An efficient one-pot synthesis and photoinduced DNA cleavage studies of 2-chloro-3-(5-aryl-4,5-dihydroisoxazol-3-yl)quinolines

4,5-Dihydroisoxazoles continue to attract considerable interest due to their wide spread biological activities. Here, we identify an efficient protocol for the preparation of 4,5-dihydroisoxazoles (2-isaxazolines) (4a-g) from quinolinyl chalcones. The nucleolytic activities of synthesized compounds were investigated by agarose gel electrophoresis. All these compounds were showed the remarkable DNA cleavage activity (concentration dependent) with pUC19 DNA at 365 nm UV light. The DNA cleavage activity was significantly enhanced by the presence of iminyl and carboxy radicals of DIQ. (C) 2012 Elsevier Ltd. All rights reserved.

Design and Synthesis of a Functional Derivative of the Triazinium Cation and Its Rhodium Complex that Shows Photoinduced DNA Cleavage Activity and Photocytotoxicity

The design and synthesis of an intensely blue rhodium(III) complex 3]+ of a new N,N-donor ligand, 8-(quinolin-8-ylamino)pyrido2,1-c]1,2,4]benzotriazin-11-ium, 2]+, which contains a planar pendant triazinium arm, is described. Structural characterization for 3]+ was carried out by using various spectroscopic techniques and single-crystal X-ray crystallography. The organometallic rhodium(III) compound shows a ligand-based reversible reduction at 0.65 V. The electrochemically reduced compound displays a single-line EPR spectrum that signifies the formation of ligand-based free radicals. Compound 3]+ shows a binding propensity to calf thymus DNA to give a Kapp value of 6.05X105 M1. The parent triazinium salt, pyrido2,1-c]1,2,4]benzotriazin-11-ium 1]+ and the ligand salt 2]+ exhibit photoinduced cleavage of DNA in UV-A light, whereas the reference Rh complex 3]+ photocleaves DNA with red light (647.1 nm). The compounds show photonuclease activities under both aerobic and anaerobic conditions. Mechanistic investigations under aerobic conditions with several inhibitors indicate the formation of hydroxyl radicals by means of a photoredox pathway. Under anaerobic conditions, it is believed that a photoinduced oxidation of DNA mechanism is operative. Compound 3]+ exhibits photocytotoxicity in HeLa cervical cancer cells to give IC50 values of (12+/-0.9) mu M in UV-A light at 365 nm and (31.4+/-1.1) mu M in the dark.

Ultrafast photoinduced enhancement of nonlinear optical response in 15-atom gold clusters on indium tin oxide conducting film

We show that the third order optical nonlinearity of 15-atom gold clusters is significantly enhanced when in contact with indium tin oxide (ITO) conducting film. Open and close aperture z-scan experiments together with non-degenerate pump-probe differential transmission experiments were done using 80 fs laser pulses centered at 395 nm and 790 nm on gold clusters encased inside cyclodextrin cavities. We show that two photon absorption coefficient is enhanced by an order of magnitude as compared to that when the clusters are on pristine glass plate. The enhancement for the nonlinear optical refraction coefficient is similar to 3 times. The photo-induced excited state absorption using pump-probe experiments at pump wavelength of 395 nm and probe at 790 nm also show an enhancement by an order of magnitude. These results attributed to the excited state energy transfer in the coupled gold cluster-ITO system are different from the enhancement seen so far in charge donor-acceptor complexes and nanoparticle-conjugate polymer composites.

Mitochondria-Targeted Photoinduced Anticancer Activity of Oxidovanadium( IV) Complexes of Curcumin in Visible Light

Oxidovanadium(IV) complexes VO(py-aebmz)(B)]Cl (1, 2) and VO(napth-py-aebmz)(cur)]Cl 3; py-aebmz = 2-(1H-benzimidazol-2-yl)-N-(pyridin-2-ylmethylene)ethanamine, HB = acetylacetone (Hacac, 1) and curcumin (Hcur, 2), napth-py-aebmz = naphthalimide conjugated to py-aebmz ] have been prepared, characterized and their photoinduced DNA cleavage activities and photocytotoxicities studied. Complexes 1-3 each exhibited an irreversible cyclic voltammetric response of the V-IV/V-III redox couple at around -0.85 V versus SCE in dmf/0.1 M tbap. The complexes showed DNA photocleavage activity in visible light of 454, 530 and 647 nm through hydroxyl radical and singlet oxygen pathways. Fluorescence microscopy data suggest mitochondrial localization of complex 3 bearing a naphthalimide with a two-fold increase in photocytotoxicity in HaCaT cells with an IC50 value of 6.3 M and a three-fold increase in MCF-7 cells with an IC50 of 5.4 M compared with complex 2. Both 2 and 3 were non-toxic in the dark.

