Redox chemistry and electronic properties of 2,3,5,6-tetrakis(2-pyridyl)pyrazine-bridged diruthenium complexes controlled by N,C,N '-biscyclometalated ligands

To investigate the consequences of cyclometalation for electronic communication in dinuclear ruthenium complexes, a series of 2,3,5,6-tetrakis(2-pyridyl)pyrazine (tppz) bridged diruthenium complexes was prepared and studied. These complexes have a central tppz ligand bridging via nitrogen-to-ruthenium coordination bonds, while each ruthenium atom also binds either a monoanionic, N,C,N'-terdentate 2,6-bis(2'-pyridyl)phenyl (R-N boolean AND C boolean AND N) ligand or a 2,2':6',2 ''-terpyridine (tpy) ligand. The N,C,N'-, that is, biscyclometalation, instead of the latter N,N', N ''-bonding motif significantly changes the electronic properties of the resulting complexes. Starting from well-known [{Ru(tpy)}(2)(mu-tppz)](4+) (tpy = 2,2':2 '',6-terpyridine) ([3](4+)) as a model compound, the complexes [{Ru(R-N boolean AND C boolean AND N)}(mu-tppz){Ru(tpy)}](3+) (R-N boolean AND C(H)boolean AND N = 4-R-1,3-dipyridylbenzene, R = H ([4a](3+)), CO2Me ([4b](3+))), and [{Ru(R-N boolean AND C boolean AND N)}(2)(mu-tppz)](2+), (R = H ([5a](2+)), CO2Me ([5b](2+))) were prepared with one or two N,C,N'-cyclometalated terminal ligands. The oxidation and reduction potentials of cyclometalated [4](3+) and [5](2+) are shifted negatively compared to non-cyclometalated [3](4+), the oxidation processes being affected more significantly. Compared to [3](4+), the electronic spectra of [5](2+) display large bathochromic shifts of the main MLCT transitions in the visible spectral region with low-energy absorptions tailing down to the NIR region. One-electron oxidation of [3](4+) and [5](2+) gives rise to low-energy absorption bands. The comproportionation constants and NIR band shape correspond to delocalized Robin-Day class III compounds. Complexes [4a](3+) (R = H) and [4b](3+) (R = CO2Me) also exhibit strong electronic communication, and notwithstanding the large redox-asymmetry the visible metal-to-ligand charge-transfer absorption is assigned to originate from both metal centers. The potential of the first, ruthenium-based, reversible oxidation process is strongly negatively shifted. On the contrary, the second oxidation is irreversible and cyclometalated ligand-based. Upon one-electron oxidation, a weak and low-energy absorption arises.

A phosphorus analogue of Bis(eta(4)-cyclobutadiene)iron(0)

P makes it possible: The convenient oxidative synthesis of the 16-electron organophosphorus iron sandwich complex [Fe(4-P2C2tBu2)2] suggests that the elusive all-carbon complex [Fe(4-C4H4)2] is a viable synthetic target.

Locally twisted cubes are 4-pancyclic

The locally twisted cube is a newly introduced interconnection network for parallel computing. Ring embedding is an important issue for evaluating the performance of an interconnection network. In this paper, we investigate the problem of embedding rings into a locally twisted cube. Our main contribution is to find that, for each integer l is an element of (4,5,...,2(n)}, a ring of length I can be embedded into an n-dimensional locally twisted cube so that both the dilation and the load factor are one. As a result, a locally twisted cube is Hamiltonian. We conclude that a locally twisted cube is superior to a hypercube in terms of ring embedding capability. (C) 2004 Elsevier Ltd. All rights reserved.

