Ferrocenyl-L-amino acid copper(II) complexes showing remarkable photo-induced anticancer activity in visible light

Ferrocene-conjugated copper(II) complexes Cu(Fc-aa)(aip)](ClO4) (1-3) and (Cu(Fc-aa)(pyip)](ClO4) (4-6) of L-amino acid reduced Schiff bases (Fc-aa), 2-(9-anthryl)-1H-imidazo4,5-f]1,10]phenanthroline (aip) and 2-(1-pyrenyl)-1H-imidazo4,5-f] 1,10]phenanthroline (pyip), where Fc-aa is ferrocenylmethyl-L-tyrosine (Fc-Tyr in 1, 4), ferrocenylmethyl-L-tryptophan (Fc-Trp in 2, 5) and ferrocenylmethyl-L-methionine (Fc-Met in 3, 6), were prepared and characterized, and their photocytotoxicity was studied (Fc = ferrocenyl moiety). Phenyl analogues, viz. (Cu(Ph-Met)(aip)](ClO4) (7) and (Cu(Ph-Met)(pyip)](ClO4) (8), were prepared and used as control compounds. The bis-imidazophenanthroline copper(II) complexes, viz. (Cu(aip)(2)(NO3)](NO3) (9) and Cu(pyip)(2)(NO3)](NO3) (10), were also prepared and used as controls. Complexes 1-6 having a redox inactive cooper(II) center showed the Fc(+)-Fc redox couple at similar to 0.5 V vs. SCE in DMF-0.1 mol (Bu4N)-N-n](ClO4). The copper(II)-based d-d band was observed near 600 nm in DMF-Tris-HCl buffer (1 :1 v/v). The ferrocenyl complexes showed low dark toxicity, but remarkably high photocytotoxicity in human cervical HeLa and human breast adenocarcinoma MCF-7 cancer cells giving an excellent photo-dynamic effect while their phenyl analogues were inactive. The photo-exposure caused significant morphological changes in the cancer cells when compared to the non-irradiated ones. The photophysical processes were rationalized from the theoretical studies. Fluorescence microscopic images showed 3 and 6 localizing predominantly in the endoplasmic reticulum (ER) of the cancer cells, thus minimizing any undesirable effects involving nuclear DNA.

A Probe for the Selective and Parts-per-Billion-Level Detection of Copper(II) and Mercury(II) using a Micellar Medium and Its Utility in Cell Imaging

A novel colorimetric probe 1 based on the picolyl moiety has been designed and synthesized. Probe 1 is composed of a pyrene and a bispicolyl amine (BPA) unit, in which the BPA moiety acts as a binding unit and the binding phenomenon is sensed from the changes in the signaling subunit. The probe detects Cu2+ specifically in water and both Cu2+ and Hg2+ efficiently in neutral Brij-58 micellar media. The probe shows a color change visible to the naked eye upon addition of metal ions. Notably, in a micellar medium, probe 1 can detect both the Cu2+ and Hg2+ ions even at parts-per-billion levels. Furthermore, the probe shows ratiometric detection of both the metal ions making the sensing quantitative. The two metal ions could be discriminated both visibly under a UV lamp and with the use of fluorescence spectroscopy. The probe could be also used in biological cell lines for the detection of both Hg2+ and Cu2+ ions.

Copper-Catalyzed Decarboxylative Sulfonylation of alpha,beta-Unsaturated Carboxylic Acids

Copper-catalyzed, ligand-promoted decarboxylative coupling of readily available a,fi-unsaturated acids with sodium aryl sulfinates is presented. This method provides a new avenue for the synthesis of vinyl sulfones via a decarboxylative radical coupling strategy by employing a catalytic amount of Cu(ClO4)(2)center dot 6H(2)O, TBHP in decane as an oxidant, and 1,10-phenanthroline as a ligand. The salient feature of this method is that it furnishes exclusively the (E)-isomer.

