Regioregular improvement on the oxidative polymerization of poly-3-octylthiophenes by slow addition of oxidant at low temperature

Many pathways can be used to synthesize polythiophenes derivatives. The polycondensation reactions performed with organometallics are preferred since they lead to regioregular polymers (with high content of heat-to-tail coupling) which have enhanced conductivity and luminescence. However, these pathways have several steps; the reactants are highly moisture sensitive and expensive. On the other hand, the oxidative polymerization using FeCl3 is a one-pot reaction that requires less moisture sensitive reactants with lower cost, although the most common reaction conditions lead to polymers with low regioregularity. Here, we report that by changing the reaction conditions, such as FeCl3 addition rate and reaction temperature, poly-3-octylthiophenes with different the regioregularities can be obtained, reaching about 80% of heat-to-tail coupling. Different molar mass distributions and polydispersivities were obtained. The preliminary results suggest that the oxidative polymerization process could be improved to yield polythiophenes with higher regioregularity degree and narrower molar mass distributions by just setting some reaction conditions. We also verified that it is possible to solvent extract part of the lower regioregular fraction of the polymer further improving the regioregularity degree. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Increasing the activity of copper(II) complexes against Leishmania through lipophilicity and pro-oxidant ability

Copper complexes with fluorinated beta-diketones were synthesized and characterized in terms of lipophilicity and peroxide-assisted oxidation of dihydrorhodamine as an indicator of redox activity. The biological activity of the complexes was tested against promastigotes of Leishmania amazonensis. Inhibition of trypanosomatid-specific trypanothione reductase was also tested. It was found that the highly lipophilic and redox-active bis(trifluoroacetylacetonate) derivative had increased toxicity towards promastigotes. These results indicate that it is possible to modulate the activity of metallodrugs based on redox-active metals through the appropriate choice of lipophilic chelators in order to design new antileishmanials. Further work will be necessary to improve selectivity of these compounds against the parasite.

CD40 ligation protects bronchial epithelium against oxidant-induced caspase-independent cell death

CD40 and its ligand regulate pleiotropic biological responses, including cell proliferation, differentiation, and apoptosis. In many inflammatory lung diseases, tissue damage by environmental or endogenous oxidants plays a major role in disease pathogenesis. As the epithelial barrier is a major target for these oxidants, we postulated that CD40, the expression of which is increased in asthma, plays a role in the regulation of apoptosis of bronchial epithelial cells exposed to oxidants. Using 16HBE 14o- cells exposed to oxidant stress, we found that ligation of CD40 (induced by G28-5 monoclonal antibodies) enhanced cell survival and increased the number of cells in G2/M (interphase between DNA synthesis and mitosis) of the cell cycle. This was associated with NF-kappaB and activator protein-1 activation and increased expression of the inhibitor of apoptosis, c-IAP1. However, oxidant stress-induced apoptosis was found to be caspase- and calpain-independent implicating CD40 ligation as a regulator of caspase-independent cell death. This was confirmed by the demonstration that CD40 ligation prevented mitochondrial release and nuclear translocation of apoptosis inducing factor. In conclusion, we demonstrate a novel role for CD40 as a regulator of epithelial cell survival against oxidant stress. Furthermore, we have identified, for the first time, an endogenous inhibitory pathway of caspase-independent cell death.

Proliferation signal inhibitor-induced decrease of vascular endothelial cadherin expression and increase of endothelial permeability in vitro are prevented by an anti-oxidant

BACKGROUND: Rapamycines, sirolimus (SRL) and everolimus (ERL), are proliferation signal inhibitors (PSIs). PSI therapy often leads to edema. We hypothesized that increased oxidative stress in response to PSIs may modulate the expression of vascular endothelial (VE)-cadherin on endothelial cells (ECs) and, subsequently, vascular permeability, which in turn may be involved in the development of edema. METHODS: Experiments were performed on human umbilical vein ECs (HUVECs). Oxidative stress was measured by dichlorofluorescein-diacetate. Expression of VE-cadherin was evaluated by immunofluorescent staining and western blot analysis. Endothelial "permeability" was assessed using a transwell model. RESULTS: SRL and ERL, at concentrations of 1, 10 and 100 nmol/liter, enhanced oxidative stress (SRL: 24 +/- 12%, 29 +/- 9%, 41 +/- 13% [p < 0.05, in all three cases]; ERL: 13 +/- 10%, 27 +/- 2%, 40 +/- 12% [p < 0.05, in the latter two cases], respectively) on HUVECs, which was inhibited by the anti-oxidant, N-acetyl-cysteine (NAC) and, to a lesser extent, by the specific inhibitor of nitric oxide synthase, N-Omega-nitro-L-arginine methylester. By the use of NAC, VE-cadherin expression remained comparable with control, according to both immunocytochemistry and western blot analysis. Permeability was significantly increased by SRL and ERL at 100 nmol/liter (29.5 +/- 6.4% and 33.8 +/- 4.2%, respectively); however, co-treatment with NAC abrogated the increased permeability. CONCLUSIONS: EC homeostasis, as indicated by VE-cadherin expression, may be damaged by SRL and ERL, but resolved by the anti-oxidant NAC.