Heterosite effects in novel heteronuclear clusters [OS2Ru(CO)(11)(PPh3)] and Os2Ru(CO)(10)(2-acetylpyridine-N-isopropylimine)]

A new synthetic route towards the mixed-metal cluster [OS2Ru(CO)(12)] is described together with the syntheses of its PPh3 and iPr-AcPy (iPr-AcPy = 2-acetylpyridine-N-isopropylimine) derivatives. The molecular structures of the novel clusters [Os2Ru(CO)(11)(PPh3)] and [Os2Ru(CO)(10)(iPr-AcPy)] were determined on the basis of crystalline solid solutions of the Os2Ru and corresponding Os-3 species. The structures reveal that coordination of the Lewis bases occurs exclusively at the ruthenium site of [Os2Ru(CO)(12)], which is in agreement with density functional theory (DFT) calculations on several structural isomers of these compounds. According to the time-dependent DFT results, the lowest optically accessible excited state of [Os2Ru(CO)(10)(iPr-AcPy)] has a prevailing sigma(Ru-Os-2)pi*(iPr-AcPy) character, with a partial sigma sigma*(Ru-Os-2) contribution. In weakly coordinating 2-chlorobutane, the excited state has a lifetime tau = 10.4 +/- 1.2 ps and produces biradicals considerably faster than observed for [Os-3(CO)10(iPr-AcPy) (tau = 25.3 +/- 0.7ps)]. In coordinating acetonitrile, the excited state of [Os2Ru(CO)(10)(iPr-AcPy)] decays mono-exponentially with a lifetime tau = 2.1 +/- 0.2 ps. In contrast to [Os-3(CO)(10)(iPr-AcPy)] that forms biradicals as the main primary photoproduct even in strongly coordinating solvents, zwitterion formation from the solvated lowest excited state is observed for the heterometallic cluster. This is concluded from time-resolved absorption studies in the microsecond time domain. Due to the lower tendency of the coordinatively unsaturated Ru+(CO)(2)(iPr-AcPy-/0) moiety to bind a Lewis base, the heteronuclear biradical and zwitterionic photoproducts live significantly shorter than their triosmium counterparts. The influence of the weaker Os-2-Ru(iPr-AcPy) bond on the redox reactivity is clearly reflected in very reactive radical anions formed upon electrochemical reduction of [Os2Ru(CO)(10)(iPr-AcPy)]. The dimer [-OS(CO)(4)-Os(CO)(4)-Ru(CO)(2)(iPr-AcPy)](2)(2-) is the only IR-detectable intermediate reduction product. The dinuclear complex [Os-2(CO)(8)](2-) and insoluble [Ru(CO)(2)(iPr-AcPy)](n), are the ultimate reduction products, proving fragmentation of the OS2Ru core.

Strongly nucleophilic RhI centre in square-planar complexes with terdentate (κ3) 2,2′:6′,2′′-terpyridine ligands: crystallographic, electrochemical and density functional theoretical studies

Rh-I-terpyridine complexes have been unambiguously formed for the first time. The 2,21:6',2"-terpyridine (tpy), 4'-chloro-2,2':6',2"-terpyridine (4'-Cl-tpy) and 4'-(tert-butyldimethylsilyl-ortho-carboranyl)-2,2':6',2"-terpyridine (carboranyl-tpy) ligands were used for successful syntheses and characterisation of the corresponding Rh-I complexes with halide coligands, [Rh(X)(4'-Y-terpyridine)] (X = Cl, Y = H, Cl, carboranyl; X = Br, Y = H). All four neutral Rh-tpy complexes are square planar, with Rh-X bonds in the plane of the 4'-Y-terpyridine ligands. Full characterisation of these dark blue, highly air-sensitive compounds was hampered by their poor solubility in various organic solvents. This is mainly due to the formation of pi-stacked aggregates, as evidenced by the crystal structure of [Rh(Cl)(tpy)]; in addition, [Rh(Cl)(carboranyl-tpy)] merely forms discrete dimers. The (bonding) properties of the novel Rh-I-terpyridine complexes have been studied with single-crystal X-ray diffraction, (time-dependent) density functional theoretical (DFT) calculations, far-infrared spectroscopy, electronic absorption spectroscopy and cyclic voltammetry. From DFT calculations, the HOMO of the studied Rh-I-terpyridine complexes involves predominantly the metal centre, while the LUMO resides on the terpyridine ligand. Absorption bands of the studied complexes in the visible region (400-900 nm) can be assigned to MLCT and MLCT/XLCT transitions. The relatively low oxidation potentials of [Rh(X)(tpy)] (X = Cl, Br) point to a high electron density on the metal centre. This makes the Rh-I-terpyridine complexes strongly nucleophilic and (potentially) highly reactive towards various (small) substrate molecules containing carbon-halide bonds.

