)(x)](2-), [Fe(4)S(4)Cl(4-x)(OAc)(x)](2-), [Fe(4)S(4)(SC(2)H(5))(4-x)(OPr)(x)](2-), and [Fe(4)S(4)(SC(2)H(5))(4-x)Cl(x)](2-) (x = 0-4). All the ligand-substituted complexes gave similar PES spectral features as the parents, suggesting that the mixed-ligand coordination does not perturb the electronic structure of the cubane core significantly. The terminal ligands, however, have profound effects on the electron binding energies of the cubane and induce significant shifts of the PES spectra, increasing in the order SC(2)H(5)(-) --> Cl(-) --> OAc(-)/OPr(-) --> CN(-) --> SCN(-). A linear relationship between the electron binding energies and the substitution number x was observed for each series, indicating that each ligand contributes independently and additively to the total binding energy. The electron binding energies of the gaseous complexes represent their intrinsic oxidation energies; the observed linear dependence on x is consistent with similar observations on the redox potentials of mixed-ligand cubane complexes in solution. The current study reveals the electrostatic nature of the interaction between the [4Fe-4S] cubane core and its coordination environment and provides further evidence for the electronic and structural stability of the cubane core and its robustness as a structural and functional unit in Fe-S proteins.     

Probing the intrinsic electronic structure of the cubane [4Fe-4S] cluster: nature's favorite cluster for electron transfer and storage

The cubane [4Fe-4S] is the most common multinuclear metal center in nature for electron transfer and storage. Using electrospray, we produced a series of gaseous doubly charged cubane-type complexes, [Fe4S4L4]2- (L = -SC2H5, -SH, -Cl, -Br, -I) and the Se-analogues [Fe4Se4L4]2- (L = -SC2H5, -Cl), and probed their electronic structures with photoelectron spectroscopy and density functional calculations. The photoelectron spectral features are similar among all the seven species investigated, revealing a weak threshold feature due to the minority spins on the Fe centers and confirming the low-spin two-layer model for the [4Fe-4S](2+) core and its "inverted level scheme". The measured adiabatic detachment energies, which are sensitive to the terminal ligand substitution, provide the intrinsic oxidation potentials of the [Fe4S4L4]2- complexes. The calculations revealed a simple correlation between the electron donor property of the terminal thiolate as well as the bridging sulfide with the variation of the intrinsic redox potentials. Our data provide intrinsic electronic structure information of the [4Fe-4S] cluster and the molecular basis for understanding the protein and solvent effects on the redox properties of the [4Fe-4S] active sites.     

Reactions of synthetic [2Fe-2S] and [4Fe-4S] clusters with nitric oxide and nitrosothiols

The interaction of nitric oxide (NO) with iron-sulfur cluster proteins results in degradation and breakdown of the cluster to generate dinitrosyl iron complexes (DNICs). In some cases the formation of DNICs from such cluster systems can lead to activation of a regulatory pathway or the loss of enzyme activity. In order to understand the basic chemistry underlying these processes, we have investigated the reactions of NO with synthetic [2Fe-2S] and [4Fe-4S] clusters. Reaction of excess NO(g) with solutions of [Fe2S2(SR)4](2-) (R = Ph, p-tolyl (4-MeC6H4), or 1/2 (CH2)2-o-C6H4) cleanly affords the respective DNIC, [Fe(NO)2(SR)2](-), with concomitant reductive elimination of the bridging sulfide ligands as elemental sulfur. The structure of (Et4N)[Fe(NO)2(S-p-tolyl)2] was verified by X-ray crystallography. Reactions of the [4Fe-4S] clusters, [Fe4S4(SR)4](2-) (R = Ph, CH2Ph, (t)Bu, or 1/2 (CH2)-m-C6H4) proceed in the absence of added thiolate to yield Roussin's black salt, [Fe4S3(NO)7](-). In contrast, (Et4N)2[Fe4S4(SPh)4] reacts with NO(g) in the presence of 4 equiv of (Et4N)(SPh) to yield the expected DNIC. For all reactions, we could reproduce the chemistry effected by NO(g) with the use of trityl-S-nitrosothiol (Ph3CSNO) as the nitric oxide source. These results demonstrate possible pathways for the reaction of iron-sulfur clusters with nitric oxide in biological systems and highlight the importance of thiolate-to-iron ratios in stabilizing DNICs.     

