Impact of metal binding on the antitumor activity and cellular imaging of a metal chelator cationic imidazopyridine derivative

A new water soluble cationic imidazopyridine species, viz. (1E)-1-((pyridin-2-yl)methyleneamino)-3-(3-(pyridin-2-yl)imidazo[1,5-a]pyridin-2(3H)-yl)propan-2-ol (1), as a metal chelator is prepared as its PF(6) salt and characterized. Compound 1 shows fluorescence at 438 nm on excitation at 342 nm in Tris-HCl buffer giving a fluorescence quantum yield (φ) of 0.105 and a life-time of 5.4 ns. Compound 1, as an avid DNA minor groove binder, shows pUC19 DNA cleavage activity in UV-A light of 365 nm forming singlet oxygen species in a type-II pathway. The photonuclease potential of 1 gets enhanced in the presence of Fe(2+), Cu(2+) or Zn(2+). Compound 1 itself displays anticancer activity in HeLa, HepG2 and Jurkat cells with an enhancement on addition of the metal ions. Photodynamic effect of 1 at 365 nm also gets enhanced in the presence of Fe(2+) and Zn(2+). Fluorescence-based cell cycle analysis shows a significant dead cell population in the sub-G1 phase of the cell cycle suggesting apoptosis via ROS generation. A significant change in the nuclear morphology is observed from Hoechst 33258 and an acridine orange/ethidium bromide (AO/EB) dual nuclear staining suggesting apoptosis in cells when treated with 1 alone or in the presence of the metal ions. Apoptosis is found to be caspase-dependent. Fluorescence imaging to monitor the distribution of 1 in cells shows that 1 in the presence of metal ions accumulates predominantly in the cytoplasm. Enhanced uptake of 1 into the cells within 12 h is observed in the presence of Fe(2+) and Zn(2+).     

Ferrocene-conjugated L-tryptophan copper(II) complexes of phenanthroline bases showing DNA photocleavage activity and cytotoxicity

Ferrocene-conjugated L-tryptophan (L-Trp) reduced Schiff base (Fc-TrpH) copper(II) complexes [Cu(Fc-Trp)(L)](ClO(4)) of phenanthroline bases (L), viz. 2,2'-bipyridine (bpy in 1), 1,10-phenanthroline (phen in 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 3), and dipyrido[3,2-a:2',3'-c]phenazine (dppz in 4), were prepared and characterized and their photocytotoxicity studied. Cationic reduced Schiff base (Ph-TrpH) complexes [Cu(Ph-Trp)(L)(H(2)O)](ClO(4)) (L = phen in 5; dppz in 6) having the ferrocenyl moiety replaced by a phenyl group and the Zn(II) analogue (7) of complex 4 were prepared and used as control species. The crystal structures of 1 and 5 with respective square-planar CuN(3)O and square-pyramidal CuN(3)O(2) coordination geometry show significantly different core structures. Complexes 1-4 exhibit a Cu(II)-Cu(I) redox couple near -0.1 V and the Fc(+)-Fc couple at ~0.5 V vs SCE in DMF-0.1 M [Bu(n)(4)N](ClO(4)) (Fc = ferrocenyl moiety). The complexes display a copper(II)-based d-d band near 600 nm and a Fc-centered band at ~450 nm in DMF-Tris-HCl buffer. The complexes are efficient binders to calf thymus DNA. They are synthetic chemical nucleases in the presence of thiol or H(2)O(2), forming hydroxyl radicals. The photoactive complexes are cleavers of pUC19 DNA in visible light, forming hydroxyl radicals. Complexes 2-6 show photocytotoxicity in HeLa cancer cells, giving IC(50) values of 4.7, 10.2, 1.3, 4.8, and 4.3 μM, respectively, in visible light with the appearance of apoptotic bodies. The complexes also show photocytotoxicity in MCF-7 cancer cells. Nuclear chromatin cleavage has been observed with acridine orange/ethidium bromide (AO/EB) dual staining with complex 4 in visible light. The complexes induce caspase-independent apoptosis in the HeLa cells.     

Total conductivity in Sc-doped LaTiO3 + δ perovskites

A series of Sc-doped lanthanum titanate perovskites, LaTi_(1???x)Sc _x O_3?+?δ with x?=?0, 0.2, 0.25 and 0.3, was prepared by sol-gel method. All compositions were found to exhibit orthorhombic crystal structure. An increase in unit cell volume was observed for composition with x?=?0.2. The oxidation states of La³⁺, Sc³⁺ and Ti³⁺ ions have been established using X-ray photoelectron spectroscopy (XPS). It is observed that an enhancement in total conductivity of LaTiO_3?+?δ perovskite is achieved only at lower doping concentration. A reverse effect is observed for higher dopant concentration.     

