Significant photocytotoxic effect of an iron(III) complex of a Schiff base ligand derived from vitamin B-6 and thiosemicarbazide in visible light

Iron(III)-Schiff base complexes, namely, Fe(tsc-py)(2)](NO3) (1), Fe(tsc-acpy)(2)](NO3) (2) and Fe(tsc-VB6)(2)](NO3) (3), where tsc-py, tsc-acpy and tsc-VB6 are the respective Schiff bases derived from thiosemicarbazide (tsc) and pyridine-2-aldehyde (tsc-py), 2-acetyl pyridine (tsc-acpy) and vitamin B-6 (pyridoxal, tsc-VB6), have been prepared, structurally characterized and their photocytotoxicity studied in cancer HeLa cells. The single crystal X-ray structures of the complexes 1 and 2 show a distorted octahedral geometry formed by the FeN4S2 core. The low-spin and 1 : 1 electrolytic complexes display a broad absorption band in the visible region. Complexes 1 and 2, without any VB6 moiety are not cytotoxic under light or dark conditions. Complex 3 is significantly photocytotoxic under visible light of 400-700 nm giving an IC50 value of 22.5 mu M in HeLa cells with no dark toxicity (IC50 > 100 mu M). The photo-induced cell death is attributable to apoptotic pathways involving photo-assisted generation of intracellular ROS. The observed photocytotoxicity of complex 3 could be the result of its better photosensitizing property combined with its enhanced uptake into cancer cells via a VB6 transporting membrane carrier (VTC) mediated diffusion pathway due to the presence of the VB6 moiety compared to the two non-vitamin B-6 analogues, complexes 1 and 2.

Implication of a sigma-Methane Complex en Route to Elimination of Methane from a Ruthenium Complex: An Experimental and Theoretical Investigation

The five-coordinated 16-electron complex Ru(Me)(dppe)(2)]OTf] (3) undergoes methane elimination at room temperature to afford the ortho-metalated species (dppe){(C6H5)(C6H4)PCH2CH2P(C6H5)(2)}Ru]OTf] (7). Methane elimination, monitored using NMR spectroscopy, revealed no intermediate throughout the reaction. The NOE between Ru-Me protons and ortho phenyl protons and an agostic interaction trans to the methyl group were found in complex 3 by NMR spectroscopy, which form the basis for three plausible pathways for methane elimination and ortho metalation: pathway I (through spatial interaction), pathway II (through oxidative addition and reductive elimination), and pathway III (through agostic interaction). Methane elimination from complex 3 via pathway I was discounted, since it involves interactions through space and not through bonds. Moreover, the calculated energy barrier for the pathway I transition state was quite high (71.3 kcal/mol), which also indicates that this pathway is very unlikely. Furthermore, no spectroscopic evidence for oxidatively added seven-coordinated Ru(IV) species was found and the computed energy barrier of the transition state for pathway II was moderately high (41.1 kcal/mol), which suggests that this cannot be the right pathway for methane elimination and ortho-metalation of complex 3. On the other hand, indirect evidence in the form of chemical reactions point to the most plausible pathway for methane elimination, pathway III, via the intermediacy of a sigma-CH4 complex that could not be found spectroscopically. DFT calculations at several levels on this pathway showed an initial low-barrier rearrangement through TS1 to a square-pyramidal intermediate wherein methyl and agostic C-H are cis to each other. Migration of hydrogen from agostic C-H and elimination of methane proceed through the transition state TS2, which retains a weak metal-H bonding through most parts of the reaction coordinate. Upon comparison of all three pathways, pathway III was found to be the most likely for methane elimination and ortho-metalation of complex 3.