Antibacterial activity of [1Fe-2S]- and [2Fe-2S]-nitrosyl complexes as nitric oxide donors

Russian Chemical Bulletin - The biological activity of a series of sulfur-nitrosyl iron complexes (NICs) depends on the structure of the ligands and the position of the functional groups in the...     

[MoFe3S4]3+ and [MoFe3S4]2+ cubane clusters containing a pentamethylcyclopentadienyl molybdenum moiety

A series of organometallic molybdenum/iron/sulfur clusters of the general formula [Cp¹MoFe₃S₄L_n]^m (Cp¹ = η⁵-C₅Me₅; L = S^tBu, SPh, Cl, I, n = 3, m = 1−; L_n = I₂(P^tBu₃), m = 0; L = 2,6-diisopropylphenylisocyanide (ArNC), n = 7, m = 1+) have been synthesized. A cubane cluster (PPh₄)[Cp¹MoFe₃S₄(S^tBu)₃] (2) was isolated from a self-assembly reaction of Cp¹Mo(S^tBu)₃ (1), FeCl₃, LiS^tBu, and S₈ followed by cation exchange with PPh₄Br in CH₃CN, while an analogous cluster (PPh₄)[Cp¹MoFe₃S₄(SPh)₃] (3) was obtained from the Cp¹MoCl₄/FeCl₃/LiSPh/PPh₄Br reaction system or from a ligand substitution reaction of 2 with PhSH. Treatment of 2 with benzoyl chloride gave rise to (PPh₄)[Cp¹MoFe₃S₄Cl₃] (4), which was in turn converted to (PPh₄)[Cp¹MoFe₃S₄I₃] (5) by the reaction with NaI. A neutral cubane cluster Cp¹MoFe₃S₄I₂(P^tBu₃) (6) was generated upon treating 5 with P^tBu₃. Although reduction of 4 by cobaltocene under the presence of ArNC resulted in a disproportionation of the cubane core to give Fe₄S₄(ArNC)₉Cl (7), a similar reduction reaction of 5 produced [Cp¹MoFe₃S₄(ArNC)₇]I (8), where the MoFe₃S₄ core was retained. The crystal structures of 4–6, and 8 were determined by the X-ray analysis.     

Sequential oxidation of the cubane [4Fe--4S] cluster from [4Fe--4S](-) to [4Fe--4S](3+) in Fe(4)S(4)L(n)(-) complexes

Gaseous Fe(4)S(n)(-) (n = 4-6) clusters and synthetic analogue complexes, Fe(4)S(4)L(n)(-) (L = Cl, Br, I; n = 1-4), were produced by laser vaporization of a solid Fe/S target and electrospray from solution samples, respectively, and their electronic structures were probed by photoelectron spectroscopy. Low binding energy features derived from minority-spin Fe 3d electrons were clearly distinguished from S-derived bands. We showed that the electronic structure of the simplest Fe(4)S(4)(-) cubane cluster can be described by the two-layer spin-coupling model previously developed for the [4Fe] cubane analogues. The photoelectron data revealed that each extra S atom in Fe(4)S(5)(-) and Fe(4)S(6)(-) removes two minority-spin Fe 3d electrons from the [4Fe--4S] cubane core and each halogen ligand removes one Fe 3d electron from the cubane core in the Fe(4)S(4)L(n)(-) complexes, clearly revealing a behavior of sequential oxidation of the cubane over five formal oxidation states: [4Fe--4S](-) --> [4Fe--4S](0) --> [4Fe--4S](+) --> [4Fe-4S](2+) --> [4Fe-4S](3+). The current work shows the electron-storage capability of the [4Fe--4S] cubane, contributes to the understanding of its electronic structure, and further demonstrates the robustness of the cubane as a structural unit and electron-transfer center.     

Studies of inhibitor binding to the [4Fe-4S] cluster of quinolinate synthase

Stop for NadA! A [4Fe-4S] enzyme, NadA, catalyzes the formation of quinolinic acid in de?novo nicotinamide adenine dinucleotide (NAD) biosynthesis. A structural analogue of an intermediate, 4,5-dithiohydroxyphthalic acid (DTHPA), has an in?vivo NAD biosynthesis inhibiting activity in E. coli. The inhibitory effect can be explained by the coordination of DTHPA thiolate groups to a unique Fe site of the NadA [4Fe-4S] cluster.     