Copper(II) complex intercalated graphene oxide nanocomposites as versatile,reusable catalysts for click reaction

In this work, we report the efficient, high stable copper(II) complexes intercalated graphene oxide (GO) used as green catalysts for copper(II) complex mediated click reaction. Copper(II) Bis(2,2′-bipyridine) [Cu^II (bpy)₂] (C1) and Copper(II) Bis(1,10-phenanthroline) [Cu^II (phen)₂] (C2) have synthesized for the intercalation of corresponding nanocomposites with GO, [GO@Cu^II (bpy)₂] (GO-C1) and [GO@Cu^II (phen)₂] (GO-C2). The noncovalent interaction of complexes supported on the surface of the GO nanosheets proves as an evident active site to facilitate the enhanced catalytic activity of copper-catalyzed alkyne azide cycloaddition (Cu^IIAAC) reaction for the isolation of 1,4-disubstituted-1,2,3-triazoles as click products in shorter reaction time with 80%–91% yield (five examples). The X-ray diffraction (XRD) pattern of these composites shows the enhanced interlayers d-spacing range of 1.01–1.12 nm due to the intercalation of copper(II) complexes in between the GO basal planes and characterized by X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FT-IR), Raman, UV, scanning electron microscope (SEM), and thermogravimetric analysis (TGA). The as-prepared nanocomposites were employed for the typical click reactions using the substrates of azide and acetylene. These classes of composite materials can be referred to recyclable, heterogeneous, green catalysts with high atom economy and could also be used for the isolation of click products in biomolecules.     

Study of vacancy defects and their thermal stability in MeV Fe ion irradiated RAFM steel using positron beam Doppler broadening spectroscopy

Indian reduced activation ferritic-martensitic steel was irradiated with 1.1?MeV Fe ions to various doses from 1 to100?dpa at room temperature. The depth profiling of irradiation-induced vacancy-type defects and the defect-recovery under post-irradiation annealing was studied using variable low-energy positron beam Doppler broadening spectroscopy. The influence of irradiation-induced defects on the microstructural properties was studied by glancing incidence x-ray diffraction (GIXRD) and nanoindentation technique. Positron annihilation study showed the signatures of reduced vacancy concentration at the peak damage region due to injected interstitial effect from 30 to 100?dpa and the widening of vacancy-interstitial recombination-rich region towards the end of ion range with the increase in dose. The GIXRD results were analysed by modified Williamson–Hall plot method, and the variation of coherent domain size and micro-strain with irradiation dose was studied. Irradiation-induced hardening was observed in the nanoindentation study. The features observed in the GIXRD and nanoindentation study are correlated with the depth-resolved defect distribution observed in the positron annihilation study.     

On a reduction of the generalized Darboux–Halphen system

The equations for the general Darboux–Halphen system obtained as a reduction of the self-dual Yang–Mills can be transformed to a third-order system which resembles the classical Darboux–Halphen system with a common additive terms. It is shown that the transformed system can be further reduced to a constrained non-autonomous, non-homogeneous dynamical system. This dynamical system becomes homogeneous for the classical Darboux–Halphen case, and was studied in the context of self-dual Einstein's equations for Bianchi IX metrics. A Lax pair and Hamiltonian for this reduced system is derived and the solutions for the system are prescribed in terms of hypergeometric functions.     

Effect of steady-state conditions on self-pulsing characteristics of Yb-doped cw fiber lasers

Fiber laser resonator configurations have been analyzed theoretically on the basis of steady-state rate equations to optimize the laser conversion efficiency. Evolution of the pump- and signal powers and the saturated gain coefficient along the length of the laser medium has been simulated for high- and low-finesse resonators in forward- and backward pumping schemes. The corresponding fiber laser configurations have been setup to verify the results of simulation. Backward pumping configuration in an Yb-doped fiber laser has been found to be the most efficient, and in this configuration a maximum cw output power of 10.75 W in single transverse mode with an optical-to-optical conversion efficiency of 62.5% has been achieved. The laser output spectrum was peaked at 1093 nm with full-width at half-maximum (FWHM) line-width of about 9 nm. In the low-finesse resonator configuration, it has been found that experimental observations differ from theoretical simulation results. In this case, output power from both ends ceases to increase linearly beyond 1.8 W, and starts fluctuating due to the onset of strong random self-pulsing phenomenon. Our investigation shows that a non-uniform steady-state gain along the fiber length facilitates the self-pulsing process.     

Study of nano-scale diffusion in thin films and multilayers

It is shown that x-ray reflectivity and x-ray fluorescence under standing wave conditions can be used to study atomic diffusion with an accuracy of a fraction of a nanometer. Both the techniques can be made isotope selective by making use of nuclear resonance scattering from a Mössbauer active isotope. The techniques have been used to study self-diffusion of Fe in amorphous and nano-crystalline alloys of FeZr and FeN. The observed correlation of the activation energy E with pre-exponent factor D₀ confirms that in amorphous FeZr alloy diffusion takes place via collective motion of a group of atoms. Even in nanocrystalline alloys it is found that atomic diffusion occurs mainly through grain boundaries which are amorphous or highly disordered in nature.