Differentially Selective Chemosensor with Fluorescence Off-On Responses on Cu2+ and Zn2+ Ions in Aqueous Media and Applications in Pyrophosphate Sensing, Live Cell Imaging, and Cytotoxicity

A new benzoyl hydrazone based chemosensor R is synthesized by Schiff base condensation of 2,6-diformyl-4-methylphenol and phenyl carbohydrazide and acts as a highly selective fluorescence sensor for Cu2+ and Zn2+ ions in aqueous media. The reaction of R with CuCl2 or ZnCl2 forms the corresponding dimeric dicopper(II) Cu-2(R)(CH3O)-(NO3)](2)(CH3O)(2) (R-Cu2+) and dizinc(1) Zn-2(R)(2)](NO3)(2) (R-Zn2+) complexes, which are characterized, as R, by conventional techniques including single-crystal X-ray analysis. Electronic absorption and fluorescence titration studies of R with different metal cations in a CH3CN/0.02 M HEPES buffer medium (pH = 7.3) show a highly selective binding affinity only toward Cu(2+)and Zn2+ ions even in the presence of other commonly coexisting ions such as Ne+, K+, Mg2+, Ca2+, Mn2+, Fe2+, Fe3+, Co2+, Ni2+, Cd2+, and Hg2+. Quantification of the fluorescence titration analysis shows that the chemosensor R can indicate the presence of Cu2+ and Zn2+ even at very low concentrations of 17.3 and 16.5 ppb, respectively. R-Zn2+ acts as a selective metal-based fluorescent sensor for inorganic pyrophosphate ion (PPi) even in the presence of other common anions such as F-, Cl-, Br-, I-, CH3COO-, CO32-, HCO3-, N-3(-), SO42-, PPi, AMP, ADP, and ATP in an aqueous medium. The propensity of R as a bioimaging fluorescent probe to detect Cu2+ and Zn2+ ions in human cervical HeLa cancer cell lines and their cytotoxicity against human cervical (HeLa), breast cancer (MCF7), and noncancer breast epithelial (MCF10a) cells have also been investigated. R-Cu2+ shows better cytotoxicity and sensitivity toward cancer cells over noncancer cells than R and R-Zn2+ under identical conditions, with the appearance of apoptotic bodies.

Oxovanadium(IV) complexes of curcumin for cellular imaging and mitochondria targeted photocytotoxicity

Oxovanadium(IV) complexes VO(R-tpy)(cur)](ClO4) (1, 2) of curcumin (Hcur) and terpyridine ligands (R-tpy) where R is phenyl (phtpy in 1) or p-triphenylphosphonium methylphenyl bromide (C6H4CH2PPh3Br) (TPP-phtpy in 2) were prepared and characterized and their DNA photocleavage activity, photocytotoxicity and cellular localization in cancer cells (HeLa and MCF-7) were studied. Acetylacetonate (acac) complexes VO(R-tpy)(acac)](ClO4) of phtpy (3) and TPP-phtpy (4) were prepared and used as the control species. These complexes showed efficient cleavage of pUC19 DNA in visible light of 454 nm and near-IR light of 705 rim. Complexes 1 and 2 showed significant photocytotoxicity in visible light of 400-700 nm. FACS analysis showed sub-G1/G0 phase cell-cycle arrest in cancer cells when treated with 1 and 2 in visible light in comparison with the dark controls. Fluorescence microscopic studies revealed specific localization of the p-triphenylphosphonium complex 2 in the mitochondria of MCF-7 cancer cells whereas no such specificity was observed for complex 1.

Oxovanadium(IV) catecholates of terpyridine bases for cellular imaging and photocytotoxicity in red light

Oxovanadium(IV) catecholates of terpyridyl bases, viz. VO(cat)(L)] (L - phtpy, 1; stpy, 2) and VO(dopa-NBD)(L)] (L = phtpy, 3; stpy, 4), where cat is benzene-1,2-diolate, dopa-NBD is 4-(2-(4-nitrobenzoc]1,2,5]oxadiazol-7-ylamino)ethyl)benzene-1,2-di olate, phtpy is (4'-phenyl)-2,2':6',2 `'-terpyridine and stpy is (2,2':6',2 `'-terpyridin-4'-oxy)ethyl-beta-D-glucopyranoside, were prepared and characterized, and their DNA binding, DNA photo-cleavage activity, photocytotoxicity in red light (600-720 nm), cellular uptake and intracellular localization behaviour were studied. The complexes showed an intense ligand-to-metal charge transfer (LMCT) band at similar to 500 nm. The sugar appended complexes 2 and 4 showed significant uptake into the cancer cells. The dopa-NBD complexes 3 and 4 showing green emission were used for cellular imaging. The complexes showed diffused cellular localization mainly in the cytosol and to a lesser extent into the nucleus as evidenced from the confocal microscopy study. Complexes 1-4 showed significant photocytotoxicity in the PDT spectral window giving low IC50 values, while remaining relatively non-toxic in dark.

