Terminal Thiolate Ligands Research Articles

Di- and tri-nuclear ruthenium nitrosyl complexes containing thiolate ligands

Treatment of Ru(NO)Cl3 with NaSC6F4H (C6F4HSH = 2,3,5,6-tetrafluorothiophenol) afforded the hydroxo-bridged dimer Na(H2O)2[Ru(NO)(SC6HF4)2]2(μ-SC6HF4)2(μ-OH) (Na(H2O)21), in which the {Na(H2O)2}+ moiety binds to the diruthenium core via the μ-hydroxo ligand and three ortho fluorine atoms of the thiolate ligands. Metathesis of Na(H2O)21 with Bun4NBr and Ph4PCl afforded Na-free (Bun4N)[1] and (Ph4P)[1], respectively. Treatment of Ru(NO)Cl3 with NaSBut afforded the trinuclear oxo-sulfido cluster Na(H2O)2[Ru(NO)(SBut)(μ-SBut)]3(μ3-S)(μ3-O) (Na(H2O)22) that contains a trinuclear {Ru3(SBut)3} core capped by a μ3-oxo and a μ3-sulfido ligand. The {Na(H2O)2}+ moiety binds to the triruthenium core via the μ3-oxo and two terminal thiolate ligands. Metathesis of Na(H2O)22 with Bun4NBr gave (Bun4N)[2]. Treatment of Ru(NO)Cl3 with NaStipp (tipp = 2,4,6-triisopropylphenyl) gave mononuclear Ru(NO)(Stipp)3(tippSH) (3). The crystal structures of Na(H2O)21, (Ph4P)[1], and Na(H2O)22 have been determined.

Effect of H2 binding on the nonadiabatic transition probability between singlet and triplet states of the [NiFe]-hydrogenase active site.

We investigate the effect of H2 binding on the spin-forbidden nonadiabatic transition probability between the lowest energy singlet and triplet electronic states of [NiFe]-hydrogenase active site model, using a velocity averaged Landau-Zener theory. Density functional and multireference perturbation theories were used to provide parameters for the Landau-Zener calculations. It was found that variation of the torsion angle between the terminal thiolate ligands around the Ni center induces an intersystem crossing between the lowest energy singlet and triplet electronic states in the bare active site and in the active site with bound H2. Potential energy curves between the singlet and triplet minima along the torsion angle and H2 binding energies to the two spin states were calculated. Upon H2 binding to the active site, there is a decrease in the torsion angle at the minimum energy crossing point between the singlet and triplet states. The probability of nonadiabatic transitions at temperatures between 270 and 370 K ranges from 35% to 32% for the active site with bound H2 and from 42% to 38% for the bare active site, thus indicating the importance of spin-forbidden nonadiabatic pathways for H2 binding on the [NiFe]-hydrogenase active site.

Protein induced singlet–triplet quasidegeneracy in the active site of [NiFe]-hydrogenase

Molecular hydrogen oxidation and reduction on [NiFe]-hydrogenase is an inspiring example of using abundant first row transition metals to catalyze biologically and industrially important chemical reactions. We demonstrate that by rotating terminal thiolate ligands in the active site of [NiFe]-hydrogenase, either the singlet or triplet electronic state can be made a ground state. The two states become degenerate when the ligand orientations are similar to those observed in [NiFe]-hydrogenase, where this orientation is enforced by the protein backbone. The unusual distorted coordination geometry of Ni can explain the inability of the structural models of [NiFe]-hydrogenase to bind molecular hydrogen.

Interaction of Metallothionein-2 with Platinum-Modified 5′-Guanosine Monophosphate and DNA