Compounds that bind to the gamma-aminobutyric acid benzodiazepine ionophore complex modulate the cellular response to oxidant stress

The γ-aminobutyric acid benzodiazepine (GABAA /BZDR) ionophore complex has been widely studied in the central nervous system (CNS) and it regulates Cl− ion movement across the plasma membrane. The complex has been found in the distal tubule and the thick ascending limb of the kidney. The goal of this study was to see if modulation of this complex by agonists or antagonists could affect the way Madin-Darby Canine Kidney (MDCK) cells responded to an oxidant stress induced by menadione. When compared to cells incubated with menadione alone, preincubation with lindane, a nonspecific GABAA antagonist, coincubation with bicuculline, a specific GABAA antagonist, and coincubation with FG7142, an inverse agonist for the BZDR, protected cells from menadione cytotoxicity. Preincubation of cells in media containing PK11195 had no effect on menadione cytotoxicity. Coincubation with flurazepam, a BZDR agonist, exacerbated menadione cytotoxicity. This suggests that modulation of the GABAA/BZDR ionophore complex within MDCK cells with agonists and antagonists can alter the cellular responsiveness to an oxidant-induced injury. These responses via agonists and antagonists may be due to alterations of Cl− ion influx during late stage necrotic cell death. ^

Differential stress response and susceptibility to oxidative injury in alveolar macrophages from C57BL/6J and C3H/HeJ mice following oxidant exposure

Studies have demonstrated a variable response to ozone among individuals and animal species and strains. For instance, C57BL/6J mice have a greater inflammatory response to ozone exposure than C3H/HeJ mice. In these studies, I utilized these strain differences in an effort to derive a mechanistic explanation to the variable strain sensitivity to ozone exposure. Therefore, alveolar macrophages (AM) from C57BL/6J and C3H/HeJ mice were exposed in vitro to hydrogen peroxide ($\rm H\sb2O\sb2$), heat and acetyl ceramide or in vivo to ozone. Necrosis and DNA fragmentation in macrophages from the two murine strains were determined to assess cytotoxicity following these treatments. In addition, synthesis and expression of the stress proteins, stress protein 72 (SP72) and heme oxygenase (HO-1), were examined following treatments. The in vitro experiments were conducted to eliminate the possibility of in vivo confounders (i.e., differences in breathing rates in the two strains) and thus directly implicate some inherent difference between cells from the two murine strains. $\rm H\sb2O\sb2$ and heat caused greater cytotoxicity in AM from C57BL/6J than C3H/HeJ mice and DNA fragmentation was a particularly sensitive indicator of cell injury. Similarly, AM from C57BL/6J mice were more sensitive to ozone exposure than cells from C3H/HeJ mice. Exposure to either 1 or 0.4 ppm ozone caused greater cytotoxicity in macrophages from C57BL/6J mice compared to macrophages from C3H/HeJ mice. The increased sensitivity of AM to injury was associated with decreased synthesis and expression of stress proteins. AM from C57BL/6J mice synthesized and expressed significantly less stress proteins in response to heat and ozone than AM from C3H/HeJ mice. Heat treatment resulted in greater synthesis and expression of SP72. In addition, macrophages from C57BL/6J mice expressed lower amounts of HO-1 than macrophages from C3H/HeJ mice following 0.4 ppm ozone exposure. Therefore, AM from C57BL/6J mice are more susceptible to oxidative injury than AM from C3H/HeJ mice which might be due to differential expression of stress proteins in these cells. ^

The reductive enzyme thioredoxin 1 acts as an oxidant when it is exported to the Escherichia coli periplasm