Simultaneous co-ordination of three cytosine ligands displaying different binding sites around the copper centres

We report the synthesis and structural characterization of a polymeric ternary copper-cytosine-phenanthroline complex, Cu-4(phen)(3)-(mu(3)-cyt)(2)(mu-OH)(cyt)(OH)Cl-3](n)center dot 16H(2)O, where three cytosine ligands with different binding sites have simultaneously complexed to the four copper metal centres. Interestingly, the complex exhibits two different coordination geometries around the metal centres.

Phenyl carbohydrazone conjugated 2-oxoindoline as a new scaffold that augments the DNA and BSA binding affinity and anti-proliferative activity of a 1,10-phenanthroline based copper(II) complex

A new type of copper(II) complex, CuL(phen)(2)](NO3) (CuIP), where L ((E)-N'-(2-oxoindolin-3-ylidene) benzohydrazide) is a N donor ligand and phen is the N, N-donor heterocyclic 1,10-phenanthroline, has been synthesized. The phenyl carbohydrazone conjugated isatin-based ligand L and CuIP were characterized by elemental analysis, infrared, UV-Vis, H-1 and C-13 NMR and ESI-mass spectral data, as well as single-crystal X-ray diffraction. The interaction of calf thymus DNA (CT DNA) with L and CuIP has been investigated by absorption, fluorescence and viscosity titration methods. The complex CuIP displays better binding affinity than the ligand L. The observed DNA binding constant (K-b = 4.15(+/- 0.18) x 10(5) M-1) and binding site size (s = 0.19), viscosity data together with molecular docking studies of CuIP suggest groove binding and/or a partial intercalative mode of binding to CT DNA. In addition, CuIP shows good binding propensity to the bovine serum albumin (BSA) protein, giving a K-BSA value of 1.25(+/- 0.24) x 10(6) M-1. In addition, the docking studies on DNA and human serum albumin (HSA) CuIP interactions are consistent with the consequence of binding experiments. The in vitro anti-proliferative study establishes the anticancer potency of the CuIP against the human cervical (HeLa) and breast (MCF7) cancer cells; noncancer breast epithelial (MCF10a) cells have also been investigated. CuIP shows better cytotoxicity and sensitivity towards cancer cells over noncancer ones than L under identical conditions, with the appearance of apoptotic bodies. (C) 2014 Elsevier B.V. All rights reserved.

Synthesis and crystal structure of copper (II) uracil ternary polymeric complex with 1,10-phenanthroline along with the Hirshfeld surface analysis of the metal binding sites for the uracil ligand

The study of models for ``metal-enzyme-substrate'' interaction has been a proactive area of research owing to its biological and pharmacological importance. In this regard the ternary copper uracil complex with 1,10-phenanthroline represents metal-enzyme-substrate system for DNA binding enzymes. The synthesis of the complex, followed by slow evaporation of the reaction mixture forms two concomitant solvatomorph crystals viz., {Cu(phen)(mu-ura)(H2O)](n)center dot H2O (1a)} and {Cu(phen)(mu-ura)(H2O)](n)center dot CH3OH (1b)}. Both complexes are structurally characterized, while elemental analysis, IR and EPR spectra were recorded for 1b (major product). In both complexes, uracil coordinates uniquely via N1 and N3 nitrogen atom acting as a bidentate bridging ligand forming a 1-D polymer. The two solvatomorphs were quantitatively analyzed for the differences with the aid of Hirshfeld surface analysis. (C) 2014 Elsevier B.V. All rights reserved.

Synthesis, crystal structure and spectroscopic and electrochemical properties of bridged trisbenzoato copper-zinc heterobinuclear complex of 2,2 `-bipyridine