Human metallothioneins (MTs), a family of cysteine- and metal-rich metalloproteins, play an important role in the acquired resistance to platinum drugs. MTs occur in the cytosol and the nucleus of the cells and sequester platinum drugs through interaction with their zinc-thiolate clusters. Herein, we investigate the ability of human Zn 7MT-2 to form DNA-Pt-MT cross-links using the cisplatin- and transplatin-modified plasmid DNA pSP73. Immunochemical analysis of MT-2 showed that the monofunctional platinum-DNA adducts formed DNA- cis/ trans-Pt-MT cross-links and that platinated MT-2 was released from the DNA- trans-Pt-MT cross-links with time. The DNA- cis/ trans-Pt-MT cross-links were also formed in the presence of 2 mM glutathione, a strong S-donor ligand. Independently, we used 5'-guanosine monophosphate (5'-GMP) platinated at the N7 position as a model of monofunctional platinum-DNA adducts. Comparison of reaction kinetics revealed that the formation of ternary complexes between Zn 7MT-2 and cis-Pt-GMP was faster than that of the trans isomer. The analysis of the reaction products with time showed that while the formation of ternary GMP- trans-Pt-MT complex(es) is accompanied by 5'-GMP release, a stable ternary GMP- cis-Pt-MT complex is formed. In the latter complex, a fast initial formation of two Pt-S bonds was followed by a slow formation of an additional Pt-S bond yielding an unusual Pt(II)S 3N coordination with N7-GMP as the only N-donor ligand. The ejection of negligible zinc from the zinc-thiolate clusters implies the initial formation of Zn-(mu-SCys)-Pt bridges involving the terminal thiolate ligands. The biological implications of these studies are discussed.

Synthesis and Study of Hexanuclear Molybdenum Clusters Containing Thiolate Ligands

Four hexanuclear molybdenum chloride cluster complexes containing terminal thiolate ligands have been synthesized and fully characterized. (Bu 4N) 2[Mo 6Cl 8(SEt) 6] was prepared by reacting Na 2[Mo 6Cl 8(OMe) 6] with an excess of ethanethiol in refluxing tetrahydrofuran. (PPN) 2[Mo 6Cl 8(SBu) 6], (Bu 4N) 2[Mo 6Cl 8(SBn) 6], and (Bu 4N) 2[Mo 6Cl 8(SNC 8H 6) 6] (C 8H 6NS (-) = 3-indolylthiolate) were subsequently prepared in the reaction of [Mo 6Cl 8(SEt) 6] (2-) with an excess of HSR (R = Bu, Bn or 3-indolyl). Single crystal X-ray diffraction analyses were performed on two of these complexes: (PPN) 2[Mo 6Cl 8(SEt) 6].Et 2O, crystallizes in the triclinic space group P1 with a = 12.3894(11), b = 13.7651(12), c = 15.0974(13), alpha = 103.975(2), beta = 99.690(2), gamma = 98.062(2), and Z = 1; (PPh 3Me) 2[Mo 6Cl 8(SBn) 6].2NO 2CH 3, also crystallizes in the P1 space group with a = 12.1574(16), b = 13.4441(17), c = 14.2132(18), alpha = 89.654(2), beta = 88.365(2), gamma = 71.179(2), and Z = 1. Our studies demonstrate that [Mo 6Cl 8(SEt) 6] (2-) displays luminescent properties and that the same complex undergoes substitution reactions with different thiols, as well as reaction with electrophilic reagents such as MeI.

Mechanism of the Reactions of Synthetic Fe−S-Based Clusters with PhCOCl: Parallel Pathways Involving Free and Coordinated Thiolate as Nucleophiles

Terminal thiolate ligands on the synthetic Fe-S-based clusters [Fe4S4(SR)4]2- (R = Et or SPh) or [{MoFe3S4(SPh)3}2(mu-SPh)3]3- are replaced by chloride in a reaction with PhCOCl to produce [Fe4S4Cl4]2- and [{MoFe3S4Cl3}2(mu-SPh)3]3-, respectively. Kinetic studies using stopped-flow spectrophotometry show that, in general, the mechanisms of these reactions in MeCN occur by two pathways. One pathway is independent of the concentration of PhCOCl and involves rate-limiting dissociation of the thiolate ligand. The free thiolate subsequently reacts with PhCOCl to produce PhCOSR and the Cl- which binds to the vacant site on the cluster. The second pathway exhibits a nonlinear dependence on the concentration of PhCOCl and involves initial, rapid binding of PhCOCl to the cluster followed by intramolecular thiolate ligand attack on the coordinated acid chloride. The intermediate in which PhCOCl is bound to the cluster has been detected spectrophotometrically. The ways in which the rates of the reactions between PhCOCl and Fe-S-based clusters are affected by changes of the terminal thiolate, the metal composition of the cluster core, and the protonation state of the cluster have been investigated and are compared with the effect these same changes have on the rates of nucleophilic substitution.