Electronic structure and intrinsic redox properties of [2Fe-2S]+ clusters with tri- and tetracoordinate iron sites

Using potentially bidentate ligands (-SC2H4NH2), we produced [2Fe-2S]+ species of different coordination geometries by fission of [4Fe-4S]2+ complexes. Even though the ligands are monodentate in the cubane complexes, both mono- and bidentate complexes were observed in the [2Fe] fission products through self-assembly because of the high reactivity of the tricoordinate iron sites. The electronic structure of the [2Fe] species was probed using photoelectron spectroscopy and density functional calculations. It was found that tetracoordination significantly decreases the electron binding energies of the [2Fe] complexes, thus increasing the reducing capability of the [2Fe-2S]+ clusters.     

Mechanistic insight into the nitrosylation of the [4Fe-4S] cluster of WhiB-like proteins

The reactivity of protein bound iron-sulfur clusters with nitric oxide (NO) is well documented, but little is known about the actual mechanism of cluster nitrosylation. Here, we report studies of members of the Wbl family of [4Fe-4S] containing proteins, which play key roles in regulating developmental processes in actinomycetes, including Streptomyces and Mycobacteria, and have been shown to be NO responsive. Streptomyces coelicolor WhiD and Mycobacterium tuberculosis WhiB1 react extremely rapidly with NO in a multiphasic reaction involving, remarkably, 8 NO molecules per [4Fe-4S] cluster. The reaction is 10(4)-fold faster than that observed with O(2) and is by far the most rapid iron-sulfur cluster nitrosylation reaction reported to date. An overall stoichiometry of [Fe(4)S(4)(Cys)(4)](2-) + 8NO → 2[Fe(I)(2)(NO)(4)(Cys)(2)](0) + S(2-) + 3S(0) has been established by determination of the sulfur products and their oxidation states. Kinetic analysis leads to a four-step mechanism that accounts for the observed NO dependence. DFT calculations suggest the possibility that the nitrosylation product is a novel cluster [Fe(I)(4)(NO)(8)(Cys)(4)](0) derived by dimerization of a pair of Roussin's red ester (RRE) complexes.     

Escherichia coli quinolinate synthetase does indeed harbor a [4Fe-4S] cluster

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, M?ssbauer, 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.     

Calculating standard reduction potentials of [4Fe–4S] proteins

The oxidation–reduction potentials of electron transfer proteins determine the driving forces for their electron transfer reactions. Although the type of redox site determines the intrinsic energy required to add or remove an electron, the electrostatic interaction energy between the redox site and its surrounding environment can greatly shift the redox potentials. Here, a method for calculating the reduction potential versus the standard hydrogen electrode, E°, of a metalloprotein using a combination of density functional theory and continuum electrostatics is presented. This work focuses on the methodology for the continuum electrostatics calculations, including various factors that may affect the accuracy. The calculations are demonstrated using crystal structures of six homologous HiPIPs, which give E° that are in excellent agreement with experimental results. © 2012 Wiley Periodicals, Inc.     

VFe3S4 single and double cubane clusters: synthesis, structures, and dependence of redox potentials and electron distribution on ligation and heterometal

Both vanadium and molybdenum cofactor clusters are found in nitrogenase. In biomimetic research, many fewer heterometal MFe3S4 cubane-type clusters have been synthesized with M = V than with M = Mo because of the well-established structural relationship of the latter to the molybdenum coordination unit in the enzyme. In this work, a series of single cubane and edge-bridged double cubane clusters containing the cores [VFe3(mu3-S)4]2+ and [V2Fe6(mu3-S)6(mu4-S)2]2+ have been prepared by ligand substitution of the phosphine clusters [(Tp)VFe3S4(PEt3)3]1+ and [(Tp)2V2Fe6S8(PEt3)4]. The single cubanes [(Tp)VFe3S4L3]2- and double cubanes [(Tp)2V2Fe6S8L4]4- (L= F-, N3-, CN-, PhS-) are shown by X-ray structures to have trigonal symmetry and centrosymmetry, respectively. Single cubanes form the three-member electron transfer series [(Tp)VFe3S4L3]3-,2-,1-. The ligand dependence of redox potentials and electron distribution in cluster cores as sensed by 57Fe isomer shifts (delta) have been determined. Comparison of these results with those previously determined for the analogous molybdenum clusters (Pesavento, Berlinguette, and Holm Inorg. Chem. 2007, 46, 510) allows detection of the influence of heterometal M on the properties. At constant M and variable L, redox potentials are lowest for pi-donor ligands and largest for cyanide and relate approximately with decreasing ferrous character in clusters with constant charge z = 2-. At constant L and z and variable M, EV > E(Mo) and delta(av)V < delta(av)Mo, demonstrating that M = Mo clusters are more readily oxidized and suggesting a qualitative relation between lower potentials (greater ease of oxidation) and ferrous character.     