The synthesis of the heterobinuclear copper-zinc complex CuZn(bz)(3)(bpy)(2)]ClO4 (bz = benzoate) from benzoic acid and bipyridine is described. Single crystal X-ray diffraction studies of the heterobinuclear complex reveals the geometry of the benzoato bridged Cu(II)-Zn(II) centre. The copper or zinc atom is pentacoordinate, with two oxygen atoms from bridging benzoato groups and two nitrogen atoms from one bipyridine forming an approximate plane and a bridging oxygen atom from a monodentate benzoate group. The Cu-Zn distance is 3.345 angstrom. The complex is normal paramagnetic having mu(eff) value equal to 1.75 BM, ruling out the possibility of Cu-Cu interaction in the structural unit. The ESR spectrum of the complex in CH3CN at RT exhibit an isotropic four line spectrum centred at g = 2.142 and hyperfine coupling constants A(av) = 63 x 10(-4) cm(-1), characteristic of a mononuclear square-pyramidal copper(II) complexes. At LNT, the complex shows an isotropic spectrum with g(parallel to) = 2.254 and g(perpendicular to) =2.071 and A(parallel to) = 160 x 10(-4) cm(-1). The Hamiltonian parameters are characteristic of distorted square pyramidal geometry. Cyclic voltammetric studies of the complex have indicated quasi-reversible behaviour in acetonitrile solution. (C) 2014 Elsevier B.V. All rights reserved.

Insights on Defect-Mediated Heterogeneous Nucleation of Graphene on Copper

The grain size of monolayer large area graphene is key to its performance. Microstructural design for the desired grain size requires a fundamental understanding of graphene nucleation and growth. The two levers that can be used to control these aspects are the defect density, whose population can be controlled by annealing, and the gas-phase supersaturation for activation of nucleation at the defect sites. We observe that defects on copper surface, namely dislocations, grain boundaries, triple points, and rolling marks, initiate nucleation of graphene. We show that among these defects dislocations are the most potent nucleation sites, as they get activated at lowest supersaturation. As an illustration, we tailor the defect density and supersaturation to change the domain size of graphene from <1 mu m(2) to >100 mu m(2). Growth data reported in the literature has been summarized on a supersaturation plot, and a regime for defect-dominated growth has been identified. In this growth regime, we demonstrate the spatial control over nucleation at intentionally introduced defects, paving the way for patterned growth of graphene. Our results provide a unified framework for understanding the role of defects in graphene nucleation and can be used as a guideline for controlled growth of graphene.

Low-Wear High-Friction Behavior of Copper Matrix Composites Dispersed With an In Situ Polymer Derived Ceramic

We show that copper-matrix composites that contain 20 vol. % of an in situ processed, polymer-derived, ceramic phase constituted from Si-C-N have unusual friction-and-wear properties. They show negligible wear despite a coefficient of friction (COF) that approaches 0.7. This behavior is ascribed to the lamellar structure of the composite such that the interlamellar regions are infused with nanoscale dispersion of ceramic particles. There is significant hardening of the composite just adjacent to the wear surface by severe plastic deformation.

Effect of grain boundary engineering on the microstructure and mechanical properties of copper containing austenitic stainless steel

The present investigation deals with grain boundary engineering of a modified austenitic stainless steel to obtain a material with enhanced properties. Three types of processing that are generally in agreement with the principles of grain boundary engineering were carried out. The parameters for each of the processing routes were fine-tuned and optimized. The as-processed samples were characterized for microstructure and texture. The influence of processing on properties was estimated by evaluating the room temperature mechanical properties through micro-tensile tests. It was possible to obtain remarkably high fractions of CSL boundaries in certain samples. The results of the micro-tensile tests indicate that the grain boundary engineered samples exhibited higher ductility than the conventionally processed samples. The investigation provides a detailed account of the approach to be adopted for GBE processing of this grade of steel. (C) 2014 Elsevier B.V. All rights reserved.

Effect of Micro-Structured Copper as Cathode Material for P3HT-Based Diode

Here, the effect of micro-structured cathode material on the device performance of indium tin oxide/poly(3hexylethiophene)/copper diode (ITO/P3HT/Cu) is investigated. Two different forms of copper namely bulk metal (Cu{B}) and nanoparticle (Cu{N}) were used as top electrode to probe its effect on device performance. Crystallographic structure and nanoscale morphology of top Cu electrodes were characterized using X-ray diffraction and scanning electronmicroscopy. Electrode formed by evaporation of copper nanoparticle showed enhancement in current density. From capacitance based spectroscopy we observed that density of trap states in ITO/P3HT/copper larger size grain (Cu-LG) are one order greater than that in ITO/P3HT/copper smaller size grain (Cu-SG) device.