A Monomeric, Base‐Free Samarium(II) Thiophenolate with a π‐Encapsulated Rare‐Earth Metal

AbstractThe deep purple, alkane‐soluble complex Sm(SAr*)2 (1) (Ar* = 2,6‐Trip2C6H3; Trip = 2,4,6‐iPr3C6H2) has been prepared by salt metathesis reaction of SmI2 with KSAr*. The solid‐state structure shows monomeric units with the metal atom bonded to sulfur atoms of two terminal thiolate ligands (av. Sm–S: 281.6 pm). Additional η6‐π‐arene interactions are observed to two C6H2 rings of the flanking Trip substituents (av. Sm···C: 307.1 pm).

Organization and Assembly of Metal-Thiolate Clusters in Epithelium-specific Metallothionein-4

Mammalian metallothionein-4 (MT-4) was found to be specifically expressed in stratified squamous epithelia where it plays an essential but poorly defined role in regulating zinc or copper metabolism. Here we report on the organization, stability, and the pathway of metal-thiolate cluster assembly in MT-4 reconstituted with Cd(2+) and Co(2+) ions. Both the (113)Cd NMR studies of (113)Cd(7)MT-4 and the spectroscopic characterization of Co(7)MT-4 showed that, similar to the classical MT-1 and MT-2 proteins, metal ions are organized in two independent Cd(4)Cys(11) and Cd(3)Cys(9) clusters with each metal ion tetrahedrally coordinated by terminal and bridging cysteine ligands. Moreover, we have demonstrated that the cluster formation in Cd(7)MT-4 is cooperative and sequential, with the Cd(4)Cys(11) cluster being formed first, and that a distinct single-metal nucleation intermediate Cd(1)MT-4 is required in the cluster formation process. Conversely, the absorption and circular dichroism features of metal-thiolate clusters in Cd(7)MT-4 indicate that marked differences in the cluster geometry exist when compared with those in Cd(7)MT-1/2. The biological implication of our studies as to the role of MT-4 in zinc metabolism of stratified epithelia is discussed.

Metal‐Binding Properties of the Peptide APP170–188: A Model of the ZnII‐Binding Site of Amyloid Precursor Protein (APP)

Amyloid precursor protein (APP) plays a key role in Alzheimer's disease (AD), although the function of this membrane protein is still unclear. Metal ions are implicated in AD and they also interact with APP. APP possesses a strong ZnII binding site, which is evolutionary conserved. In this paper a synthetic peptide, APP170-188, with a sequence corresponding to the conserved ZnII-binding domain of APP, was synthesised and its metal-binding properties analysed. Titration experiments pointed to the binding of a stoichiometric amount of divalent ions. Further studies indicated that the binding of divalent metals like ZnII, CdII and CoII induces the dimerisation of the peptide. This dimer contains a dinuclear cluster in which the two divalent metals are bridged by two thiolate ligands from cysteine residues. The other two ligands of the tetrahedral coordination sites of each metal ion are terminal thiolate ligands. This structure was supported by the following arguments. The complex formed with CoII presents the characteristic features for tetrahedral tetrathiolate coordination in its UV-visible spectrum. The sequence of APP170-188 contains only three cysteine residues, which is incompatible with a monomeric CoII-APP170-188 complex. EPR measurements of the complex with one equivalent of CoII show almost no signal at 4 K, which is compatible with an antiferromagnetic spin-coupling of the metal ions in a cluster structure. Size-exclusion chromatography indicated that the elution time for the complexes with ZnII and CdII corresponds to the expected molecular weight of a dimer. The circular dichroism (CD) spectrum of the complex with one equivalent of CdII shows a band at 265 nm+, and an ellipticity similar to those observed for similar CdII-thiolate clusters. Possible biological implications of the ZnII binding site and the metal-induced dimerisation are discussed.

Application of a universal force field to mixed Fe/Mo-S/Se cubane and heterocubane clusters. 2. Substitution of iron by molybdenum in Fe4(S/Se)4 clusters with terminal halide and thiolate ligands.

