Amide-based nonheme cobalt(III) olefin epoxidation catalyst: partition of multiple active oxidants Co(V)=O, Co(IV)=O, and Co(III)-OO(O)CR

A mononuclear nonheme cobalt(III) complex of a tetradentate ligand containing two deprotonated amide moieties, [Co(bpc)Cl(2)][Et(4)N] (1; H(2)bpc = 4,5-dichloro-1,2-bis(2-pyridine-2-carboxamido)benzene), was prepared and then characterized by elemental analysis, IR, UV/Vis, and EPR spectroscopy, and X-ray crystallography. This nonheme Co(III) complex catalyzes olefin epoxidation upon treatment with meta-chloroperbenzoic acid. It is proposed that complex 1 shows partitioning between the heterolytic and homolytic cleavage of an O-O bond to afford Co(V)=O (3) and Co(IV)=O (4) intermediates, proposed to be responsible for the stereospecific olefin epoxidation and radical-type oxidations, respectively. Moreover, under extreme conditions, in which the concentration of an active substrate is very high, the Co-OOC(O)R (2) species is a possible reactive species for epoxidation. Furthermore, partitioning between heterolysis and homolysis of the O-O bond of the intermediate 2 might be very sensitive to the nature of the solvent, and the O-O bond of the Co-OOC(O)R species might proceed predominantly by heterolytic cleavage, even in the presence of small amounts of protic solvent, to produce a discrete Co(V) ?O intermediate as the dominant reactive species. Evidence for these multiple active oxidants was derived from product analysis, the use of peroxyphenylacetic acid as the peracid, and EPR measurements. The results suggest that a less accessible Co(V)=O moiety can form in a system in which the supporting chelate ligand comprises a mixture of neutral and anionic nitrogen donors.     

Nitrile-Containing Fischerindoles from the Cultured Cyanobacterium Fischerella sp

Chemical investigation of the cultured cyanobacterium Fischerella sp. (SAG strain number 46.79) led to the isolation of four nitrile-containing indole alkaloids, namely 12-epi-fischerindole I nitrile (1), deschloro 12-epi-fischerindole I nitrile (2), 12-epi-fischerindole W nitrile (3), and deschloro 12-epi-fischerindole W nitrile (4) along with a known metabolite hapalosin. The structures were determined by detailed spectroscopic analyses on the basis of 1D and 2D NMR and HRESIMS data. All isolates were evaluated for cytotoxicity against human cancer cells and for 20S proteasome inhibition. Deschloro 12-epi-fischerindole I nitrile (2) was found to be weakly cytotoxic against HT-29 cells with an ED(50) value of 23 μM. Hapalosin showed weak cytotoxicity against HT-29 and MCF-7 cells with ED(50) values of 22 and 27 μM, respectively, as well as moderate 20S proteasome inhibition with an IC(50) value of 12 μM. Compounds 1-4 all contain a nitrile moiety instead of the isonitrile found in all fischerindoles reported to date. Compounds 3 and 4 also display a new carbon skeleton, in which a six-membered ring replaces the five-membered ring normally found in fischerindole-type alkaloids.     

Synergy between adiponectin and interleukin-1β on the expression of interleukin-6, interleukin-8, and cyclooxygenase-2 in fibroblast-like synoviocytes

To determine whether adiponectin may have synergistic effects in combination with the proinflammatory cytokine interleukin (IL)-1β regarding the production of proinflammatory mediators during arthritic joint inflammation, synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin, IL-1β, and their combination for 24 h. Culture supernatant was collected and analyzed by enzyme-linked immunosorbent assay for levels of IL-6, IL-8, prostaglandin E(2) (PGE(2)), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Adiponectin-mediated intracellular signaling pathways were investigated to elucidate the molecular mechanisms underlying their synergy. The association of proinflammatory mediators with adiponectin was investigated in the synovial fluid of arthritis patients. Adiponectin functioned synergistically with IL-1β to activate IL-6, IL-8, and PGE2 expression in RA fibroblast-like synoviocytes; Levels of VEGF, MMP-1, and MMP-13 were not synergistically stimulated. Adiponectin and IL-1β each increased the expression of both adiponectin receptor 1 and IL-1 receptor 1. However, adiponectin and IL-1β did not synergistically support the degradation of IκB-α or the nuclear translocation of NF-κB. Synergistically increased gene expression was significantly inhibited by MG132, an NF-κB inhibitor. Supporting the in vitro results, IL-6 and IL-8 levels were positively associated with adiponectin in synovial joint fluid from patients with RA, but not osteoarthritis (OA). In conclusion, adiponectin and IL-1β may synergistically stimulate the production of proinflammatory mediators through unknown signaling pathways during arthritic joint inflammation. Adiponectin may be more important to the pathogenesis of RA than previously thought.     

Surface-plasmon-enhanced band emission of ZnO nanoflowers decorated with Au nanoparticles

A simple strategy was used to enhance band emission through the transfer of defect emission from ZnO to Au by using the energy match between the defect emission of ZnO and the surface plasmon absorbance of Au NPs through decorating the surface of ZnO nanoflowers with Au nanoparticles (Au NPs). The ZnO nanostructure, which was comprised of six nanorods that were attached on one side in a flower-like fashion, was synthesized by using a hydrothermal method. The temperature-dependent morphology and detailed growth mechanism were studied. The influence of the density of the Au NPs that were deposited onto the surface of ZnO on photoluminescence was investigated to optimize the configuration of the ZnO/Au system in terms of the maximum band emission. The sequential transfer of defect energy from ZnO to Au and electron transfer from excited Au to ZnO was proposed as a possible mechanism for the enhanced band emission.     

