Organoaluminium complexes of ortho-, meta-, para-anisidines: synthesis, structural studies and ROP of ε-caprolactone (and rac-lactide)

Reaction of Me₃Al (two equivalents) with ortho-, meta- or para-anisidine, (OMe)(NH₂)C₆H₄, affords the complexes {[1,2-(OMe),NC₆H₄(μ-Me₂Al)](μ-Me₂Al)}₂ (1), [1,3-(Me₃AlOMe),NHC₆H₄(μ-Me₂Al)]2 (2) or [1,4-(Me₃AlOMe),NHC₆H₄(μ-Me₂Al)]₂ (3), respectively. The molecular structures of 1–3 have been determined and all three complexes were found to be highly active for the ring opening polymerization (ROP) of ε-caprolactone. 1 was found highly active either with or without benzyl alcohol present; at various temperatures, the activity order 1 > 2 ≈ 3 was observed. For the ROP of rac-lactide results for 1–3 were poor

Inhibition of APE1/Ref-1 redox activity rescues human retinal pigment epithelial cells from oxidative stress and reduces choroidal neovascularization

The effectiveness of current treatment for age related macular degeneration (AMD) by targeting one molecule is limited due to its multifactorial nature and heterogeneous pathologies. Treatment strategy to target multiple signaling pathways or pathological components in AMD pathogenesis is under investigation for better clinical outcome. Inhibition of the redox function of apurinic endonuclease 1/redox factor-1 (APE1) was found to suppress endothelial angiogenesis and promote neuronal cell recovery, thereby may serve as a potential treatment for AMD. In the current study, we for the first time have found that a specific inhibitor of APE1 redox function by a small molecule compound E3330 regulates retinal pigment epithelium (RPEs) cell response to oxidative stress. E3330 significantly blocked sub-lethal doses of oxidized low density lipoprotein (oxLDL) induced proliferation decline and senescence advancement of RPEs. At the same time, E3330 remarkably decreased the accumulation of intracellular reactive oxygen species (ROS) and down-regulated the productions of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF), as well as attenuated the level of nuclear factor-κB (NF-κB) p65 in RPEs. A panel of stress and toxicity responsive transcription factors that were significantly upregulated by oxLDL was restored by E3330, including Nrf2/Nrf1, p53, NF-κB, HIF1, CBF/NF-Y/YY1, and MTF-1. Further, a single intravitreal injection of E3330 effectively reduced the progression of laser-induced choroidal neovascularization (CNV) in mouse eyes. These data revealed that E3330 effectively rescued RPEs from oxidative stress induced senescence and dysfunctions in multiple aspects in vitro, and attenuated laser-induced damages to RPE–Bruch׳s membrane complex in vivo. Together with its previously established anti-angiogenic and neuroprotection benefits, E3330 is implicated for potential use for AMD treatment

Evolution of the redox function in mammalian Apurinic/ apyrimidinic endonuclease

Human apurinic/apyrimidinic endonuclease (hApe1) encodes two important functional activities: an essential base excision repair (BER) activity and a redox activity that regulates expression of a number of genes through reduction of their transcription factors, AP-1, NFκB, HIF-1α, CREB, p53 and others. The BER function is highly conserved from prokaryotes (E. coli exonuclease III) to humans (hApe1). Here, we provide evidence supporting a redox function unique to mammalian Apes. An evolutionary analysis of Ape sequences reveals that, of the 7 Cys residues, Cys 93, 99, 208, 296, and 310 are conserved in both mammalian and non-mammalian vertebrate Apes, while Cys 65 is unique to mammalian Apes. In the zebrafish Ape (zApe), selected as the vertebrate sequence most distant from human, the residue equivalent to Cys 65 is Thr 58. The wild-type zApe enzyme was tested for redox activity in both in vitro EMSA and transactivation assays and found to be inactive, similar to C65A hApe1. Substitution of Thr 58 with Cys in zApe, however, resulted in a redox active enzyme, suggesting that a Cys residue in this position is indeed critical for redox function. In order to further probe differences between redox active and inactive enzymes, we have determined the crystal structures of vertebrate redox inactive enzymes, the C65A human Ape1 enzyme and the zApe enzyme at 1.9 and 2.3 Å, respectively. Our results provide new insights on the redox function and highlight a dramatic gain-of-function activity for Ape1 in mammals not found in non-mammalian vertebrates or lower organisms