Infrared and Raman spectra of Fe(4)(S/Se)(4) clusters with terminal halide ligands and MoFe(3)S(4) clusters with terminal thiolate and halide ligands are presented and interpreted on the basis of the force fields determined in the accompanying paper. The Raman spectra of halide coordinated Fe(4)(S/Se)(4) clusters are characterized by the fact that vibrations of the terminal ligands appear with little or vanishing intensity. Infrared and Raman spectra of MoFe(3)S(4) clusters with terminal thiolates are correlated to those of corresponding Fe(4)S(4) systems, which were investigated in part 1 of this study and interpreted with normal coordinate analysis. Band assignments are checked by employing MoFeS(4) clusters with terminal halide ligands. Spectra of these systems are in turn compared to those of their Fe(4)S(4) counterparts, i.e., Fe-S cubane clusters with chloro, bromo, and iodo ligands. A consistent interpretation of all spectra is presented. General implications of these results are discussed.

σ-Donor versus η6-π-Arene Interactions in Monomeric Europium(II) and Ytterbium(II) Thiolates − An Experimental and Computational Study

The base-free, hydrocarbon-soluble complexes M(SAr*)2 (4a: M = Eu, orange; 4b: M = Yb, purple; Ar* = 2,6-Trip2C6H3; Trip = 2,4,6-iPr3C6H2) have been prepared by a protolysis reaction of the Grignard-analogous compound RLnI (R = 2-F3CC6H4) with HSAr*. Compound 4b has been characterized by melting point, elemental analysis, 1H, 13C, and 171Yb NMR, IR spectroscopy, UV/Vis spectrophotometry, mass spectrometry, and X-ray crystallography. Additionally, the purple YbIII complex YbI2(SAr*)(THF)3 (3) and the yellow DME adduct Yb(SAr*)2(dme)2 (5) have been synthesized and characterized by X-ray crystallography. The solid-state structures of 4a and 4b (as THF or benzene hemisolvates) show monomeric units with the metal atom bonded to two terminal thiolate ligands [av. M−S: 281.7 pm (4a)/269.1 pm (4b)]. Additional η6-π-arene interactions are observed to two C6H2 rings of the Trip substituents [av. M···C: 306.5 pm (4a)/297.3 pm (4b)]. The binding energy for these interactions has been determined by variable-temperature 1H NMR spectroscopy to be 54.3 kJ mol−1 (in methylcyclohexane) and 57.1 kJ mol−1 (in toluene). The nature and strength of the η6-π-arene bonding has been studied by ab initio calculations on the model systems [M(arene)]2+ (arene = C6H6, C6F6, 1,3,5-Me3C6H3, 1,3,5-iPr3C6H3) and Yb(SH)2(C6H6)n (n = 1, 2). The results are compared with the binding energies in the σ-donor adducts [M(THF)]2+, [M(dme)]2+, and [M(imidazol-2-ylidene)]2+.

S K-edge X-ray absorption studies of tetranuclear iron-sulfur clusters: mu-sulfide bonding and its contribution to electron delocalization.

X-ray absorption spectroscopy (XAS) at the sulfur ( approximately 2470 eV) and chlorine ( approximately 2822 eV) K-edges has been applied to a series of 4Fe-4S model complexes. These are compared to 2Fe-2S model complexes to obtain insight into the localized ground state in the mixed-valence dimer versus the delocalized ground state in the mixed-valence tetramer. The preedges of hypothetical delocalized mixed-valence dimers [Fe(2)S(2)](+) are estimated using trends from experimental data and density functional calculations, for comparison to the delocalized mixed-valence tetramer [Fe(4)S(4)](2+). The differences between these two mixed-valence sites are due to the change of the sulfide-bridging mode from micro(2) to micro(3). The terminal chloride and thiolate ligands are used as spectator ligands for the electron density of the iron center. From the intensity of the preedge, the covalency of the terminal ligands is found to increase in the tetramer as compared to the dimer. This is associated with a higher effective nuclear charge on the iron in the tetramer (derived from the energies of the preedge). The micro(3)-bridging sulfide in the tetramer has a reduced covalency per bond (39%) as compared to the micro(2)-bridging sulfide in the dimer (51%). A simple perturbation model is used to derive a quadratic dependence of the superexchange coupling constant J on the covalency of the metal ions with the bridging ligands. This relationship is used to estimate the superexchange contribution in the tetramer (J = -156 cm(-)(1)) as compared to the mixed-valence dimer (J = -360 cm(-)(1)). These results, combined with estimates for the double exchange and the vibronic coupling contributions of the dimer sub-site of the tetramer, lead to a delocalized S(t) = (9)/(2) spin ground state for the mixed-valence dimer in the tetramer. Thus, the decrease in the covalency, hence the superexchange pathway associated with changing the bridging mode of the sulfides from micro(2) to micro(3) on going from the dimer to the tetramer, significantly contributes to the delocalization of the excess electron over the dimer sub-site in the tetramer.