Mechanism of glutaredoxin-ISU [2Fe-2S] cluster exchange

Exchange of [2Fe-2S] centers between Grx2 and the cluster scaffold protein ISU, and characterization of two mutually exclusive Grx2 binding sites on ISU by isothermal titration calorimetry supports a direct link for Grx and glutathione involvement in ISU promoted Fe-S cluster biosynthesis.     

Coordination and mechanism of reversible cleavage of S-adenosylmethionine by the [4Fe-4S] center in lysine 2,3-aminomutase

Lysine 2,3-aminomutase (LAM) catalyzes the interconversion of l-lysine and l-beta-lysine, by a radical mechanism initiated by the reversible, reductive homolytic scission of the C5'-S bond in S-adenosylmethionine (SAM) to form methionine and the 5'-deoxyadenosyl radical at the active site. LAM is a member of a superfamily of enzymes in which a [4Fe-4S]+ cluster with a unique, noncysteinyl coordinated Fe provides the electron required in the cleavage of SAM. Little is known of the mechanism by which the electron is inserted into SAM, and it is not known whether all enzymes of the family employ the same mechanism. Selenium X-ray absorption spectroscopy (XAS) in the reaction of Se-adenosyl-l-selenomethionine (SeSAM) in place of SAM shows that electron transfer occurs by an inner sphere mechanism culminating in direct ligation of selenomethionine to iron upon cleavage of SeSAM. Here, we report an electron nuclear double resonance (ENDOR) spectroscopic investigation of LAM to which has been bound 14N, 17O, 2H, or 13C labeled SAM. It is found that LAM exhibits the same motif for SAM binding to the [4Fe-4S]+,2+ clusters as does pyruvate formate lyase: chelation by the unique iron of the amino and carboxylato groups of SAM; close proximity of the methionine methyl group to the cluster. However, there appear to be significant, and possibly mechanistically important, differences in the details of the binding geometry of SAM. On the basis of the correlation of the ENDOR and XAS spectroscopic results, we postulate a mechanism by which LAM cleaves SAM to generate an intermediate where N, O, and S of the methionine product are bound to the octahedrally coordinated unique Fe of the [4Fe-4S] cluster.     

Carbon monoxide induced decomposition of the active site [Ni-4Fe-5S] cluster of CO dehydrogenase