Vesicular glutamatergic transmission in noise-induced loss and repair of cochlear ribbon synapses

Noise-induced excitotoxicity is thought to depend on glutamate. However, the excitotoxic mechanisms are unknown, and the necessity of glutamate for synapse loss or regeneration is unclear. Despite absence of glutamatergic transmission from cochlear inner hair cells in mice lacking the vesicular glutamate transporter-3

Ethyleneglycol tungsten complexes of calix[6 and 8]arenes: Synthesis, characterization and ROP of ε-caprolactone

By varying the reaction conditions, the reaction of [W(eg)₃] (eg = 1,2-ethanediolato) with p-tert-butylcalix[n]areneHn (n = 6 or 8) in refluxing toluene affords, following work-up, a number of products which have been fully characterized. From the reaction of p-tert-butylcalix[6]areneH₆ with one or two equivalents of [W(eg)₃], only the oxo-bridged complex {[W(eg)]₂(μ-O)p-tert-butylcalix[6]arene} (1) could be isolated, whereas the use of four equivalents of [W(eg)₃], in the presence of molecular sieves, afforded {[W(eg)₂]₂p-tert-butylcalix[6]areneH₂}·2MeCN (2); molecules of 2 pack in bi-layers. Under similar conditions, use of one or two equivalents of [W(eg)₃] and p-tert-butylcalix[8]areneH₈ afforded {[W(eg)]₂p-tert-butylcalix[8]arene}·MeCN (3) in which each tungsten centre was bound by four calixarene oxygens. By contrast, the small orange prisms resulting from the use of four equivalents of [W(eg)₃] and p-tert-butylcalix[8]areneH₈ were shown by synchrotron radiation to be a mixture of two isomers (4a/4b·3.5MeCN). In the major isomer {1,2-[W(eg)₂]₂p-tert-butylcalix[8]areneH₄} (4a), two tungsten centres bind to neighbouring sets of phenolate oxygens, whereas in the minor isomer {1,3-[W(eg)₂]₂p-tert-butylcalix[8]areneH₄} (4b), there is a protonated phenolic group between the two pairs of phenolate oxygens bound to tungsten; the major:minor ratio is about 83:17. Use of p-tert-butyltetrahomodioxacalix[6]areneH₆ with two equivalents of [W(eg)₃] resulted in the isolation of {[WO(eg)]₂p-tert-butyltetrahomodioxacalix[6]areneH₂} (5·0.83toluene·MeCN), in which each dimethyleneoxa bridge is bound to an oxotungsten(VI) centre. Complexes 1–5, together with the known complex [W(eg)p-tert-butylcalix[4]arene] (6), have been screened for their ability to ring open polymerize (ROP) ε-caprolactone; for 1, 2 and 5, 6 conversion rates were good (>88%) at 110 °C over 12 or 24 h, whereas the calix[8]arene complexes 3 and 4 under the same conditions were inactive

Oxidation resistance of graphene-coated Cu and Cu/Ni alloy

The ability to protect refined metals from reactive environments is vital to many industrial and academic applications. Current solutions, however, typically introduce several negative effects, including increased thickness and changes in the metal physical properties. In this paper, we demonstrate for the first time the ability of graphene films grown by chemical vapor deposition to protect the surface of the metallic growth substrates of Cu and Cu/Ni alloy from air oxidation. SEM, Raman spectroscopy, and XPS studies show that the metal surface is well protected from oxidation even after heating at 200 \degree C in air for up to 4 hours. Our work further shows that graphene provides effective resistance against hydrogen peroxide. This protection method offers significant advantages and can be used on any metal that catalyzes graphene growth