Syntheses and structural investigation of some alkali metal ion-mediated (LVO2-)-O-V (L2- = tridentate ONO ligands) species: DNA binding, photoinduced DNA cleavage and cytotoxic activities

Eight alkali metal ion-mediated dioxidovanadium(V), {(VO2L1-6)-O-V} A(H2O)n]proportional to, complexes for A = Li+, Na+, K+ and Cs+, containing tridentate aroylhydrazonate ligands coordinating via ONO donor atoms, are described. All the synthesised ligands and the metal complexes were successfully characterised by elemental analysis, IR, UV-Vis and NMR spectroscopy. X-ray crystallographic investigation of 3, 5-7 shows the presence of distorted NO4 coordination geometries for LVO2- in each case, and varying mu-oxido and/ or mu-aqua bridging with interesting variations correlated with the size of the alkali metal ions: with small Li+, no bridging-O is found but four ion aggregates are found with Na+, chains for K+ and finally, layers for Cs+. Two (5) or three-dimensional (3, 6 and 7) architectures are consolidated by hydrogen bonding. The dioxidovanadium(V) complexes were found to exhibit DNA binding activity due to their interaction with CT-DNA by the groove binding mode, with binding constants ranging from 10(3) to 10(4) M-1. Complexes 1-8 were also tested for DNA nuclease activity against pUC19 plasmid DNA which showed that 6 and 7 had the best DNA binding and photonuclease activity; these results support their good protein binding and cleavage activity with binding constants ranging from 104 to 105 M-1. Finally, the in vitro antiproliferative activity of all complexes was assayed against the HeLa cell line. Some of the complexes (2, 5, 6 and 7) show considerable activity compared to commonly used chemotherapeutic drugs. The variation in cytotoxicity of the complexes is influenced by the various functional groups attached to the aroylhydrazone derivative.

Tuning photoinduced terahertz conductivity in monolayer graphene: Optical-pump terahertz-probe spectroscopy

Optical-pump terahertz-probe differential transmission measurements of as-prepared single layer graphene (AG) (unintentionally hole dopedwith Fermi energy E-F at similar to -180 meV), nitrogen doping compensated graphene (NDG) with E-F similar to -10 meV, and thermally annealed doped graphene (TAG) are examined quantitatively to understand the opposite signs of photoinduced dynamic terahertz conductivity Delta sigma. It is negative for AG and TAG but positive for NDG. We show that the recently proposed mechanism of multiple generations of secondary hot carriers due to Coulomb interaction of photoexcited carriers with the existing carriers together with the intraband scattering can explain the change of photoinduced conductivity sign and its magnitude. We give a quantitative estimate of Delta sigma in terms of controlling parameters-the Fermi energy E-F and momentum relaxation time tau. Furthermore, the cooling of photoexcited carriers is analyzed using a supercollision model which involves a defect mediated collision of the hot carriers with the acoustic phonons, thus giving an estimate of the deformation potential.

Metal Complexes of Curcumin for Cellular Imaging, Targeting, and Photoinduced Anticancer Activity

