Synthesis, structural characterization and biological properties of cyclometalated iridium(iii) complexes containing 1,2,5]-thiadiazolo-3,4-f]-1,10]-phenanthroline

Two cationic iridium(iii) complexes, Ir(ppy)(2)((tdzp))](+)(1) and Ir(bhq)(2)((tdzp))](+)(2) {ppy = 2-phenylpyridine, bhq = benzoh]quinoline, tdzp = 1,2,5]-thiadiazolo-3,4-f]-1,10]-phenanthroline}, have been synthesized and structurally characterized. The molecular structures of the iridium complexes have been confirmed by single-crystal X-ray structure determination. Extensive hydrogen bonding between lattice water molecules, solvated methanol, and chloride anions is observed in the crystal structure of complex1, which leads to the formation of 1D polymeric cyclic hybrid water-chloride-methanol clusters. The complexes show different photophysical properties in different solvents. The experimental photo-physical properties of the synthesized iridium(iii) complexes match well with the theoretically calculated results obtained by density functional theory (DFT) and time-dependent density functional theory (TD-DFT) studies. The HOMO of complexes1and2is restricted on the iridium and cyclometalated aromatic ligands, while the LUMO, LUMO+1, and LUMO+2 are primarily restricted on the polypyridyl tdzp ligand. The interaction of the complexes with calf thymus DNA (CT-DNA) was investigated by absorption titration and emission titration experiments. Furthermore, the cytotoxicity and cellular localization properties of these complexes towards HeLa cells have been investigated

Fluorophore tagged mixed ligand copper(II) complexes: synthesis, structural characterization, protein binding, DNA cleavage and anticancer activity

Two fluorophore tagged copper(II) complexes Cu(phen)(L)(ClO4)(2)] (1) and Cu(bpy)(L)(H2O)(ClO4)](ClO4) (2), (where L=2-amino-1H-benzode]isoquinoline-1,3-(2H)dione (L), phen=1,10-phenanthroline and bpy=2,2 `-bipyridine) have been synthesized and structurally characterized. Structures of the copper complexes 1 and 2 were confirmed by single-crystal X-ray structure determination. The coordination geometry around the copper center of complexes 1 and 2 is distorted octahedral. The plasmid DNA cleavage activity of the complexes has been investigated by agarose gel electrophoresis and the study reveals that both the complexes have high plasmid DNA photo-cleavage activity. The binding interaction ability of the metal complexes with bovine serum albumin (BSA) was investigated using fluorescence spectroscopy. The cytotoxicity of the complexes has been evaluated by MTT (3-4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide) assay against A549 (adenocarcinoma human alveolar basal epithelial cells) and MCF-7 (breast cancer cell line) cell lines in comparison with cis-platin. Complexes 1 and 2 have exhibited better cytotoxic activity than cis-platin against A549 and MCF-7 cell lines. The cellular uptake study and localization of the complexes within the cells have been investigated by fluorescence microscopy. The cell staining and flow cytometry experiments suggest that complexes induce an apoptotic mode of cell death

A fluoro­phore-labelled copper complex: crystal structure, hybrid cyclic water–perchlorate cluster and biological properties

A fluorophore-labelled copper(II) complex, aquabis(dimethylformamide-O)-(perchlorato-O)[2-(quinolin-2-yl)-1,3-oxazolo[4,5-f][1,10]phenanthroline]cop-per(II) perchlorate monohydrate, [Cu(ClO4)(C22H12N4O)(C3H7NO)2(H2O)]-ClO4H2O, has been synthesized and characterized. A cyclic hydrogen-bondedwater–perchlorate anionic cluster,i.e.[(ClO4)2(H2O)2]2, has been identifiedwithin the structure. Each cyclic anionic cluster unit is interconnected byhydrogen bonding to the cation. The cations join into an infinite hydrogen-bonded chain running in the [010] direction. Furthermore, interaction of thecomplex with calf-thymus DNA (CT-DNA) and cellular localization within thecells was explored. Spectroscopic studies indicate that the compound has a goodaffinity for DNA and stains the nucleus of the cells

Impact of Climate Variability on Groundnut Rust (Puccinia arachidis Speg.) at Hot Semi-Arid Region of Gujarat

Severity of groundnut rust disease caused by pathogen Puccinia arachidis Speg was studied over eight kharif seasons between 2010 and 2020 at Junagadh located in hot semi-arid eco region under agro climatic zone of Gujarat plains and hills. Rust severity was measured on five cultivars (GG 20, GJG 22, TG 37A, TLG 45 and Western 66) grown during three sowing periods (May II fortnight, first and second fortnights of June). Climatic variability for the kharif period of groundnut cultivation was quantified for three climatic variables viz., temperature (maximum and minimum) and rainfall so as to relate to rust severity. The rust progressions in respect of seasons aggregated over cultivars and sowing time on calendar and crop age basis indicated varying duration and severity of the disease. Mean rust severity differed significantly across seasons, cultivars and sowing periods. The rust severity was significantly higher in 2011, GJG 22 and June (both first and second fortnight) sowings, respectively. Although the progression of rust severity varied on calendar as well as crop age basis amongst cultivars, the disease commencement in respect of sowing times was during 34th standard meteorological week (third week of August) coinciding with crop age of eight weeks. Magnitude of climatic variability worked out for kharif of 2011-2020 over long term normals (40 years’ average) indicated a significant change in respect of maximum temperature ( + 0.7 °C) and rainfall ( + 16.9 mm/week). The significant impact of climatic variability on rust severity over seasons indicated positive and negative association of the unchanging minimum temperature and increasing rainfall, respectively. Climate variability impacts on rust severity brought out CJG 22 and TLG 45 as climate resilient cultivars, and sowing groundnut during second fortnight of May as an adaptive practice for recommendation to farmers under the current climate change scenario

