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Rationale: The expression of osteocalcin is augmented in human atherosclerotic lesions. How osteocalcin triggers vascular pathogenesis and remodeling is unclear. Objective: To investigate whether osteocalcin promotes transformation of adventitial fibroblast to myofibroblasts and the molecular mechanism involved. Methods and Results: Immunohistochemistry indicated that osteocalcin was expressed in the neointima of renal arteries from diabetic patients. Western blotting and wound-healing assay showed that osteocalcin induced fibroblast transformation and migration, which were attenuated by blockers of the renin-angiotensin system and protein kinase Cδ (PKCδ), toll-like receptor 4 (TLR4) neutralizing antibody, and antagonist and inhibitors of free radical production and cyclooxygenase-2. Small interfering RNA silencing of TLR4 and PKCδ abolished fibroblast transformation. Angiotensin II level in the conditioned medium from the osteocalcin-treated fibroblasts was found elevated using enzyme immunoassay. Culturing of fibroblasts in conditioned medium collected from differentiated osteoblasts promoted fibroblast transformation. The expression of fibronectin, TLR4, and cyclooxygenase-2 is augmented in human mesenteric arteries after 5-day in vitro exposure to osteocalcin. Conclusions: Osteocalcin transforms adventitial fibroblasts to myofibroblasts through stimulating angiotensin II release and subsequent activation of PKCδ/TLR4/reactive oxygen species/cyclooxygenase-2 signaling cascade. This study reveals that the skeletal hormone osteocalcin cross-talks with vascular system and contributes to vascular remodeling.

A new mixed-valent silver complex [AgII(tmc)][AgII(tmc)(H2O)]2·[AgI11(C2)(CF3CO2)12(H2O)4]2 (tmc=1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) was synthesized by adding tmc to a concentrated aqueous solution of silver trifluoroacetate containing dissolved silver acetylide. Single-crystal X-ray analysis revealed that the resulting [AgII(tmc)]2+ and [AgII(tmc)(H2O)]2+ complex cations induce the self-assembly of a centrosymmetric anionic cluster dimer from the Ag(I), C22− and CF3CO2− species. A new type of cluster core [C2@Ag8]Ag was observed, which takes the form of a bicapped trigonal prism with a pendant silver atom attached to one edge.

Aims: The role of endothelium-derived contracting factors (EDCFs) in regulating renovascular function is yet to be elucidated in renovascular hypertension (RH). The current study investigated whether oxidative stress-dependent cyclooxygenase (COX)-2-derived prostaglandin F2α (PGF2α) impairs endothelial function in renal arteries of renovascular hypertensive rats (RHR). Results: Renal hypertension was induced in rats by renal artery stenosis of both kidneys using the 2-kidney 2-clip model. Acute treatment with reactive oxygen species (ROS) scavengers, COX-2 inhibitors, and thromboxane-prostanoid receptor antagonists, but not COX-1 inhibitors, improved endothelium-dependent relaxations and eliminated endothelium-dependent contractions in RHR renal arteries. Five weeks of treatment with celecoxib or tempol reduced blood pressure, increased renal blood flow, and restored endothelial function in RHRs. Increased ROS production in RHR arteries was inhibited by ROS scavengers, but unaffected by COX-2 inhibitors; whereas increased PGF2α release was reduced by both ROS scavengers and COX-2 inhibitors. ROS also induced COX-2-dependent contraction in RHR renal arteries, which was accompanied by the release of COX-2-derived PGF2α. Further, chronic tempol treatment reduced COX-2 and BMP4 upregulation, p38MAPK phosphorylation, and the nitrotyrosine level in RHR renal arteries. Conclusion: These findings demonstrate the functional importance of oxidative stress, which serves as an initiator of increased COX-2 activity, and that COX-2-derived PGF2α plays an important role in mediating endothelial dysfunction in RH. Innovation: The current study, thus, suggests that drugs targeting oxidative stress-dependent COX-2-derived PGF2α may be useful in the prevention and management of RH. Antioxid. Redox Signal. 16, 363–373.