CONSPECTUS: Curcumin is a polyphenolic species. As an active ingredient of turmeric, it is well-known for its traditional medicinal properties. The therapeutic values include antioxidant, anti-inflammatory, antiseptic, and anticancer activity with the last being primarily due to inhibition of the transcription factor NF-kappa B besides affecting several biological pathways to arrest tumor growth and its progression. Curcumin with all these positive qualities has only remained a potential candidate for cancer treatment over the years without seeing any proper usage because of its hydrolytic instability involving the diketo moiety in a cellular medium and its poor bioavailability. The situation has changed considerably in recent years with the observation that curcumin in monoanionic form could be stabilized on binding to a metal ion. The reports from our group and other groups have shown that curcumin in the metal-bound form retains its therapeutic potential. This has opened up new avenues to develop curcumin-based metal complexes as anticancer agents. Zinc(II) complexes of curcumin are shown to be stable in a cellular medium. They display moderate cytotoxicity against prostate cancer and neuroblastoma cell lines. A similar stabilization and cytotoxic effect is reported for (arene)ruthenium(II) complexes of curcumin against a variety of cell lines. The half-sandwich 1,3,5-triaza-7-phosphatricyclo-3.3.1.1]decane (RAPTA)-type ruthenium(II) complexes of curcumin are shown to be promising cytotoxic agents with low micromolar concentrations for a series of cancer cell lines. In a different approach, cobalt(III) complexes of curcumin are used for its cellular delivery in hypoxic tumor cells using intracellular agents that reduce the metal and release curcumin as a cytotoxin. Utilizing the photophysical and photochemical properties of the curcumin dye, we have designed and synthesized photoactive curcumin metal complexes that are used for cellular imaging by fluorescence microscopy and damaging the cancer cells on photoactivation in visible light while being minimally toxic in darkness. In this Account, we have made an attempt to review the current status of the chemistry of metal curcumin complexes and present results from our recent studies on curcumin complexes showing remarkable in vitro photocytotoxicity. The undesirable dark toxicity of the complexes can be reduced with suitable choice of the metal and the ancillary ligands in a ternary structure. The complexes can be directed to specific subcellular organelles. Selectivity by targeting cancer cells over normal cells can be achieved with suitable ligand design. We expect that this methodology is likely to provide an impetus toward developing curcumin-based photochemotherapeutics for anticancer treatment and cure.

Probing Ultrafast Photoinduced Electron Transfer to TiO2 from CdS Nanocrystals of Varying Crystallographic Phase Content

The photoinduced electron transfer processes in a nanoheterostructured semiconductor assembly are complex and depend on various parameters Of the constituents of the assembly. We present here the ultrafast electron transfer characteristics of an assembly comprised of a Wide band semiconductor, titanium dioxide (TiO2), attached to light-harvesting cadmium sulfide (CdS) nanotrystals of varying crystallographic phase content. Quantitative analysis of Synchrotron high-resolution X-ray. diffraction data of CdS nanocrystals precisely reveals the presence of both wurtzite and zinc blende phases in varying amounts. The,estimated content of crystal phases is observed to be strongly dependent on an important synthesis parameter, viz., the ratio of the two solvents. The biphasit nature of CdS influences directly the shape of the nanocrystal at long reaction times as well as the transfer of the photoexcited electrons from the CdS to TiO2 as obtained from transient absorption spectroscopy. A higher amount of zinc blende Phase is observed to be beneficial for fast electron transfer across the CdS-TiO2 interface. The electron transfer rate constant differs by one order of magnitude between the CdS nanocryStals and varies linearly with the fraction of the phases.

Photoinduced DNA Crosslink Formation by Dichloridooxidovanadium(IV) Complexes of Polypyridyl Bases

Oxidovanadium(IV) complexes VO(pyphen)Cl-2] (1) and VO(pydppz)Cl-2] (2), where pyphen is 2-(2-pyridyl)-1,10-phenanthroline and pydppz is 3-(pyridin-2-yl)dipyrido3,2-a:2,3-c]phenazine, show remarkable photoinduced DNA crosslinking ability and photocytotoxicity. The complexes are non-electrolytes in DMF, 1:1 electrolytes in 20% aqueous DMF, and 1:2 electrolytes in 20% aqueous DMF upon photoirradiation with visible light of 400-700 nm. The paramagnetic complexes, which have one unpaired electron, show a d-d band near 780 nm in aqueous DMF. The IR data suggest a V=O moiety trans to a V-N bond. Complex VO(pydppz)Cl-2] (2), as a novel photoinducible nuclear ds-DNA crosslinking agent, shows visible-light-induced cytotoxicity in HeLa and MCF-7 cancer cells by an apoptotic pathway, giving IC50 values of 0.87 +/- 0.07 and 1.4 +/- 0.2 M, respectively, while being essentially nontoxic (IC50 > 40 M) in the dark and less toxic in normal MCF-10A cells.