Postsynthetic Exterior Decoration of an Organic Cage by Copper(I)-Catalysed A(3)-Coupling and Detection of Nitroaromatics

A new synthetic protocol based on one-pot, copper(I)-catalysed multicomponent reaction of formaldehyde, secondary amine and terminal alkyne has been employed to postsynthetically modify a self-assembled nanoscopic organic cage. By employing this synthetic strategy, three new cages appended with phenyl-, xylyl-and naphthyl-acetylene moieties have been synthesised. The resulting modified cages were characterised by using a range of spectroscopic techniques. The synthesised cages were fluorescent and thus one of them was tested to explore the potential use of such compounds as chemosensors for the detection of nitroaromatics. Experimental findings suggest a high selective quenching of initial fluorescence intensity in the presence of nitroaromatic compounds. Furthermore, it has been observed that among the various nitroaromatics tested, nitrophenolic compounds have better quenching ability.

Copper-Catalyzed Direct Transformation of Secondary Allylic and Benzylic Alcohols into Azides and Amides: An Efficient Utility of Azide as a Nitrogen Source

A mild and convenient method for the synthesis of amides has been explored by using secondary alcohols, Cu(ClO4)(2)6H(2)O as a catalyst, and trimethylsilyl azide (TMSN3) as a nitrogen source in the presence of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) at ambient temperature. This method has been successfully adapted to the preparation of azides directly from their corresponding alcohols and offers excellent chemoselectivity in the formation of -halo azides and the azidation of allylic alcohols in the presence of a benzyl alcohol moiety. In addition, this strategy provides an opportunity to synthesize azides that can serve as precursors to -amino acids.

Synthesis and characterization of monometallic rhenium(I) complexes and their application as selective sensors for copper(II) ions

Novel imine functionalized monometallic rhenium(I) polypyridine complexes (1-4) comprising two phenol moieties attached to 2,20-bipyridine ligands L1-L4 have been synthesized and characterized. These complexes exhibit selective and sensitive detection towards copper(II) ions and this is observed through changes in UV-visible absorption, luminescence and time-resolved spectroscopic techniques. An enormous enhancement is observed in emission intensity, quantum yield and luminescence lifetime with the addition of copper(II) ions, and this can be attributed to the restriction of C=N isomerization in the Re(I) complexes. The strong binding between copper(II) ions and these complexes reveals that the binding constant values are in the range of 1.1 x 10(3)-6.0 x 103 M-1. The absorption spectral behavior of the complexes is supported by DFT calculations.

BODIPY appended copper(II) complexes of curcumin showing mitochondria targeted remarkable photocytotoxicity in visible light

Copper(II) complexes of BODIPY (borondipyrromethene) derivatives (L-1, L-2) and curcumin (Hcur), viz. Cu(L-1)(cur)]Cl (1) and Cu(L-2)(cur)]Cl (2), where L-1 and L-2 are the non-iodinated and diiodinated BODIPY appended dipicolylamine ligands, are prepared and characterized and their photocytotoxic activity in visible light studied. Binding to copper(II) has rendered stability to curcumin from its hydrolytic degradation in buffer medium. The complexes show mitochondrial localization in HeLa cells emphasizing the findings that both 1 and 2 are mitochondria-targeting complexes and induce cancer cell death. Complex 1 with a fluorophoric BODIPY moiety in L-1 gave IC50 values of 7.9(+/- 0.3) mu M in visible light (400-700 nm) and 29.1(+/- 0.5) mu M in the dark. Complex 2 having a diiodo BODIPY moiety in L-2 as a photosensitizer gave IC50 values of 3.8(+/- 0.2) mu M in visible light and 32.1(+/- 0.4) mu M in the dark. The PDT effect of 2 is comparable to that of Photofrin (R), an FDA approved PDT drug. Cell death follows an apoptotic pathway with the formation of reactive oxygen species (ROS).