Thioredoxin 1 is a major thiol-disulfide oxidoreductase in the cytoplasm of Escherichia coli. One of its functions is presumed to be the reduction of the disulfide bond in the active site of the essential enzyme ribonucleotide reductase. Thioredoxin 1 is kept in a reduced state by thioredoxin reductase. In a thioredoxin reductase null mutant however, most of thioredoxin 1 is in the oxidized form; recent reports have suggested that this oxidized form might promote disulfide bond formation in vivo. In the Escherichia coli periplasm, the protein disulfide isomerase DsbC is maintained in the reduced and active state by the membrane protein DsbD. In a dsbD null mutant, DsbC accumulates in the oxidized form. This oxidized form is then able to promote disulfide bond formation. In both these cases, the inversion of the function of these thiol oxidoreductases appears to be due to an altered redox balance of the environment in which they find themselves. Here, we show that thioredoxin 1 attached to the alkaline phosphatase signal sequence can be exported into the E. coli periplasm. In this new environment for thioredoxin 1, we show that thioredoxin 1 can promote disulfide bond formation and, therefore, partially complement a dsbA strain defective for disulfide bond formation. Thus, we provide evidence that by changing the location of thioredoxin 1 from cytoplasm to periplasm, we change its function from a reductant to an oxidant. We conclude that the in vivo redox function of thioredoxin 1 depends on the redox environment in which it is localized.

Corn stover thermal decomposition in pyrolytic and oxidant atmosphere

The pyrolysis and combustion of corn stover were studied by dynamic thermogravimetry and derivate thermogravimetry (TG-DTG) at heating rates of 5, 10, 20 and 50 K min−1 at atmospheric pressure. For the simulation of pyrolysis and combustion processes a kinetic model based on the distribution of activation energies was used, with three pools of reactants (three pseudocomponents) because of the complexity of the biomass samples of agricultural origin. The experimental thermogravimetric data of pyrolysis and combustion processes were simultaneously fitted to determine a single set of kinetic parameters able to describe both processes at the different heating rates. The model proposed achieves a good correlation between the experimental and calculated curves, with an error of less than 4% for fitting four heating rates simultaneously. The experimental results and kinetic parameters may provide useful data for the design of thermo decomposition processing system using corn stover as feedstock. On the other hand, analysis of the main compounds in the evolved gas is given by means of a microcromatograph.

Photochemical oxidant air pollution effects on a mixed conifer forest ecosystem : final report /

Mode of access: Internet.

Vitamin C exhibits pro-oxidant properties

Vitamin C is marketed as a dietary supplement, partly because of its 'antioxidant' properties. However, we report here that vitamin C administered as a dietary supplement to healthy humans exhibits a pro-oxidant, as well as an antioxidant, effect in vivo.

4-hydroxy estradiol-induced oxidant-mediated signaling is involved in the development of breast cancer

Breast cancer is a disease associated with excess exposures to estrogens. While the mode of cancer causation is unknown, others have shown that oxidative stress induced by prolonged exposure to estrogens mediates renal, liver, endometrial and mammary tumorigenesis though the mechanism(s) underling this process is unknown. In this study, we show that 4-hydroxyl 17β-estradiol (4-OHE2), a catechol metabolite of estrogen, induces mammary tumorigenesis in a redox dependent manner. We found that the mechanism of tumorigenesis involves redox activations of nuclear respiratory factor-1 (NRF1); a transcriptions factor associated with regulation of mitochondria biogenesis and oxidative phosphorylation (OXPHOS), as well as mediation of cell survival and growth of cells during periods of oxidative stress. Key findings from our study are as follows: (i) Prolonged treatments of normal mammary epithelial cells with 4-OHE2, increased the formation of intracellular reactive oxygen species (ROS). (ii) Estrogen-induced ROS activates redox sensitive transcription factors NRF1. (iii) 4-OHE2 through activation of serine-threonine kinase and histone acetyl transferase, phosphorylates and acetylate NRF1 respectively. (iv) Redox mediated epigenetic modifications of NRF1 facilitates mammary tumorigenesis and invasive phenotypes of breast cancer cells via modulations of genes involved in proliferation, growth and metastasis of exposed cells. (v) Animal engraftment of transformed clones formed invasive tumors. (vi) Treatment of cells or tumors with biological or chemical antioxidants, as well as silencing of NRF1 expressions, prevented 4-OHE2 induced mammary tumorigenesis and invasive phenotypes of MCF-10A cells. Based on these observations, we hypothesize that 4-OHE2 induced ROS epigenetically activate NRF1 through its phosphorylation and acylation. This, in turn, through NRF1-mediated transcriptional activation of the cell cycle genes, controls 4-OHE2 induced cell transformation and tumorigenesis.^