Comparative Studies on the Bioremediation of Hexavalent and Trivalent Chromium using Citrobacter freundii: Part I-Effect of parameters controlling Biosorption

The potential of Citrobacter freundii, a Gram negative bacteria for the remediation of hexavalent chromium (Cr(VI)) and trivalent chromium (Cr(III))) from aqueous solutions was investigated. Bioremediation of Cr(VI) involved both biosorption and bioreduction processes, as compared to only biosorption process observed with respect to Cr(III) bioremediation. In the case of Cr(VI) bioremediation studies, about 59 % biosorption was achieved at an equilibrium time of 2 h, initial Cr(VI) concentration of 4 mg/L, pH 1 and a biomass loading of 5x10(11) cells/mL. The remainder, 41 %, was found to be in the form of Cr(111) ions owing to bioreduction of Cr(VI) by the bacteria resulting in the absence of Cr(VI) ions in the residue, there by meeting the USEPA specifications. Similar studies were carried out using Cr(III) solution for an equilibrium time of 2 h, Cr(III) concentration of 4 mg/L, pH 3 and a biomass loading of 6.3x10(11) cells/mL., wherein a maximum biosorption of about 30 % was achieved.

Room temperature ferromagnetic and ferroelectric properties of Bi1-xCaxMnO3 thin films

Bi1-xCaxMnO3 (BCMO) thin films with x = 0, 0.1, 0.2, 0.3 and 0.4 are successfully deposited on the n-type Si (100) substrate at two different temperatures of 400 degrees C and 800 degrees C using RF magnetron sputtering. The stoichiometry of the films and oxidation state of the elements have been described by X-ray photoelectron spectroscopy analysis. Dielectric measurement depicts the insulating property of BCMO films. Magnetic and ferroelectric studies confirm the significant enhancement in spin orientation as well as electric polarization at room temperature due to incorporation of Ca2+ ions into BiMnO3 films. The BCMO (x = 0.2) film grown at 400 degrees C shows better magnetization (M-sat) and polarization (P-s) with the measured values of 869 emu / cc and 6.6 mu(C)/cm(2) respectively than the values of the other prepared films. Thus the realization of room temperature ferromagnetic and ferroelectric ordering in Ca2+ ions substituted BMO films makes potentially interesting for spintronic device applications. (C) 2014 Author(s).

Seleno-Nucleobases and Their Water-Soluble Ruthenium-Arene Half-Sandwich Complexes: Chemistry and Biological Activity

Half-sandwich organometallic ruthenium complexes of seleno-nucleobases, 3 and 4, were synthesized and characterized. The structures of both complexes were determined by X-ray crystallography and are the first crystal structures of ruthenium complexes with seleno-nucleobases. Interestingly, 3 self-assembles aided by adventitious water in DMF to give a tetranuclear square 3a center dot 6H(2)O. Complex 4 is active against Jurkat and Molt-4 cell lines but inactive against the K562 cell line, whereas 3 is completely inactive against all three cell lines. The free ligand 6-selenopurine (1) and 6-selenoguanine (2) are highly active against these cell lines. Compound 2, like its thio analogue, is unstable under UVA light, whereas 4 is stable under similar conditions, which suggests that the ruthenium complex could reduce problems associated with the instability of the free ligand, 2, under irradiation.

Study the effect of electrical and mechanical shock loading on liberation and milling characteristics of mineral materials

Milling is an energy intensive process and it is considered as one of the most energy inefficient processes. Electrical and mechanical shock loading can be used to develop a pre-treatment methodology to enhance energy efficiency of comminution and liberation of minerals. Coal and Banded Hematite Jasper (BHJ) Iron ores samples were taken for the study to know the effect of shock loading. These samples were exposed to 5 electric shocks of 300 kV using an electric shock loading device. A diaphragmless shock tube was used to produce 3 and 6 compressed air shocks of Mach number 2.12 to treat the coal and Iron ore samples. Microscopic, comminution and liberation studies were carried out to compare the effectiveness of these approaches. It was found that electric shock loading can comminute the coal samples more effectively and increases the yield of carbon by 40% at 1.6 gm/cc density over the untreated coal samples. Mechanical shock loading showed improved milling performance for both the materials and 12.90% and 8.1% reduction in the D-80 of the particles was observed during grinding for treated samples of coal and iron, respectively. Liberation of minerals in BHJ Iron ore was found unaffected due to low intensity of the mechanical shock waves and non conductivity of minerals. Compressed air based shock loading is easier to operate than electrical shock loading and it needs to be explored further to improve the energy efficacy of comminution. (C) 2014 Elsevier Ltd. All rights reserved.