Reactions of the pyridine-functionalized lithium alkyls LiRn [R1  CH(SiMe3)C5H4N-2, R2  C(SiMe3) 2C5H4N-2] with nickelocenes Ni(CpR)2[CpR = η5-C5H5 or η5-C5H3(SiMe3)2] gave thermally stable cyclopentadienylnickel alkyl complexes [CpRNiRn]. The reaction of LiR1 with NiCl2 afforded the coupled organic product (R1)2. The crystal structures of [{η5-C5H5} Ni{C(SiMe 3 ) 2 -C 5 H 4 N -2}][NiCα = 2.018(2), NiN = 1.856(2) A] and the coupled organic product {CH(SiMe3)C5H4N-2}2 have been determined.

A series of N₂O₂ tripodal tetradentate ligands derived from di-/tetra-tert-butyl substituted 2-[bis(2-hydroxybenzyl)aminomethyl]X (X = pyridine and benzimidazole) (H₂L(n) (n = 1-4)) and 8-[bis(3,5-di-tert-butyl-2-hydroxybenzyl)]aminoquinoline (H₂L⁵) were synthesised through a 4-step reaction scheme involving sequential formylation, reduction, bromination and alkylation. Treatment of H₂L(n) (n = 1-5) with [WO₂Cl₂(dme)] (dme = 1,2-dimethoxyethane) in the presence of triethylamine gave the corresponding cis-dioxotungsten(VI) complexes [WO₂(L(n))] (n = 1-5). The corresponding molybdenum analogues [MoO₂(L(n))] (n = 1-5) were also prepared from the reaction of [MoO₂(acac)₂] (acac = acetylacetonate) with H₂L(n) (n = 1-3) or [MoO₂Cl₂(dme)] (dme = 1,2-dimethoxyethane) with H₂L(n) (n = 4 and 5). All these compounds were fully characterised by a wide range of spectroscopic methods. The molecular structures of [MoO₂(L(n))] (n = 2, 4) and [WO₂(L²)] were also confirmed by single-crystal X-ray diffraction analysis. The catalytic activities of [MO₂(L(n))] (M = Mo, W; n = 1-4) towards epoxidation of styrene were also examined.

The solid compound formulated as [Mn(4,4′-bpy)2(H2O)4][ClO4]2·(4,4′-bpy)4 (bpy = bipyridine) has been shown by single-crystal structural analysis to be a three-dimensional network with triangular channels, which are constructed by mononuclear [Mn(4,4′-bpy)2(H2O)4]2+ cations and 4,4′-bpy molecules through extensive hydrogen-bonds and π–π interactions.