Reactivity of Cobalt(III) Amine-Thiolate Complexes with Terminal and Bridging Thiolate Functions towards Hydrogen Peroxide

The reactivity of CoIII amine-thiolate complexes with terminal and bridging thiolate functions towards oxidizing agents has been investigated. The mononuclear CoIII N3S3 complex [CoIII(L1)] (2) (H3L1 represents the hexadentate ligand N,N′,N″-Tris(2-thio-benzyl)-1,1,1 -tris- (aminomethyl)ethane) featuring three terminal thiolate ligands, and the binuclear N3CoIII- (μ-S)3CoIIIN3 complex [CoIII 2(L2)]3+ (4) (H3L2 = N,N′,N″-Tris-[2-thio-3-aminomethyl-5-terrbutyl- benzyl]-1,1,1-tris(aminomethyl)ethane) featuring three bridging thiolates were selected. Hydrogen peroxide was the oxidizing agent. Whereas the thiolato-bridged complex 4 is resistant towards oxidation by hydrogen peroxide, 2 undergoes a ligand-based oxidation reaction to give the amine-sulfinate complex [Co(L1′)] 5, where all three terminal thiolates have been oxidized to sulfinates without gross structural changes of the parent complex 2. In contrast to 4, the cyclic voltammogram of 2 reveals an irreversible oxidation wave at E = +0.52 V vs SCE which can be attributed to a ligand-centered oxidation reaction. 4 and 5 have been structurally characterized by X-ray crystallography.

Synthesis, emission, and electrochemical properties of luminescent dinuclear zinc(II) chalcogenolate complexes. Dynamic 1H NMR studies and X-ray crystal structure of [(bpy)Zn2(SC6H4-Cl-p)(mu-SC6H4-Cl-p)(mu-OAc)2

A series of novel luminescent dinuclear zinc(II) diimine complexes with bridging chalcogenolate ligands have been synthesized, in which the two zinc atoms were found to exist in different coordination environment. The luminescence and electrochemical behavior of these complexes have been studied. These complexes have also been shown to exhibit dynamic fluxional behavior in solution due to an exchange of the bridging and terminal thiolate ligands. The mechanism and kinetics of which have been investigated by variable-temperature 1H NMR studies. The X-ray crystal structure of [(bpy)Zn2(SC6H4-Cl-p)(mu-SC6H4-Cl-p)(mu-OAc)2] has also been determined.

Protonation and Alkylation of a Dinuclear Nickel Thiolate Complex.

Reaction of a dinuclear Ni thiolate complex featuring both terminal and bridging thiolate ligands with 1 equiv of an alkylating agent leads to the production of a dinuclear complex where one of the terminal thiolate ligands has reacted to form a thioether ligand. The product of one such reaction has been crystallographically characterized. This structure reveals that little change in the core structure of the complex occurs upon alkylation. Similarly, reaction of the dinuclear Ni complex with 1 equiv of H+ leads to the isolation of a dinuclear complex containing a thiol ligand. The structure of this complex is deduced from NMR and XAS spectroscopy. Again, little change in structure can be detected. Nonetheless, the redox properties of the complex are dramatically affected. Thus protonation provides one possible mechanism for modulating the redox potential of metalloenzymes containing Ni thiolate active sites without affecting the structure of the Ni site.

The association of metallothionein with phosphate

Dose-dependent binding of inorganic phosphate to pre-irradiated metallothionein (MT) was observed by gel-filtration using sodium [ 32P]phosphate, whereas no association of phosphate with the natural MT can be observed. The circular dichroism (CD) spectra indicate that after irradiation, some terminal thiolate ligands in MT are transformed to bridging ones, and some destroyed, which results in unsaturated coordination of metal ions. Accordingly, it is reasonable to assume that in irradiated MT, nonsulfur liganss, e.g. oxygen in Pi, take part in metal coordinations, which leads to the interactions of MT with Pi.

Sequential proton resonance assignments and metal cluster topology of lobster metallothionein-1.

