Synthesis and isocyanate insertion reactions of tungsten(IV) imido complexes formed from W(CO)(acac)(N3)(PMe3)3 with azide as the oxidant

Addition of excess trimethylphosphine and a halide source to a solution of W(CO)(acac)₂(η²-L) (L = NCPh and OCMe₂) leads to displacement of L and one acetylacetonate chelate to produce electron-rich, seven-coordinate complexes of the formula W(CO)(acac)(X)(PMe₃)₃ (X = Cl, Br, and I). Use of NaN₃ instead of a halide source leads primarily to loss of carbon monoxide and dinitrogen, and protonation from adventitious water yields the cationic imido complex [W(NH)(acac)(PMe₃)₃]⁺. Heating [W(NH)(acac)(PMe₃)₃]⁺ in aromatic isocyanates at high temperature results in isocyanate insertion into the NH imido bond to form new C-N bonds. An alternate route to related imido complexes involves heating [W(O)(acac)(PMe₃)₃]⁺ with phenyl isocyanate at high temperatures to yield the substituted imido complex [W(NPh)(acac)(PMe₃)₃]⁺.     

Comparative Pathology and Ecological Implications of Two Myxosporean Parasites in Native Australian Frogs and the Invasive Cane Toad

Myxosporean parasites Cystodiscus axonis and C. australis are pathogens of native and exotic Australian frog species. The pathology and ecological outcomes of infection with these parasites were investigated in this study. Gliosis was correlated to Cystodiscus axonis plasmodia in the brains of (9/60) tadpoles and (3/9) adult endangered Green and golden bell frogs using ordinal regression. Severe host reactions to C. axonis (haemorrhage, necrosis, and vasulitis) were observed in the brains of threatened Southern bell frogs (8/8), critically endangered Booroolong frogs (15/44) and Yellow spotted bell frogs (3/3). Severe brain lesions were associated with behavioural changes, neurological dysfunction, and spontaneous death. Both C. axonis and C. australis develop in the bile ducts of tadpoles, the plasmodia were significantly associated with biliary hyperplasia, inflammation and the loss of hepatocytes in (34/72) Green and golden bell frog tadpoles using ordinal regression. These lesions were so severe that in some cases 70% of the total liver was diseased. Normal liver function in tadpoles is necessary for metamorphosis, metabolism, and immune function. We postulate that this extensive liver damage would have significant host health impacts. Severe hepatic myxosporidiosis was more prevalent in tadpoles examined in autumn and winter (overwintered), suggestive of delayed metamorphosis in infected tadpoles, which would have serious flow-on effects in small populations. We compared the sensitivity of histopathology and species-specific PCR in the detection of C. australis and C. axonis. PCR was determined to be the most sensitive method (detection limit 1 myxospore equivalent of ribosomal DNA). Histology, however, had the advantage of assessing the impact of the parasite on the host. It was concluded that these parasites have the potential for significant ecological impacts, because of their high prevalence of infection and their ability to cause disease in some frogs.     

Novel 2,4-dichlorophenoxy acetic acid substituted thiazolidin-4-ones as anti-inflammatory agents: Design,synthesis and biological screening

A library of fourteen 2-imino-4-thiazolidinone derivatives (1a-1n) has been synthesized and evaluated for in vivo anti-inflammatory activity and effect on ex-vivo COX-2 and TNF–α expression. Compounds 1k (5-(2,4-dichloro-phenooxy)-acetic acid (3-benzyl-4-oxo-thiazolidin-2-ylidene)-hydrazide) and 1m (5-(2,4-dichloro-phenooxy)-acetic acid (3-cyclohexyl-4-oxo-thiazolidin-2-ylidene)-hydrazide) exhibited in vivo inhibition of 81.14% and 78.80% respectively after 5 h in comparison to indomethacin which showed 76.36% inhibition of inflammation without causing any damage to the stomach. Compound 1k showed a reduction of 68.32% in the level of COX-2 as compared to the indomethacin which exhibited 66.23% inhibition of COX-2. The selectivity index of compound 1k was found to be 29.00 in comparison to indomethacin showing selectivity index of 0.476. Compounds 1k and 1m were also found to significantly suppress TNF-α concentration to 70.10% and 68.43% in comparison to indomethacin which exhibited 66.45% suppression.     

Oxidative stress in zinc-induced dopaminergic neurodegeneration: implications of superoxide dismutase and heme oxygenase-1

The study was undertaken to investigate the effect of zinc (Zn) on glutathione S-transferase (GST) and superoxide dismutases (SOD) activities and on the expressions of cytosolic Cu, Zn-SOD (SOD1), mitochondrial Mn-SOD (SOD2), γ-glutamyl cysteine synthetase (γ-GCS) and heme oxygenase-1 (HO-1) in the nigrostriatal tissue of rats. Additionally, Zn-induced alterations in the neurobehavioral parameters, lipid peroxidation (LPO), striatal dopamine and its metabolites and tyrosine hydroxylase (TH) protein expression were measured to assess their correlations with the oxidative stress. Zn exposure reduced the locomotor activity, rotarod performance, striatal dopamine and its metabolites and TH protein expression. LPO, total SOD, SOD1 and SOD2 activities were increased while GST and catalase were reduced in a dose and time dependent manner. Expressions of SOD1 and HO-1 were increased while no change was observed in SOD2 and γ-GCS expressions. The results obtained suggest that Zn-induced augmentation of total SOD, SOD1, SOD2 and HO-1 was associated with increased oxidative stress and neurodegenerative indexes indicating the involvement of both cytosolic and mitochondrial machinery in Zn-induced oxidative stress leading to dopaminergic neurodegeneration.     

Is dipalmitoylphosphatidylcholine a substrate for convertase?

Convertase has homology with carboxylesterases, but its substrate(s) is not known. Accordingly, we determined whether dipalmitoylphosphatidylcholine (DPPC), the major phospholipid in surfactant, was a substrate for convertase. We measured [(3)H]choline release during cycling of the heavy subtype containing [(3)H]choline-labeled DPPC with convertase, phospholipases A(2), B, C, and D, liver esterase, and elastase. Cycling with liver esterase or peanut or cabbage phospholipase D produced the characteristic profile of heavy and light peaks observed on cycling with convertase. In contrast, phospholipases A(2), B, and C and yeast phospholipase D produced a broad band of radioactivity across the gradient without distinct peaks. [(3)H]choline was released when natural surfactant containing [(3)H]choline-labeled DPPC was cycled with yeast phospholipase D but not with convertase or peanut and cabbage phospholipases D. Similarly, yeast phospholipase D hydrolyzed [(3)H]choline from [(3)H]choline-labeled DPPC after incubation in vitro, whereas convertase, liver esterase, or peanut and cabbage phospholipases D did not. Thus convertase, liver esterase, and plant phospholipases D did not hydrolyze choline from DPPC either on cycling or during incubation with enzyme in vitro. In conclusion, conversion of heavy to light subtype of surfactant by convertase may require a phospholipase D type hydrolysis of phospholipids, but the substrate in this reaction is not DPPC.