During the past two years, crystal structures of Cu- and Mo-containing carbon monoxide dehydrogenases (CODHs) and Ni- and Fe-containing CODHs have been reported. The active site of CODHs from anaerobic bacteria (cluster C) is composed of Ni, Fe, and S for which crystallographic studies of the enzymes from Carboxydothermus hydrogenoformans, Rhodospirillum rubrum, and Moorella thermoaceticarevealed structural similarities in the overall protein fold but showed substantial differences in the essential Ni coordination environment. The [Ni-4Fe-5S] cluster C in the fully catalytically competent dithionite-reduced CODH II from C. hydrogenoformans (CODHII(Ch)) at 1.6 A resolution contains a characteristic mu(2)-sulfido ligand between Ni and Fe1, resulting in a square-planar ligand arrangement with four S-ligands at the Ni ion. In contrast, the [Ni-4Fe-4S] clusters C in CO-treated CODH from R. rubrum resolved at 2.8 A and in CO-treated acetyl-CoA synthase/CODH complex from M. thermoacetica at 2.2 and 1.9 A resolution, respectively, do not contain the mu(2)-sulfido ligand between Ni and Fe1 and display dissimilar geometries at the Ni ion. The [Ni-4Fe-4S] cluster is composed of a cubane [Ni-3Fe-4S] cluster linked to a mononuclear Fe site. The described coordination geometries of the Ni ion in the [Ni-4Fe-4S] cluster of R. rubrum and M. thermoacetica deviate from the square-planar ligand geometry in the [Ni-4Fe-5S] cluster C of CODHII(Ch). In addition, the latter was converted into a [Ni-4Fe-4S] cluster under specific conditions. The objective of this study was to elucidate the relationship between the structure of cluster C in CODHII(Ch) and the functionality of the protein. We have determined the CO oxidation activity of CODHII(Ch) under different conditions of crystallization, prepared crystals of the enzyme in the presence of dithiothreitol or dithionite as reducing agents under an atmosphere of N(2) or CO, and solved the corresponding structures at 1.1 to 1.6 A resolutions. Fully active CODHII(Ch) obtained after incubation of the enzyme with dithionite under N(2) revealed the [Ni-4Fe-5S] cluster. Short treatment of the enzyme with CO in the presence of dithiothreitol resulted in a catalytically competent CODHII(Ch) with a CO-reduced [Ni-4Fe-5S] cluster, but a prolonged treatment with CO caused the loss of CO-oxidizing activity and revealed a [Ni-4Fe-4S] cluster, which did not contain a mu(2)-S. These data suggest that the [Ni-4Fe-4S] cluster of CODHII(Ch) is an inactivated decomposition product originating from the [Ni-4Fe-5S] cluster.     

Electrochemical and theoretical study of the redox properties of transition metal complexes with [Pt2S2] cores

The oxidation processes undergone by the [Pt2(mu-S)2] core in [Pt2(P[intersection]P)2(mu-S)2](P[intersection]P = Ph2P(CH2)nPPh2, n= 2,3) complexes have been analysed on the basis of electrochemical measurements. The experimental results are indicative of two consecutive monoelectronic oxidations after which the [Pt2(mu-S)2] core evolves into [Pt2(mu-S2)]2+, containing a bridging disulfide ligand. However, the instability of the monoxidised [Pt2(P[intersection]P)2(mu-S)2]+ species formed initially, which converts into [Pt3(P[intersection]P)3(mu-S)2]2+, hampered the synthesis and characterisation of the mono and dioxidised species. These drawbacks have been surpassed by means of DFT calculations which have also allowed the elucidation of the structural features of the species obtained from the oxidation of [Pt2(P[intersection]P)2(mu-S)2] compounds. The calculated redox potentials corresponding to the oxidation processes are consistent with the experimental data obtained. In addition, calculations on the thermodynamics of possible processes following the degradation of [Pt2(P[intersection]P)2(mu-S)2]+ are fully consistent with the concomitant formation of monometallic [Pt(P[intersection]P)S2)] and trimetallic [Pt3(P[intersection]P)3(mu-S)2]2+ compounds. Extension of the theoretical study on the [Pt2Te2] core and comparisons with the results obtained for [Pt2S2] have given a more general picture of the behaviour of [Pt2X2](X = chalcogenide) cores subject to oxidation processes.     

The outer-sphere association of p-sulfonatothiacalix[4]arene with some Co(III) complexes: the effect on their redox activity in aqueous solutions

The effect of the ion-pairing of Co(III) complexes with p-sulfonatothiacalix[4]arene (STCA) on Fe(II)–Co(III) electron transfer rate was evaluated from the analysis and comparison of kinetic data in double Co(III)–Fe(II) and triple Co(III)–Fe(II)—STCA systems at various concentration conditions. Complexes [Co(en)₃]³⁺(1), [Co(en)₂ox]⁺(2), [Co(dipy)₃]³⁺ (3), [Co(His)₂]⁺(4) and [Fe(CN)₆]⁴⁻ were chosen as Co(III) and Fe(II) compounds. The effect of STCA was found to correlate with the association mode. The outer-sphere association with STCA was found to exhibit the insignificant effect on Fe(II)–Co(III) electron transfer k _et constants for complexes 3 and 4 with bulky and rigid chelate rings, while more sufficient inclusion of flexible ethylendiaminate rings of 1 and 2 into the cavity of STCA results in the unusual increase of k _et.