2-(Phenylazo)pyridineplatinum(II) Catecholates Showing Photocytotoxicity, Nuclear Uptake, and Glutathione-Triggered Ligand Release

Platinum(II) complexes Pt(pap)(an-cat)] (1) and Pt(pap)(py-cat)] (2) with 2-(phenylazo)pyridine (pap), 4-2-(anthracen-9-ylmethylene)amino]ethyl]benzene-1,2-diol (H(2)an-cat), and 4-2-(pyren-1-ylmethylene)amino]ethyl]benzene-1,2-diol (H2py-cat) were prepared, and their photoinduced cytotoxicity was studied. The complexes were found to release catecholate ligand in the presence of excess glutathione (GSH), resulting in cellular toxicity in the cancer cells. The catecholate complex Pt(pap)(cat)] (3) was prepared and used as a control. Complex 3, which is structurally characterized by X-ray crystallography, has platinum(II) in a distorted square-planar geometry. The complexes are redox-active, showing responses near 0.6 and 1.0 V versus SCE in N,N-dimethylformamide/0.1 M tetrabutylammonium perchlorate corresponding to a two-step catechol oxidation process and at -0.3 and -1.3 V for reduction of the pap ligand. Complex 1 showed remarkable light-induced cytotoxicity in HaCaT (human skin keratinocytes) and MCF-7 (human breast cancer) cells, giving IC50 value of similar to 5 mu M in visible light of 400-700 nm and >40 mu M in the dark. The 2',7'-dichlorofluorescein diacetate (DCFDA) assay showed the generation of reactive oxygen species (ROS), which seems to trigger apoptosis, as is evident from the annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) assay. The fluorescence microscopic images showed significant nuclear localization of the complexes and free ligands. A mechanistic study revealed possible reduction of the coordinated azo bond of pap by cellular GSH, releasing the catecholate ligand and resulting in remarkable photochemotherapeutic action of the complexes.

Genome-wide methylation profiling identifies an essential role of reactive oxygen species in pediatric glioblastoma multiforme and validates a methylome specific for H3 histone family 3A with absence of G-CIMP/isocitrate dehydrogenase 1 mutation

Background. Pediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH) 1 mutation with a DNA methylation signature. The present study aims to validate these findings in an independent cohort of pediatric GBM, compare it with adult GBM, and evaluate the involvement of important functionally altered pathways. Methods. Genome-wide methylation profiling of 21 pediatric GBM cases was done and compared with adult GBM data (GSE22867). We performed gene mutation analysis of IDH1 and H3 histone family 3A (H3F3A), status evaluation of glioma cytosine-phosphate-guanine island methylator phenotype (G-CIMP), and Gene Ontology analysis. Experimental evaluation of reactive oxygen species (ROS) association was also done. Results. Distinct differences were noted between methylomes of pediatric and adult GBM. Pediatric GBM was characterized by 94 hypermethylated and 1206 hypomethylated cytosine-phosphate-guanine (CpG) islands, with 3 distinct clusters, having a trend to prognostic correlation. Interestingly, none of the pediatric GBM cases showed G-CIMP/IDH1 mutation. Gene Ontology analysis identified ROS association in pediatric GBM, which was experimentally validated. H3F3A mutants (36.4%; all K27M) harbored distinct methylomes and showed enrichment of processes related to neuronal development, differentiation, and cell-fate commitment. Conclusions. Our study confirms that pediatric GBM has a distinct methylome compared with that of adults. Presence of distinct clusters and an H3F3A mutation-specific methylome indicate existence of epigenetic subgroups within pediatric GBM. Absence of IDH1/G-CIMP status further indicates that findings in adult GBM cannot be simply extrapolated to pediatric GBM and that there is a strong need for identification of separate prognostic markers. A possible role of ROS in pediatric GBM pathogenesis is demonstrated for the first time and needs further evaluation.