Multicomponent kinetic spectrophotometric determination of pefloxacin and norfloxacin in pharmaceutical preparations and human plasma samples with the aid of chemometrics

A spectrophotometric method for the simultaneous determination of the important pharmaceuticals, pefloxacin and its structurally similar metabolite, norfloxacin, is described for the first time. The analysis is based on the monitoring of a kinetic spectrophotometric reaction of the two analytes with potassium permanganate as the oxidant. The measurement of the reaction process followed the absorbance decrease of potassium permanganate at 526 nm, and the accompanying increase of the product, potassium manganate, at 608 nm. It was essential to use multivariate calibrations to overcome severe spectral overlaps and similarities in reaction kinetics. Calibration curves for the individual analytes showed linear relationships over the concentration ranges of 1.0–11.5 mg L−1 at 526 and 608 nm for pefloxacin, and 0.15–1.8 mg L−1 at 526 and 608 nm for norfloxacin. Various multivariate calibration models were applied, at the two analytical wavelengths, for the simultaneous prediction of the two analytes including classical least squares (CLS), principal component regression (PCR), partial least squares (PLS), radial basis function-artificial neural network (RBF-ANN) and principal component-radial basis function-artificial neural network (PC-RBF-ANN). PLS and PC-RBF-ANN calibrations with the data collected at 526 nm, were the preferred methods—%RPET not, vert, similar 5, and LODs for pefloxacin and norfloxacin of 0.36 and 0.06 mg L−1, respectively. Then, the proposed method was applied successfully for the simultaneous determination of pefloxacin and norfloxacin present in pharmaceutical and human plasma samples. The results compared well with those from the alternative analysis by HPLC.

Effect of atmospheric ageing on volatility and ROS of biodiesel exhaust nano-particles

Generally, the magnitude of pollutant emissions from diesel engines is ultimately coupled to the structure of fuel molecules. The presence of oxygen, level of unsaturation and the carbon chain length of respective molecules influence the combustion chemistry. It is speculated that increased oxygen content in the fuel may lead to the increased oxidative potential (Stevanovic, S. 2013). Also, upon the exposure to UV and ozone in the atmosphere, the chemical composition of the exhaust is changed. The presence of an oxidant and UV is triggering the cascade of photochemical reactions as well as the partitioning of semi-volatile compounds between the gas and particle phase. To gain an insight into the relationship between the molecular structures of the esters, their volatile organic content and the potential toxicity of diesel exhaust particulate matter, measurements were conducted on a modern common rail diesel engine. This research also investigates the contribution of atmospheric conditions on the transfer of semi-volatile fraction of diesel exhaust from the gas phase to the particle phase and the extent to which semi-volatile compounds (SVOCs) are related to the oxidative potential, expressed through the concentration of reactive oxygen species (ROS) (Stevanovic, S. 2013)...

Desorption electrospray ionisation mass spectrometry reveals in situ modification of a hindered amine light stabiliser resulting from direct N–OR bond cleavage

Detection and characterisation of structural modifications of a hindered amine light stabiliser (HALS) directly from a polyester-based coil coating have been achieved by desorption electrospray ionisation mass spectrometry (DESI-MS) for the first time. In situ detection is made possible by exposing the coating to an acetone vapour atmosphere prior to analysis. This is a gentle and non-destructive treatment that allows diffusion of analyte to the surface without promoting lateral migration. Using this approach a major structural modification of the HALS TINUVIN®123 (bis(1-octyloxy-2,2,6,6-tetramethyl-4-piperidyl) sebacate) was discovered where one N-ether piperidine moiety (N-OC8H17) is converted to a secondary piperidine (N–H). With the use of 2-dimensional DESI-MS imaging the modification was observed to arise during high curing temperatures (ca. 260 °C) and under simulated physiological conditions (80 °C, full solar spectrum). It is proposed that the secondary piperidine derivative is a result of a highly reactive aminyl radical intermediate produced by N–O homolytic bond cleavage. The nature of the bond cleavage is also suggested by ESR spin-trapping experiments employing α-phenyl-N-tert-butyl nitrone (PBN) in toluene at 80 °C. The presence of a secondary piperidine derivative in situ and the implication of N–OR competing with NO–R bond cleavage suggest an alternative pathway for generation of the nitroxyl radical—an essential requirement in anti-oxidant activity that has not previously been described for the N-ether sub-class of HALS.