Self-assembled molecular complexes and coordination polymers of CdII, hexamine, and monocarboxylates: structural analysis and theoretical studies of supramolecular interactions

Four new cadmium(II) complexes [Cd-2(bz)(4)(H2O)(4)(mu 2-hmt)]center dot Hbz center dot H2O (1), [Cd-3(bz)(6)(H2O)(6)(mu 2-hmt)(2)]center dot 6H(2)O (2), [Cd(pa)(2)(H2O)(mu(2)-hmt)](n) (3), and {[Cd-3(ac)(6)(H2O)(3)(mu(3)-hmt)(2)]center dot 6H(2)O}(n) (4) with hexamine (hmt) and monocarboxylate ions, benzoate (bz), phenylacetate (pa), or acetate (ac) have been synthesized and characterized structurally. Structure determinations reveal that 1 is dinuclear, 2 is trinuclear, 3 is a one-dimensional (1D) infinite chain, and 4 is a two-dimensional (2D) polymer with fused hexagonal rings consisting of Cd-II and hmt. All the Cd-II atoms in the four complexes (except one CdII in 2) possess seven-coordinate pentagonal bipyramidal geometry with the various chelating bidentate carboxylate groups in equatorial sites. One of the CdII ions in 2, a complex that contains two monodentate carboxylates is in a distorted octahedral environment. The bridging mode of hmt is mu 2- in complexes 1-3 but is mu 3- in complex 4. In all complexes, there are significant numbers of H-bonds, C-H/pi, and pi-pi interactions which play crucial roles in forming the supramolecular networks. The importance of the noncovalent interactions in terms of energies and geometries has been analyzed using high level ab initio calculations. The effect of the cadmium coordinated to hmt on the energetic features of the C-H/pi interaction is analyzed. Finally, the interplay between C-H/pi and pi-pi interactions observed in the crystal structure of 3 is also studied.

4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1

TRPA1 is an excitatory ion channel expressed by a subpopulation of primary afferent somatosensory neurons that contain substance P and calcitonin gene-related peptide. Environmental irritants such as mustard oil, allicin, and acrolein activate TRPA1, causing acute pain, neuropeptide release, and neurogenic inflammation. Genetic studies indicate that TRPA1 is also activated downstream of one or more proalgesic agents that stimulate phospholipase C signaling pathways, thereby implicating this channel in peripheral mechanisms controlling pain hypersensitivity. However, it is not known whether tissue injury also produces endogenous proalgesic factors that activate TRPA1 directly to augment inflammatory pain. Here, we report that recombinant or native TRPA1 channels are activated by 4-hydroxy-2-nonenal (HNE), an endogenous alpha,beta-unsaturated aldehyde that is produced when reactive oxygen species peroxidate membrane phospholipids in response to tissue injury, inflammation, and oxidative stress. HNE provokes release of substance P and calcitonin gene-related peptide from central (spinal cord) and peripheral (esophagus) nerve endings, resulting in neurogenic plasma protein extravasation in peripheral tissues. Moreover, injection of HNE into the rodent hind paw elicits pain-related behaviors that are inhibited by TRPA1 antagonists and absent in animals lacking functional TRPA1 channels. These findings demonstrate that HNE activates TRPA1 on nociceptive neurons to promote acute pain, neuropeptide release, and neurogenic inflammation. Our results also provide a mechanism-based rationale for developing novel analgesic or anti-inflammatory agents that target HNE production or TRPA1 activation.