Treatment of IrCl(3)x H(2)O with one equivalent of 4,4'-di-tert-butyl-2,2'-bipyridyl (dtbpy) in N,N-dimethylformamide (dmf) afforded [IrCl(3)(dmf)(dtbpy)] (1). Alkylation of 1 with Me(3)SiCH(2)MgCl resulted in C--Si cleavage of the Me(3)SiCH(2) group and formation of the Ir(III) silyl dialkyl compound [Ir(CH(2)SiMe(3))(dtbpy)(Me)(SiMe(3))] (2), which reacted with tBuNC to afford [Ir(tBuNC)(CH(2)SiMe(3))(dtbpy)(Me)(SiMe(3))] ([2(tBuNC)]). Reaction of 2 with phenylacetylene afforded dimeric [{Ir(C[triple chemical bond]CPh)(dtbpy)(SiMe(3))}(2)(mu-C[triple chemical bond]CPh)(2)] (3), in which the bridging PhC[triple chemical bond]C(-) ligands are bound to Ir in a mu-sigma:pi fashion. Alkylation of 1 with PhMe(2)CCH(2)MgCl afforded the cyclometalated compound [Ir(dtbpy)(CH(2)CMe(2)C(6)H(4))(2-C(6)H(4)CMe(3))] (4), which features an agostic interaction between the Ir center and the 2-tert-butylphenyl ligand. The cyclic voltammogram of 4 in CH(2)Cl(2) shows a reversible Ir(IV)-Ir(III) couple at about 0.02 V versus ferrocenium/ferrocene. Oxidation of 4 in CH(2)Cl(2) with silver triflate afforded an Ir(IV) species that exhibits an anisotropic electron paramagnetic resonance (EPR) signal in CH(2)Cl(2) glass at 4 K with g( parallel)=2.430 and g( perpendicular)=2.110. Protonation of 4 with HCl and p-toluenesulfonic acid (HOTs) afforded [{Ir(dtbpy)(CH(2)CMe(2)Ph)Cl}(2)(mu-Cl)(2)] (5) and [Ir(dtbpy)(CH(2)CMe(2)Ph)(OTs)(2)] (6), respectively. Reaction of 5 with Li[BEt(3)H] gave the cyclometalated complex [{Ir(dtbpy)(CH(2)CMe(2)C(6)H(4))}(2)(mu-Cl)(2)] (7). Reaction of 4 with tetracyanoethylene in refluxing toluene resulted in electrophilic substitution of the iridacycle by C(2)(CN)(3) with formation of [Ir(dtbpy)(CH(2)CMe(2)C(6)H(3){4-C(2)(CN)(3)})(2-C(6)H(4)CMe(3))] (8). Reaction of 4 with diethyl maleate in refluxing toluene gave the iridafuran compound [Ir(dtbpy)(CH(2)CMe(2)C(6)H(4)){kappa(2)(C,O)-C(CO(2)Et)CH(CO(2)Et)}] (9). Treatment of 9 with 2,6-dimethylphenyl isocyanide (xylNC) led to cleavage of the iridafuran ring and formation of [Ir(dtbpy)(CH(2)CMe(2)C(6)H(4)){C(CO(2)Et)CH(CO(2)Et)}(xylNC)] (10). Protonation of 9 with HBF(4) afforded the dinuclear neophyl complex [(Ir(dtbpy)(CH(2)CMe(2)Ph){kappa(2)(C,O)-C(CO(2)Et)CH(CO(2)Et)})(2)][BF(4)](2) (11). The solid-state structures of complexes 2-5 and 8-11 have been determined.

The air-sensitive bis(micro-iodo)dicopper(I) complex 1 supported by [N-(3,5-di-tert-butyl-2-hydroxybenzyl)-N,N-di-(2-pyridylmethyl)]amine (L) has been prepared by treating copper(I) iodide with L in anhydrous THF. Compound 1 crystallizes as a dimer in space group C2/c. Each copper(I) center has distorted tetrahedral N2I2 coordination geometry with Cu-N(pyridyl) distances 2.061(3) and 2.063(3) A, Cu-I distances 2.6162(5) and 2.7817(5) and a Cu...Cu distance of 2.9086(8) A. Complex 1 is rapidly oxidized by dioxygen in CH2Cl2 with a 1 : 1 stoichiometry giving the bis(micro-iodo)peroxodicopper(II) complex [Cu(L)(micro-I)]2O2 (2). The reaction of 1 with dioxygen has been characterized by UV-vis, mass spectrometry, EPR and Cu K-edge X-ray absorption spectroscopy at low temperature (193 K) and above. The mass spectrometry and low temperature EPR measurements suggested an equilibrium between the bis(micro-iodo)peroxodicopper(II) complex 2 and its dimer, namely, the tetranuclear (peroxodicopper(II))2 complex [Cu(L)(micro-I)]4O4 (2'). Complex 2 undergoes an effective oxo-transfer reaction converting PPh3 into O=PPh3 under anaerobic conditions. At sufficiently high concentration of PPh3, the oxygen atom transfer from 2 to PPh3 was followed by the formation of [Cu(PPh3)3I]. The dioxygen reactivity of 1 was compared with that known for other halo(amine)copper(I) dimers.