Analysis of differential plaque depositions in the brains of Tg2576 and Tg-APPswe/PS1dE9 transgenic mouse models of Alzheimer disease

Adequate assessment of plaque deposition levels in the brain of mouse models of Alzheimer disease (AD) is required in many core issues of studies on AD, including studies on the mechanisms underlying plaque pathogenesis, identification of cellular factors modifying plaque pathology, and developments of anti-AD drugs. The present study was undertaken to quantitatively evaluate plaque deposition patterns in the brains of the two popular AD models, Tg2576 and Tg-APPswe/ PS1dE9 mice. Coronally-cut brain sections of Tg2576 and Tg-APPswe/PS1dE9 mice were prepared and plaque depositions were visualized by staining with anti- amyloid β peptides antibody. Microscopic images of plaque depositions in the prefrontal cortex, parietal cortex, piriform cortex and hippocampus were obtained and the number of plaques in each region was determined by a computer-aided image analysis method. A series of optical images representing a gradual increase of plaque deposition levels were selected in the four different brain regions and were assigned in each with a numerical grade of 1-6, where +1 was lowest and +6, highest, so that plaques per unit in mm(2) increased "sigmoidally" over the grading scales. Analyzing plaque depositions using the photographic plaque reference panels and a computer-aid image analysis method, it was demonstrated that the brains of Tg2576 mice started to accumulate predominantly small plaques, while the brains of Tg-APPswe/PS1dE9 mice deposited relatively large plaques.     

Radical 4-exo cyclizations via template catalysis

The mechanism of catalytic 4-exo cyclizations without gem-dialkyl substitution was investigated by a comparison of cyclic voltammetry, EPR, and computational studies with previously published synthetic results. The most active catalyst is a super-unsaturated 13-electron titanocene(III) complex that is formed by supramolecular activation through hydrogen bonding. The template catalyst binds radicals via a two-point binding that is mandatory for the success of the 4-exo cyclization. The computational investigations revealed that formation of the observed trans-cyclobutane product is not possible from the most stable substrate radical. Instead, the most stable product is formed with the lowest energy of activation from a disfavored substrate in a Curtin-Hammett related scenario.     

Structural dynamics of 1,2-diiodoethane in cyclohexane probed by picosecond X-ray liquidography

We investigate the structural dynamics of iodine elimination reaction of 1,2-diiodoethane (C(2)H(4)I(2)) in cyclohexane by applying time-resolved X-ray liquidography (TRXL). The TRXL technique combines structural sensitivity of X-ray diffraction and 100 ps time resolution of X-ray pulses from synchrotron and allows direct probing of transient structure of reacting molecules. From the analysis of time-dependent X-ray solution scattering patterns using global fitting based on DFT calculation and MD simulation, we elucidate the kinetics and structure of transient intermediates resulting from photodissociation of C(2)H(4)I(2). In particular, the effect of solvent on the reaction kinetics and pathways is examined by comparison with an earlier TRXL study on the same reaction in methanol. In cyclohexane, the C(2)H(4)I radical intermediate undergoes two branched reaction pathways, formation of C(2)H(4)I-I isomer and direct dissociation into C(2)H(4) and I, while only isomer formation occurs in methanol. Also, the C(2)H(4)I-I isomer has a shorter lifetime in cyclohexane by an order of magnitude than in methanol. The difference in the reaction dynamics in the two solvents is accounted for by the difference in solvent polarity. In addition, we determine that the C(2)H(4)I radical has a bridged structure, not a classical structure, in cyclohexane.     

Simvastatin inhibits sphingosylphosphorylcholine-induced differentiation of human mesenchymal stem cells into smooth muscle cells

Sphingosylphosphorylcholine (SPC) induces differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) into smooth muscle-like cells expressing α-smooth muscle actin (α-SMA) via transforming growth factor-β1/Smad2- and RhoA/Rho kinase-dependent mechanisms. 3-Hydroxy-3-methylglutaryl- coenzyme A reductase inhibitors (statins) have been known to have beneficial effects in the treatment of cardiovascular diseases. In the present study, we examined the effects of simvastatin on the SPC-induced α-SMA expression and Smad2 phosphorylation in hASCs. Simvastatin inhibited the SPC-induced α-SMA expression and sustained phosphorylation of Smad2 in hASCs. SPC treatment caused RhoA activation via a simvastatin-sensitive mechanism. The SPC-induced α-SMA expression and Smad2 phosphorylation were abrogated by pretreatment of the cells with the Rho kinase inhibitor Y27632 or overexpression of a dominant negative RhoA mutant. Furthermore, SPC induced secretion of TGF-β1 and pretreatment with either Y27632 or simvastatin inhibited the SPC-induced TGF-β1 secretion. These results suggest that simvastatin inhibits SPC-induced differentiation of hASCs into smooth muscle cells by attenuating the RhoA/Rho kinase-dependent activation of autocrine TGF-β1/Smad2 signaling pathway.     

Influence of High-energy electron-beam on photocatalytic activity of TiO2 films on carbon-fiber deposited by atomic layer deposition

High-energy electron-beam with energy of 1 MeV was used for modifying surface structure of TiO₂ thin films on carbon fiber prepared by using atomic layer deposition under atmospheric pressure. TiO₂ nanoparticles (∼20 nm) on carbon fiber underwent structural modification of the surface upon electron-beam treatment, resulting in enhanced photocatalytic activity. In contrast, a thicker film of TiO₂ did not show such changes in surface structure and photocatalytic activity by electron-beam treatment. We demonstrate that electron-beam can be used for modifying surface structure of photocatalysts consisting of nanoparticles for improvement of their activity.