Trypsin IV or mesotrypsin and p23 cleave protease-activated receptors 1 and 2 to induce inflammation and hyperalgesia

Although principally produced by the pancreas to degrade dietary proteins in the intestine, trypsins are also expressed in the nervous system and in epithelial tissues, where they have diverse actions that could be mediated by protease-activated receptors (PARs). We examined the biological actions of human trypsin IV (or mesotrypsin) and rat p23, inhibitor-resistant forms of trypsin. The zymogens trypsinogen IV and pro-p23 were expressed in Escherichia coli and purified to apparent homogeneity. Enteropeptidase cleaved both zymogens, liberating active trypsin IV and p23, which were resistant to soybean trypsin inhibitor and aprotinin. Trypsin IV cleaved N-terminal fragments of PAR(1), PAR(2), and PAR(4) at sites that would expose the tethered ligand (PAR(1) = PAR(4) > PAR(2)). Trypsin IV increased [Ca(2+)](i) in transfected cells expressing human PAR(1) and PAR(2) with similar potencies (PAR(1), 0.5 microm; PAR(2), 0.6 microm). p23 also cleaved fragments of PAR(1) and PAR(2) and signaled to cells expressing these receptors. Trypsin IV and p23 increased [Ca(2+)](i) in rat dorsal root ganglion neurons that responded to capsaicin and which thus mediate neurogenic inflammation and nociception. Intraplantar injection of trypsin IV and p23 in mice induced edema and granulocyte infiltration, which were not observed in PAR (-/-)(1)(trypsin IV) and PAR (-/-)(2) (trypsin IV and p23) mice. Trypsin IV and p23 caused thermal hyperalgesia and mechanical allodynia and hyperalgesia in mice, and these effects were absent in PAR (-/-)(2) mice but maintained in PAR (-/-)(1) mice. Thus, trypsin IV and p23 are inhibitor-resistant trypsins that can cleave and activate PARs, causing PAR(1)- and PAR(2)-dependent inflammation and PAR(2)-dependent hyperalgesia.

Mesomorphic behaviour in copoly(ester-imide)s of poly(butylene-2,6-naphthalate) (PBN)

Copolycondensation of N,N’-bis(4-hydroxybutyl)-biphenyl-3,4,3',4'-tetracarboxylic diimide at 20 and 25 mol% with bis(4-hydroxybutyl)-2,6-naphthalate produces PBN-based copoly(ester-imide)s that not only crystallise but also form a (smectic) mesophase upon cooling from the melt. Incorporation of 25 mol% imide in PBN causes the glass transition temperature (measured by DSC) to rise from 51 to 74 °C, a significant increase relative to PBN. Furthermore, increased storage- (G'), loss- (G'') and elastic (E) moduli are observed for both copoly(ester-imide)s when compared to PBN itself. Structural analysis of the 20 mol% copolymer by X-ray powder and fibre diffraction, interfaced to computational modelling, suggests a crystal structure related to that of α-PBN, in space group P-1, with cell dimensions a = 4.74, b = 6.38, c = 14.45 Å, α = 106.1, β = 122.1, γ = 97.3°, ρ = 1.37 g cm-3.

Chemistry and structure by design: ordered CuNi(CN)4 sheets with copper(II) in a square-planar environment

Layered copper–nickel cyanide, CuNi(CN)4, a 2-D negative thermal expansion material, is one of a series of copper(II)-containing cyanides derived from Ni(CN)2. In CuNi(CN)4, unlike in Ni(CN)2, the cyanide groups are ordered generating square-planar Ni(CN)4 and Cu(NC)4 units. The adoption of square-planar geometry by Cu(II) in an extended solid is very unusual.