Dimeric [Cu2(PPh2Me)4(µ,η1-CCPh)2] has been synthesized and crystallographically characterized; its photophysics together with those of other related organocopper(I) complexes, [Cu2{2-C(SiMe3)2C5H4N}2] and [{Cu(C6H2Me3-2,4,6)}5] have been studied and Stern–Volmer quenching data of the phosphorescent state of the pyridine complex with organic halides are suggestive of a charge-transfer mechanism with a high driving-force regime.

The thermally stable iron(II) dialkyl, 1 was obtained in good yield from [LiR] 2 and FeCl 2 . Reaction of 1 with ArSH yielded the novel neutral mononuclear iron(II) dithiolate complex 2 . An X-ray diffraction study revealed that the alkyl ligands in 1 are bonded to the metal center in a chelating manner, whereas in 2 one alkyl ligand has been converted into a neutral alkane species by ArSH, but remains coordinated to the iron(II) center via its pyridyl nitrogen atom.

Homoleptic Ce(III) and Nd(III) triamides [LnL(3)] [Ln = Ce(1) or Nd(2)] and the heterobimetallic amide-alkoxide derivatives [LnL(2)(mu-OBu(t))2M(tmeda)] [Ln = Ce, M = Na (3); Ln = Nd, M = Na (4); Ln = Nd, M = K (5)] supported by the bulky [N(SiBu(t)Me2)(2-C(5)H(3)N-6-Me)]- ligand (L-) have been successfully synthesized and characterized. Complexes 1-3 and 5 show a high activity toward the ring-opening polymerization of epsilon-caprolactone.

[structure: see text] The synthesis of 1,4,5,8,9,12,13,16-octamethoxytetraphenylene (6) is accomplished in five steps from 3,6-dimethoxy-2-nitroaniline (8). Its inclusion property and the electrochemical data of the corresponding tetraquinone 7 are presented.

The binuclear cobalt(II) amide complex [(CoL2)2-(TMEDA)] (1) [L = N(Si(t)BuMe2)(2-C5H3N-6-Me); TMEDA = Me2NCH2CH2NMe2] has been synthesized by the reaction of anhydrous CoCl2 with 2 equiv of [Li(L)(TMEDA)]. X-ray crystallography revealed that complex 1 consists of two [CoL2] units linked by one TMEDA ligand molecule, which binds in an unusual N,N'-bridging mode. Protolysis of 1 with the bulky phenol Ar(Me)OH (Ar(Me) = 2,6-(t)Bu2-4-MeC6H2) and thiophenol ArSH (Ar = 2,4,6-(t)Bu3C6H2) gives the neutral monomeric cobalt(II) bis(aryloxide) [Co(OAr(Me))2(TMEDA)] (2) and dithiolate [Co(SAr)2(TMEDA)] (3), respectively. Complexes 1-3 have been characterized by mass spectrometry, microanalysis, magnetic moment, and melting-point measurements, in addition to X-ray crystallography.

Electron paramagnetic resonance (EPR) studies of succinate:ubiquinone oxidoreductase (SQR) from Paracoccus denitrificans have been undertaken in the purified and membrane-bound states. Spectroscopic “signatures” accounting for the three iron-sulfur clusters (2Fe-2S, 3Fe-4S, and 4Fe-4S), cytochromeb, flavin, and protein-bound ubisemiquinone radicals have been obtained in air-oxidized, succinate-reduced, and dithionite-reduced preparations at 4–10 K. Spectra obtained at 170 K in the presence of excess succinate showed a signal typical of that of a flavin radical, but superimposed with another signal. The superimposed signal originated from two bound ubisemiquinones, as shown by spectral simulations. Power saturation measurements performed on the air-oxidized enzyme provided evidence for a weak magnetic dipolar interaction operating between the oxidized 3Fe-4S cluster and the oxidized cytochrome b. Power saturation experiments performed on the succinate- and dithionite-reduced forms of the enzyme demonstrated that the 4Fe-4S cluster is coupled weakly to both the 2Fe-2S and the 3Fe-4S clusters. Quantitative interpretation of these power saturation experiments has been achieved through redox calculations. They revealed that a spin-spin interaction between the reduced 3Fe-4S cluster and the cytochrome b (oxidized) may also exist. These findings form the first direct EPR evidence for a close proximity (≤2 nm) of the high potential 3Fe-4S cluster, situated in the succinate dehydrogenase part of the enzyme, and the low potential, low spin b-heme in the membrane anchor of the enzyme.