Chemical Functionalization of Graphene To Augment Stem Cell Osteogenesis and Inhibit Biofilm Formation on Polymer Composites for Orthopedic Applications

Toward designing the next generation of resorbable biomaterials for orthopedic applications, we studied poly(epsilon-caprolactone) (PCL) composites containing graphene. The role, if any, of the functionalization of graphene on mechanical properties, stem cell response, and biofilm formation was systematically evaluated. PCL composites of graphene oxide (GO), reduced GO (RGO), and amine-functionalized GO (AGO) were prepared at different filler contents (1%, 3%, and 5%). Although the addition of the nanoparticles to PCL markedly increased the storage modulus, this increase was largest for GO followed by AGO and RGO. In vitro cell studies revealed that the AGO and GO particles significantly increased human mesenchymal stem cell proliferation. AGO was most effective in augmenting stem cell osteogenesis leading to mineralization. Bacterial studies revealed that interaction with functionalized GO induced bacterial cell death because of membrane damage, which was further accentuated by amine groups in AGO. As a result, AGO composites were best at inhibiting biofilm formation. The synergistic effect of oxygen containing functional groups and amine groups on AGO imparts the optimal combination of improved modulus, favorable stem cell response, and biofilm inhibition in AGO-reinforced composites desired for orthopedic applications. This work elucidates the importance of chemical functionalization of graphene in polymer composites for biomedical applications.

Remarkable visible light-triggered cytotoxicity of mitochondria targeting mixed-ligand cobalt(III) complexes of curcumin and phenanthroline bases binding to human serum albumin

Six new mixed-ligand cobalt(III) complexes of formulation Co(N-N)(2)(O-O)](ClO4)(2) (1-6), where N-N is a N,N-donor phenanthroline base, namely, 1,10-phenanthroline (phen in 1, 2), dipyrido3,2-d:2',3'-f] quinoxaline (dpq in 3, 4), and dipyrido3,2-a:2',3'-c]phenazine (dppz in 5, 6), O-O is acetylacetonate (acac in 1, 3, 5) or curcumin (bis(4-hydroxy-3-methoxyphenyl)-1,6-diene-3,5-dione, cur in 2, 4, 6), have been synthesized and characterized. The X-ray crystal structures of complex 1 (as PF6- salt, 1a) and 3 show distorted octahedral geometries formed by the CoN4O2 core. The complexes 1, 3 and 5 having the simple acac ligand are prepared as control species to understand the role of curcumin. The optimized geometries and the frontier orbitals of the curcumin complexes 2, 4, and 6 are obtained from the DFT calculations. The complexes 2, 4, and 6 having the photoactive curcumin moiety display an absorption band in the visible region near 420 nm and show remarkable photocytotoxicity in HeLa cancer cells with respective IC50 values of 7.4 mu M, 5.1 mu M and 1.6 mu M while being much less toxic in dark. MTT assay using complex 6 shows that it is not significantly photocytotoxic to MCF-10A normal cells. The control complexes having the acac ligand are non-toxic both in the presence and absence of light. The cell death is apoptotic in nature and triggered by the photogeneration of reactive oxygen species. Fluorescence imaging experiments on HeLa cells reveals that complex 6 accumulated primarily inside the mitochondria. Human serum albumin (HSA) binding experiments show that the complexes bind HSA with good affinity, but 6 binds with the highest affinity, with a K-b value of 9.8 x 10(5) M-1. Thus, complex 6 with its negligible toxicity in the dark and in normal cells but remarkable toxicity in visible light holds significant photochemotherapeutic potential.

CHARACTERIZATION AND MICROHARDNESS OF ELECTRODEPOSITED Ni-W COATINGS OBTAINED FROM GLUCONATE BATH

Ni-W alloy coatings are electrodeposited with direct and pulse current using gluconate bath at pH5. Effects of direct current (DC) and pulse current (PC) on structural characteristics of the coatings have been investigated by energy dispersive X-ray spectroscopy (EDXS), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC) and X-ray photoelectron spectroscopy (XPS). EDXS shows that W contents are 13.3 and 12.6 at.% in DC and PC (10:40) Ni-W coatings, respectively. FESEM analysis exhibits the homogeneous coarse nodular morphology in DC plated deposits. DSC studies reveal that Ni-W coatings are thermally stable up to 400 degrees C. XPS studies demonstrate that DC plated coating has significant amount of Ni and W in elemental form along with their respective oxidized species. In contrast, mainly oxidized metals are present in the as-deposited coatings prepared with PC plating. The microhardness of pulse current (100:400) deposited Ni-W coating is about 750HK that is much higher than DC plated coating (635 HK). Heat treatment of the deposits carried out at different temperatures show a significant increase in microhardness which can be comparable with hard chromium coatings.