Using U0126 to dissect the role of the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade in the regulation of gene expression by endothelin-1 in cardiac myocytes

The hypertrophic agonist endothelin-1 rapidly but transiently activates the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade (and other signalling pathways) in cardiac myocytes, but the events linking this to hypertrophy are not understood. Using Affymetrix rat U34A microarrays, we identified the short-term (2-4 h) changes in gene expression induced in neonatal myocytes by endothelin-1 alone or in combination with the ERK1/2 cascade inhibitor, U0126. Expression of 15 genes was significantly changed by U0126 alone, and expression of an additional 78 genes was significantly changed by endothelin-1. Of the genes upregulated by U0126, four are classically induced through the aryl hydrocarbon receptor (AhR) by dioxins suggesting that U0126 activates the xenobiotic response element in cardiac myocytes potentially independently of effects on ERK1/2 signalling. The 78 genes showing altered expression with endothelin-1 formed five clusters: (i) three clusters showing upregulation by endothelin-1 according to time course (4 h > 2 h; 2 h > 4 h; 2 h approximately 4 h) with at least partial inhibition by U0126; (ii) a cluster of 11 genes upregulated by endothelin-1 but unaffected by U0126 suggesting regulation through signalling pathways other than ERK1/2; (iii) a cluster of six genes downregulated by endothelin-1 with attenuation by U0126. Thus, U0126 apparently activates the AhR in cardiac myocytes (which must be taken into account in protracted studies), but careful analysis allows identification of genes potentially regulated acutely via the ERK1/2 cascade. Our data suggest that the majority of changes in gene expression induced by endothelin-1 are mediated by the ERK1/2 cascade.

Role of glutaredoxin 2 and cytosolic thioredoxins in cysteinyl-based redox modification of the 20S proteasome

The yeast 20S proteasome is subject to sulfhydryl redox alterations, such as the oxidation of cysteine residues (Cys-SH) into cysteine sulfenic acid (Cys-SOH), followed by S-glutathionylation (Cys-S-SG). Proteasome S-glutathionylation promotes partial loss of chymotrypsin-like activity and post-acidic cleavage without alteration of the trypsin-like proteasomal activity. Here we show that the 20S proteasome purified from stationary-phase cells was natively S-glutathionylated. Moreover, recombinant glutaredoxin 2 removes glutathione from natively or in vitro S-glutathionylated 20S proteasome, allowing the recovery of chymotrypsin-like activity and post-acidic cleavage. Glutaredoxin 2 deglutathionylase activity was dependent on its entry into the core particle, as demonstrated by stimulating S-glutathionylated proteasome opening. Under these conditions, deglutathionylation of the 20S proteasome and glutaredoxin 2 degradation were increased when compared to non-stimulated samples. Glutaredoxin 2 fragmentation by the 20S proteasome was evaluated by SDS-PAGE and mass spectrometry, and S-glutathionylation was evaluated by either western blot analyses with anti-glutathione IgG or by spectrophotometry with the thiol reactant 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole. It was also observed in vivo that glutaredoxin 2 was ubiquitinated in cellular extracts of yeast cells grown in glucose-containing medium. Other cytoplasmic oxido-reductases, namely thioredoxins 1 and 2, were also active in 20S proteasome deglutathionylation by a similar mechanism. These results indicate for the first time that 20S proteasome cysteinyl redox modification is a regulated mechanism coupled to enzymatic deglutathionylase activity.