A series of N2O2 tripodal tetradentate ligands derived from di-/tetra-tert-butyl substituted 2-[bis(2-hydroxybenzyl)aminomethyl]X (X = pyridine and benzimidazole) (H2Ln (n = 1–4)) and 8-[bis(3,5-di-tert-butyl-2-hydroxybenzyl)]aminoquinoline (H2L5) were synthesised through a 4-step reaction scheme involving sequential formylation, reduction, bromination and alkylation. Treatment of H2Ln (n = 1–5) with [WO2Cl2(dme)] (dme = 1,2-dimethoxyethane) in the presence of triethylamine gave the corresponding cis-dioxotungsten(VI) complexes [WO2(Ln)] (n = 1–5). The corresponding molybdenum analogues [MoO2(Ln)] (n = 1–5) were also prepared from the reaction of [MoO2(acac)2] (acac = acetylacetonate) with H2Ln (n = 1–3) or [MoO2Cl2(dme)] (dme = 1,2-dimethoxyethane) with H2Ln (n = 4 and 5). All these compounds were fully characterised by a wide range of spectroscopic methods. The molecular structures of [MoO2(Ln)] (n = 2, 4) and [WO2(L2)] were also confirmed by single-crystal X-ray diffraction analysis. The catalytic activities of [MO2(Ln)] (M = Mo, W; n = 1–4) towards epoxidation of styrene were also examined.

A soluble 2,3,9,10-tetrakis(trimethylsilyl)pentacene (1) was synthesized; the discovery of the radical cationic character of 1 in solution through EPR measurement has provided insights into the sensitivity of acenes towards light and oxygen.

Four copper complexes with hydroxylated bipyridyl-like ligands, namely [Cu(2)(ophen)(2)] (1), [Cu(4)(ophen)(4)(tp)] (2), [Cu(4)(obpy)(4)(tp)] (3), and [Cu(4)(obpy)(4)(dpdc)].2H(2)O (4), (Hophen=2-hydroxy-1,10-phenanthroline, Hobpy=6-hydroxy-2,2'-bipyridine, tp=terephthalate, dpdc=diphenyl-4,4'-dicarboxylate) have been synthesized hydrothermally. X-ray single-crystal structural analyses of these complexes reveal that 1,10-phenanthroline (phen) or 2,2'-bipyridine (bpy) ligands are hydroxylated into ophen or obpy during the reaction, which provides structural evidence for the long-time argued Gillard mechanism. The dinuclear copper(I) complex 1 has three supramolecular isomers in the solid state, in which short copper-copper distances (2.66-2.68 A) indicate weak metal-metal bonding interactions. Each of the mixed-valence copper(i,ii) complexes 2-4 consists of a pair of [Cu(2)(ophen)(2)](+) or [Cu(2)(obpy)(2)](+) fragments bridged by a dicarboxylate ligand into a neutral tetranuclear dumbbell structure. Dinuclear 1 is an intermediate in the formation of 2 and can be converted into 2 in the presence of additional copper(II) salt and tp ligands under hydrothermal conditions. In addition to the ophen-centered pi--pi* excited-state emission, 1 shows strong emissions at ambient temperature, which may be tentatively assigned as an admixture of copper-centered d--s,p and MLCT excited states.