Photocytotoxic oxovanadium(IV) complexes of ferrocenyl-terpyridine and acetylacetonate derivatives

Oxovanadium(IV) complexes VO(Fc-tpy)(acac)](ClO4) (1), VO(Fc-tpy)(nap-acac)](ClO4) (2), VO(Fc-tpy)(py-acac)](ClO4) (3) and VO(Ph-tpy)(py-acac)](ClO4) (4) of 4'-ferroceny1-2,2':6',2 `'-terpyridine (Fc-tpy) and 4'-phenyl-2,2':6',2 `'-terpyridine (Ph-tpy) having monoanionic acetylacetonate (acac), naphthylacetylacetonate (nap-acac) or pyrenylacetylacetonate (py-acac) ligand were prepared, characterized and their photocytotoxicity in visible light studied. The ferrocenyl complexes 1-3 showed an intense charge transfer band near 585 nm in DMF and displayed Fc(+)/Fc and V(IV)/V(III) redox couples near 0.66 V and -0.95 V vs. SCE in DMF-0.1 M TBAP. The complexes as avid binders to calf thymus DNA showed significant photocleavage of plasmid DNA in green light (568 nm) forming center dot OH radicals. The complexes that are photocytotoxic in HeLa and MCF-7 cancer cells in visible light (400-700 nm) with low dark toxicity remain nontoxic in normal fibroblast 3T3 cells. ICP-MS and fluorescence microscopic studies show significant cellular uptake of the complexes. Photo-irradiation of the complexes causes apoptotic cell death by ROS as evidenced from the DCFDA assay. (C) 2015 Elsevier Masson SAS. All rights reserved.

Synthesis, X-ray structure and in vitro cytotoxicity studies of Cu(I/II) complexes of thiosemicarbazone: special emphasis on their interactions with DNA

4-(p-X-phenyl)thiosemicarbazone of napthaldehyde {where X = Cl (HL1) and X = Br (HL2)}, thiosemicarbazone of quinoline-2-carbaldehyde (HL3) and 4-(p-fluorophenyl) thiosemicarbazone of salicylaldehyde (H2L4) and their copper(I) {Cu(HL1)(PPh3)(2)Br]center dot CH3CN (1) and Cu(HL2)(PPh3)(2)Cl]center dot DMSO (2)} and copper(II) {((Cu2L2Cl)-Cl-3)(2)(mu-Cl)(2)]center dot 2H(2)O (3) and Cu(L-4)(Py)] (4)} complexes are reported herein. The synthesized ligands and their copper complexes were successfully characterized by elemental analysis, cyclic voltammetry, NMR, ESI-MS, IR and UV-Vis spectroscopy. Molecular structures of all the Cu(I) and Cu(II) complexes have been determined by X-ray crystallography. All the complexes (1-4) were tested for their ability to exhibit DNA-binding and - cleavage activity. The complexes effectively interact with CT-DNA possibly by groove binding mode, with binding constants ranging from 10(4) to 10(5) M-1. Among the complexes, 3 shows the highest chemical (60%) as well as photo-induced (80%) DNA cleavage activity against pUC19 DNA. Finally, the in vitro antiproliferative activity of all the complexes was assayed against the HeLa cell line. Some of the complexes have proved to be as active as the clinical referred drugs, and the greater potency of 3 may be correlated with its aqueous solubility and the presence of the quinonoidal group in the thiosemicarbazone ligand coordinated to the metal.

Synthesis of cadmium oxide and carbon nanotube based nanocomposites and their use as a sensing interface for xanthine detection

Xanthine oxidase (XOD) extracted from bovine milk was immobilized covalently via N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxy succinimide (NHS) chemistry onto cadmium oxide nanoparticles (CdO)/carboxylated multiwalled carbon nanotube (c-MWCNT) composite film electrodeposited on the surface of an Au electrode. The nanocomposite modified Au electrode was characterized by Fourier transform infrared (FTIR), cyclic voltammetry (CV), scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS) before and after immobilization of XOD. Under optimal operation conditions (25 degrees C, + 0.2 V vs. Ag/AgCl, sodium phosphate buffer, pH 7.5), the following characteristics are attributed to the biosensor: linearity of response up to xanthine concentrations of 120 mu M, detection limit of 0.05 mu M (S/N = 3) and a response time of at most 4 s. After being used 100 times over a period of 120 days, only 50% loss of the initial activity of the biosensor was evaluated when stored at 4 degrees C. The fabricated biosensor was successfully employed for the determination of xanthine in fish meat.