NMR studies of 111Cd6-MT 1 from lobster have been conducted to determine coordination structure of Cd-thiolate binding in the protein. Sequential proton resonance assignments were made using standard two-dimensional 1H NMR methods. Two-dimensional 1H-111Cd HMQC experiments were then carried out to determine the cadmium-cysteine connectivities in the protein. With this information, it was established that the six Cd ions exist in two different Cd3S9 clusters, each involving three bridging and six terminal thiolate ligands. Sequential cysteines in the sequence provide the sulfhydryl ligands for each cluster and do not overlap, as has been found in mammalian metallothionein. Comparison of the N-terminal, Cd3S9 B-type cluster of lobster MT 1 with the Cd3S9 cluster from rabbit MT 2 shows that while eight of the nine cysteine residues occupy homologous positions in their sequences, three of the 12 Cd-thiolate connectivities are different. Similarly, the C-terminal B-cluster of lobster MT 1 was compared with the Cd4S11 cluster of mammalian MT 2, excluding the two terminal cysteine sulfhydryl groups that convert this cluster from A- to B-type. As above, eight of nine cysteine positions are identical, yet five of 12 Cd-sulfhydryl connections are different. These differences are expanded when the role of each cysteine as bridging or terminal ligands in the clusters is considered.

Reactions of unsaturated nickel-tungsten and nickel-molybdenum complexes with organic disulfides. Synthetic and structural studies

The behavior of the unsaturated complex ([eta]-C[sub 5]Me[sub 5])Ni-W(CO)[sub 3]([eta]-C[sub 5]H[sub 4]Me) (Ni-W, 1) toward selected chalcogenide-containing ligands is described. The Ni-W species is inert to Me[sub 2]S under ambient reaction conditions, but disulfides and diselenides react with 1. Diphenyl disulfide, dimethyl disulfide, and diphenyl diselenide oxidatively add across the mixed-metal bond to afford ([eta]-C[sub 5]Me[sub 5])Ni([mu]-CO)([mu]-ER)W(CO)(ER)([eta]-C[sub 5]H[sub 4]Me) (Ni-W; Er = SPh, SMe, SePh), which contain bridging and terminal thiolate or selenate ligands. A similar Ni-Mo product was formed when ([eta]-C[sub 5]Me[sub 5])Ni-Mo(CO)[sub 3]([eta]-C[sub 5]H[sub 4]Me) was treated with PhS[sub 2]Ph. In most cases the reactions are clean, but [([eta]-C[sub 5]Me[sub 5])Ni([mu]-SePh)][sub 2] was also isolated in the diphenyl diselenide reaction. All the complexes are fluxional on the NMR time scale. The bis(benzenethiolate) nickel-tungsten species was studied by VT [sup 1]H NMR: some dynamic behavior was arrested at [minus]80[degrees]C. Structures of ([eta]-C[sub 5]Me[sub 5])Ni([mu]-CO)([mu]-CO)([mu]-SPh)W(CO)(SPh)([eta]-C[sub 5]H[sub 4]Me) (Ni-W, 2a) and [([eta]-C[sub 5]Me[sub 5])Ni([mu]-SePh)][sub 2] (3) were ascertained by single-crystal X-ray diffraction studies. 26 refs., 4 figs., 6 tabs.

Synthesis and structure of [NEt 4]Fe(CO) 3(μ-SPh) 2Mo(CO) 3(SPh): A heterodinuclear compound with bridging and terminal thiolate ligands

A new heterodinuclear compound, [NEt 4]Fe(CO) 3(μ-SPh) 2Mo(CO) 3(SPh), has been prepared from the reaction of Fe(CO) 4Br 2 with [NEt 4]SPh and molybdenum carbonyl starting materials. The compound has been characterized spectroscopically and by X-ray diffraction.

Hg7(SC6H11)12Br2], A novel mercury cage molecule with bridging and terminal thiolate ligands and with terminal and µ6bromide

Reaction of HgBr2 with sodium cyclohexanethiolate in methanol, followed by recrystallisation from pyridine, gives the discrete molecular complex [Hg7(SC6H11)12Br2], in which six Hg atoms form a distroted octahedron around a central Br, thiolate ligands are bridging or terminal, and a HgBr unit with terminal Br caps three thiolates on one side of the molecule.