Enhanced sensitivity in detection of Kerr rotation by double modulation and time averaging based on Allan variance

Experiments in spintronics necessarily involve the detection of spin polarization. The sensitivity of this detection becomes an important factor to consider when extending the low temperature studies on semiconductor spintronic devices to room temperature, where the spin signal is weaker. In pump-probe experiments, which optically inject and detect spins, the sensitivity is often improved by using a photoelastic modulator (PEM) for lock-in detection. However, spurious signals can arise if diode lasers are used as optical sources in such experiments, along with a PEM. In this work, we eliminated the spurious electromagnetic coupling of the PEM onto the probe diode laser, by the double modulation technique. We also developed a test for spurious modulated interference in the pump-probe signal, due to the PEM. Besides, an order of magnitude enhancement in the sensitivity of detection of spin polarization by Kerr rotation, to 3x10(-8) rad was obtained by using the concept of Allan variance to optimally average the time series data over a period of 416 s. With these improvements, we are able to experimentally demonstrate at room temperature, photoinduced steady-state spin polarization in bulk GaAs. Thus, the advances reported here facilitate the use of diode lasers with a PEM for sensitive pump-probe experiments. They also constitute a step toward detection of spin-injection in Si at room temperature.

Synthesis, crystal structures, DNA binding and cleavage activity of L-glutamine copper(II) complexes of heterocyclic bases

Ternary L-glutamine (L-gln) copper(II) complexes [Cu(L-gln)(B)(H2O)](X) (B = 2,2'-bipyridine (bpy), X = 0.5SO(4)(2-), 1; B = 1,10-phenanthroline (phen), X = ClO4-, 2) and [Cu(L-gln)(dpq)(ClO4)] (3) (dpq, dipyridoquinoxaline) are prepared and characterized by physicochemical methods. The DNA binding and cleavage activity of the complexes have been studied. Complexes 1-3 are structurally characterized by X-ray crystallography. The complexes show distorted square pyramidal (4+1) CuN3O2 coordination geometry in which the N,O-donor amino acid and the N, N-donor heterocyclic base bind at the basal plane with a H2O or perchlorate as the axial ligand. The crystal structures of the complexes exhibit chemically significant hydrogen bonding interactions besides showing coordination polymer formation. The complexes display a d-d electronic band in the range of 610-630 nm in aqueous-dimethylformamide (DMF) solution (9:1 v/v). The quasireversible cyclic voltammetric response observed near -0.1 V versus SCE in DMF-TBAP is assignable to the Cu(II)/Cu(I) couple. The binding affinity of the complexes to calf thymus (CT) DNA follows the order: 3 (dpq) > 2 (phen) >> 1 (bpy). Complexes 2 and 3 show DNA cleavage activity in dark in the presence of 3-mercaptopropionic acid (MPA) as a reducing agent via a mechanistic pathway forming hydroxyl radical as the reactive species. The dpq complex 3 shows efficient photoinduced DNA cleavage activity on irradiation with a monochromatic UV light of 365 nm in absence of any external reagent. The cleavage efficiency of the DNA minor groove binding complexes follows the order:3 > 2 >> 1. The dpq complex exhibits photocleavage of DNA on irradiation with visible light of 647.1 nm. Mechanistic data on the photo-induced DNA cleavage reactions reveal the involvement of singlet oxygen (O-1(2)) as the reactive species in a type-II pathway. (C) 2008 Elsevier B.V. All rights reserved.

UVB irradiation alters the activities and kinetic properties of the enzymes of energy metabolism in rat lens during aging

Ultraviolet (UV) radiation is one of the major risk factors of cataract (loss of eye-lens transparency). The influence of UVB radiation (300 nm, 100 mu W cm(-2)) on the activity and apparent kinetic constants (K-m and V-max) of rat lens hexokinase (HK;EC2.7.1.1), phosphofructokinase (PFK;EC2.7.1.11), isocitrate dehydrogenase (ICDH;EC1.1.1.41) and malate dehydrogenase (MDH;EC1.1.1.37) of energy metabolism has been investigated by irradiating the lens homogenate of three-and 12-month-old rats. In the three-month-old group specific activities of HK and PFK are reduced by 56 and 43 %, respectively, and there is no change in ICDH and MDH activities after a 24 h exposure. On the other hand, in the 12-month-old group the decreases are 72, 71, 24 and 16 % for HK, PFK. ICDH and MDH, respectively. UVB irradiation increases the apparent K-m of HK and PFK (in both age groups), whereas the K-m of ICDH and MDH is not altered. While the decrease in V-max of these enzymes due to UVB exposure is only marginal in three-month-old rats, it is more pronounced (significant) in 12-month-old rats. A similar decrease in enzyme activities of HK and PFK is also observe upon UVB exposure of the intact rat lens. The photoinduced changes in energy metabolism may in turn have a bearing on lens transparency, particularly at an older age.