Diruthenium(II, III) complexes of ibuprofen, aspirin, naproxen and indomethacin non-steroidal anti-inflammatory drugs: Synthesis, characterization and their effects on tumor-cell proliferation

[Ru-2(dNSAID)(4)Cl] and novel [Ru-2(dNSAID)(4)(H2O)(2)]PF6 complexes, where dNSAID = deprotonated carboxylate from the non-steroidal anti-inflammatory drugs (NSIDs), respectively: ibuprofen, Hibp (1) and aspirin, Hasp (2); naproxen, Hnpx (3) and indomethacin, Hind (4), have been prepared and characterized by optical spectroscopic methods. All of the compounds exhibit mixed valent Ru-2(II, III) cores where metal-metal bonds are stabilized by four drug-carboxylate bridging ligands in paddlewheel type structures. The diruthenium complexes and their parent NSAIDs showed no significant effects for Hep2 human larynx or T24/83 human bladder tumor. In contrast, the coordination of Ru-2(II,III) core led to synergistic effects that increased significantly the inhibition of C6 rat glioma proliferation in relation to the organic NSAIDs naproxen and ibuprofen, The possibility that the complexes Ru-2-ibp and Ru-2-npx may exert effects (anti-angiogenic and anti-matrix metalloprotease) that are similar to those exhibited by NAMI-A opens new horizons for in vivo C6 glioma model studies. (C) 2007 Elsevier Ltd. All rights reserved.

The mer-[RuCl(3)(dppb)(H(2)O)] complex: A versatile tool for synthesis of Ru(II) compounds

The complex mer-[RuCl(3)(dppb)(H(2)O)] [dppb = 1,4-bis(diphenylphosphino)butane] was used as a precursor in the synthesis of the complexes tc-[RuCl(2)(CO)(2)(dppb)], ct-[RuCl(2)(CO)(2)(dppb)]. cis-[RuCl(2)(dppb)(Cl-bipy)], [RuCl(2Ac4mT)(dppb)] (2Ac4mT = N(4)-meta-tolyl-2-acetylpyridine thiosemicarbazone ion) and trans-[RuCl(2)(dppb)(mang)] (mang = mangiferin or 1,3,6,7-tetrahydroxyxanthone-C2-beta-D-glucoside) complexes. For the synthesis of Run complexes, the Ru(III) atom in mer-[RuCl(3)(dppb)(H(2)O)] may be reduced by H(2)(g), forming the intermediate [Ru(2)Cl(4)(dppb)(2)], or by a ligand (such as H2Ac4mT or mangiferin). The X-ray structures of the cis-[RuCl(2)(dppb)(Cl-bipy)], tc-[RuCl(2)(CO)(2)(dppb)] and [RuCl(2Ac4mT)(dPpb)] complexes were determined. (C) 2010 Elsevier Ltd. All rights reserved.

Structure and thermal reactivity of Zn(II) salts of isocinchomeronic acid (2,5-pyridinedicarboxylic acid)

The synthesis, an improved refined crystal and molecular structure re-determination, and the thermal decomposition behavior of two Zn(II) derivatives of isocinchomeronic acid (2,5-pyridinedicarboxylic acid or H(2)2,5-pydc) are presented. [Zn(2,5-pydc)(H(2)O)(3)Zn(2,5-pydc)(H(2)O)(2)](2) (1) crystallizes in the triclinic P-1 space group with a = 7.106(2), b = 11.450(2), c = 11.869(1) angstrom, alpha = 107.29(1), beta = 104.08(1), gamma = 90.32(2)degrees, and Z = 2. [Zn(2,5-pydc)(H(2)O)(2)] center dot H(2)O (2) is orthorhombic (P2(1)2(1)2(1) space group), with a = 7.342(1), b = 9.430(1), c = 13.834(2) angstrom, and Z = 4. The structures were refined to agreement R(1)-factors of 0.0315 (1) and 0.0336 (2). Complex (1) is arranged as molecular Zn(4)(2,5-pydc)(4)(H(2)O)(10) tetramers, the cages of which define channels that remain unblocked by anions. Compound (2) is polymeric with Zn(2,5-pydc)(H(2)O)(2) and Zn(2,5-pydc)(H(2)O)(3) units linked through bridging ligands. Both compounds were synthesized under mild conditions in aqueous media, without need to resort to hydrothermal media. Changing the pH from 4.51 to 5.75 suffices to direct the chemical processes toward the orthorhombic compound rather than to the triclinic one.