Conservation Priority Index of species, communities, and habitats for biodiversity conservation and their management planning: A case study in Gulmarg Wildlife Sanctuary, Kashmir Himalaya

The present study is an attempt to evaluate the Conservation Priority Index (CPI) of species, habitats, and communities for their conservation and management planning in the Kashmir Himalayas in India. The present study is an attempt to prioritize 361 plant species, 18 plant communities (10 within the forest zone and 08 within the alpine zone), and 07 habitats for conservation planning. Out of the total plant species recorded, 06 species were categorized as critically endangered, 20 endangered, 28 vulnerable, and 98 species to be near threatened. Amongst the forest and alpine communities, Abies pindrow community and Juniperus squamata-Rhododendron anthopogon mixed community showed the maximum CPI values. Amongst the habitats, dry habitats showed the maximum CPI in the sanctuary. The study found that the threatened species positively correlated with the native and endemic species indicating that these species were rigorously affected due to biotic and abiotic stresses. Based on the results of the present study, we propose a practical method for biodiversity conservation and management of protected areas. The approach employs a variety of qualitative and quantitative features to compute CPI in conjunction with phytosociological data. This kind of study will be immensely helpful to forest officials, policy makers, conservators, and researchers for planning better strategies to conserve and manage particular species, communities, and even habitats in protected areas

Glycogen synthase kinase-3 inhibition disrupts nuclear factor-kappaB activity in pancreatic cancer, but fails to sensitize to gemcitabine chemotherapy

<p>Abstract</p> <p>Background</p> <p>Aberrant activation NF-kappaB has been proposed as a mechanism of drug resistance in pancreatic cancer. Recently, inhibition of glycogen synthase kinase-3 has been shown to exert anti-tumor effects on pancreatic cancer cells by suppressing NF-kappaB. Consequently, we investigated whether inhibition of GSK-3 sensitizes pancreatic cancer cells to the chemotherapeutic agent gemcitabine.</p> <p>Methods</p> <p>GSK-3 inhibition was achieved using the pharmacological agent AR-A014418 or siRNA against GSK-3 alpha and beta isoforms. Cytotoxicity was measured using a Sulphorhodamine B assay and clonogenic survival following exposure of six different pancreatic cancer cell lines to a range of doses of either gemcitabine, AR-A014418 or both for 24, 48 and 72 h. We measured protein expression levels by immunoblotting. Basal and TNF-alpha induced activity of NF-kappaB was assessed using a luciferase reporter assay in the presence or absence of GSK-3 inhibition.</p> <p>Results</p> <p>GSK-3 inhibition reduced both basal and TNF-alpha induced NF-kappaB luciferase activity. Knockdown of GSK-3 beta reduced nuclear factor kappa B luciferase activity to a greater extent than GSK-3 alpha, and the greatest effect was seen with dual knockdown of both GSK-3 isoforms. GSK-3 inhibition also resulted in reduction of the NF-kappaB target proteins XIAP, Bcl-X_L, and cyclin D1, associated with growth inhibition and decreased clonogenic survival. In all cell lines, treatment with either AR-A014418, or gemcitabine led to growth inhibition in a dose- and time-dependent manner. However, with the exception of PANC-1 where drug synergy occurred with some dose schedules, the inhibitory effect of combined drug treatment was additive, sub-additive, or even antagonistic.</p> <p>Conclusion</p> <p>GSK-3 inhibition has anticancer effects against pancreatic cancer cells with a range of genetic backgrounds associated with disruption of NF-kappaB, but does not significantly sensitize these cells to the standard chemotherapy agent gemcitabine. This lack of synergy might be context or cell line dependent, but could also be explained on the basis that although NF-kappaB is an important mediator of pancreatic cancer cell survival, it plays a minor role in gemcitabine resistance. Further work is needed to understand the mechanisms of this effect, including the potential for rational combination of GSK3 inhibitors with other targeted agents for the treatment of pancreatic cancer.</p

Combined Forward-Backward Asymmetry Measurements in Top-Antitop Quark Production at the Tevatron

The CDF and D0 experiments at the Fermilab Tevatron have measured the asymmetry between yields of forward- and backward-produced top and antitop quarks based on their rapidity difference and the asymmetry between their decay leptons. These measurements use the full data sets collected in proton-antiproton collisions at a center-of-mass energy of $\sqrt s =1.96$ TeV. We report the results of combinations of the inclusive asymmetries and their differential dependencies on relevant kinematic quantities. The combined inclusive asymmetry is $A_{\mathrm{FB}}^{t\bar{t}} = 0.128 \pm 0.025$. The combined inclusive and differential asymmetries are consistent with recent standard model predictions