Copper(II) Complexes of l-Arginine as Netropsin Mimics Showing DNA Cleavage Activity in Red Light

Copper(II) complexes [Cu(L-arg)(2)](NO3)(2) (1) and [Cu(L-arg)(B)Cl]Cl (2-5), where B is a heterocyclic base, namely, 2,2'-bipyridine (bpy, 2), 1,10-phenanthroline (phen, 3), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 4), and dipyrido[3,2-a:2',3'-c)phenazine (dppz, 5), are prepared and their DNA binding and photoinduced DNA cleavage activity studied. Ternary complex 3, structurally characterized using X-ray crystallography, shows a square-pyramidal (4 + 1) coordination geometry in which the N,O-donor L-arginine and N,N-donor 1,10-phenanthroline form the basal plane with one chloride at the elongated axial site. The complex has a pendant cationic guanidinium moiety. The one-electron paramagnetic complexes display a metal-centered d-d band in the range of 590-690 nm in aqueous DMF They show quasireversible cyclic voltammetric response due to the Cu(II)/Cu(I) couple in the range of -0.1 to -0.3 V versus a saturated calomel electrode in a DMF-Tris HCl buffer (pH 7.2). The DNA binding propensity of the complexes is studied using various techniques. Copper(II) bis-arginate 1 mimics the minor groove binder netropsin by showing preferential binding to the AT-rich sequence of double-strand (ds) DNA. DNA binding study using calf thymus DNA gives an order: 5 (L-arg-dppz) >= 1 (biS-L-arg) > 4 (L-arg-dpq) > 3 (L-arg-phen) >> 2 (L-arg-bpy). Molecular docking calculations reveal that the complexes bind through extensive hydrogen bonding and electrostatic interactions with ds-DNA. The complexes cleave supercoiled pUC19 DNA in the presence of 3-mercaptopropionic acid as a reducing agent forming hydroxyl ((OH)-O-center dot) radicals. The complexes show oxidative photoinduced DNA cleavage activity in UV-A light of 365 nm and red light of 647.1 nm (Ar-Kr mixed-gas-ion laser) in a metal-assisted photoexcitation process forming singlet oxygen (O-1(2)) species in a type-II pathway. All of the complexes, barring complex 2, show efficient DNA photocleavage activity. Complexes 4 and 5 exhibit significant double-strand breaks of DNA in red light of 647.1 nm due to the presence of two photosensitizers, namely, L-arginine and dpq or dppz in the molecules.

Bile Acid Derived PET-Based Cation Sensors: Molecular Structure Dependence of their Sensitivity

A number of bile acid derived photoinduced electron transfer (PET) based sensors for metal ions are prepared. A general strategy for designing the sensor with a modular nature allows for making different molecules capable of sensing different metal ions by a change in the fluorophore and receptor unit. Keeping the basic molecular structure the same, different bile acid base fluoroionophores were prepared inorder to achieve the highest sensitivity toward the metal ions. Thesensors showed similar binding constants for the same metal ion, but the degree Of fluorescence enhancement upon addition of the metal salts were different. The sensitivities of the sensors towards a certain metal were determined from the observed fluorescence enhancement upon addition of the metal salt.

Double walled carbon nanotubes as ultrafast optical switches

Pristine and molybdenum filled double walled carbon nanotubes (DWNTs) suspended in D2O show excellent ultrafast optical switching properties investigated through femtosecond Z-scan and degenerate pump-probe method using 50 fs pulses with central photon energy of 1.57 eV. For pristine-DWNT, the two photon absorption coefficient, beta and nonlinear refraction coefficient, n2 are 4.9×10−8 cm/W, and 9.5×10−11 cm2/W, respectively, which yield one photon figure of merit, W=133 and two photon figure of merit, T=0.4. The degenerate pump-probe measurements show strong photoinduced bleaching with biexponential decay with time constants ~150 and 600 fs. ©2009 American Institute of Physics