Impacts of climate change and management responses in tropical forests depend on complex frugivore-mediated seed dispersal

AimBiodiversity outcomes under global change will be influenced by a range of ecological processes, and these processes are increasingly being considered in models of biodiversity change. However, the level of model complexity required to adequately account for important ecological processes often remains unclear. Here we assess how considering realistically complex frugivore-mediated seed dispersal influences the projected climate change outcomes for plant diversity in the Australian Wet Tropics (all 4313 species). LocationThe Australian Wet Tropics, Queensland, Australia. MethodsWe applied a metacommunity model (M-SET) to project biodiversity outcomes using seed dispersal models that varied in complexity, combined with alternative climate change scenarios and habitat restoration scenarios. ResultsWe found that the complexity of the dispersal model had a larger effect on projected biodiversity outcomes than did dramatically different climate change scenarios. Applying a simple dispersal model that ignored spatial, temporal and taxonomic variation due to frugivore-mediated seed dispersal underestimated the reduction in the area of occurrence of plant species under climate change and overestimated the loss of diversity in fragmented tropical forest remnants. The complexity of the dispersal model also changed the habitat restoration approach identified as the best for promoting persistence of biodiversity under climate change. Main conclusionsThe consideration of complex processes such as frugivore-mediated seed dispersal can make an important difference in how we understand and respond to the influence of climate change on biodiversity.

Visible light-induced cytotoxicity of a dinuclear iron(III) complex of curcumin with low-micromolar IC50 value in cancer cells

Photoactive metal complexes have emerged as potential candidates in the photodynamic therapy (PDT) of cancer. We present here the synthesis, characterization and visible light-triggered anticancer activity of two novel mixed-ligand oxo-bridged iron(III) complexes, viz., {Fe(L)(acac)}(2)(mu-O)](ClO4)(2) (1) and {Fe (L)(cur)}(2)(mu-O)](ClO4)(2) (2) where L is bis-(2-pyridylmethyl)-benzylamine, acac is acetylacetonate and cur is the monoanion of curcumin (bis(4-hydroxy-3-methoxyphenyl)-1,6-diene-3,5-dione). The crystal structure of complex 1 (as PF6 salt, 1a) shows distorted octahedral geometry of each iron(III) centre formed by the FeN3O3 core. The 1: 2 electrolytic complexes are stable in solution and retain their oxo-bridged identity in aqueous medium. Complex 2 has a strong absorption band in the visible region and shows promising photocytotoxicity in HeLa and MCF-7 cancer cells in visible light giving respective IC50 values of 3.1 +/- 0.4 lM and 4.9 +/- 0.5 lM while remains non-toxic in the dark (IC50 > 50 lM). The control complex 1 is inactive both in the light and dark. Complex 2 accumulates in cytoplasm of HeLa and MCF-7 cells as evidenced from fluorescence microscopy and triggers apoptotic cell death via light-assisted generation of reactive oxygen species (ROS). Taken together, complex 2 with its promising photocytotoxicity but negligible dark toxicity in cancer cells has significant photochemotherapeutic potential for applications in PDT. (C) 2015 Elsevier B.V. All rights reserved.

Mitochondrial selectivity and remarkable photocytotoxicity of a ferrocenyl neodymium(III) complex of terpyridine and curcumin in cancer cells

A series of four novel neodymium(III) complexes of the formulation Nd(R-tpy)(O-O)(NO3)(2)] (1-4), where R-tpy is 4'-phenyl-2,2': 6', 2''-terpyridine (Ph-tpy; 1, 2) and 4'-ferrocenyl-2,2': 6', 2''-terpyridine (Fc-tpy; 3, 4); O-O is the conjugate base of acetylacetone (Hacac; 1, 3) or curcumin (Hcurc; 2, 4), are synthesized and characterized. The single crystal structure of 1 shows that the complex is a discrete mononuclear species with the Nd(III) centre in a nine coordinate environment provided by a set of O6N3 donor atoms. Complexes 1 and 3 having the simple acac ligand are prepared as control compounds. Complex 4, possessing an appended ferrocenyl (Fc) and the curcumin moiety, is remarkably photocytotoxic to HeLa and MCF-7 cancer cells in visible light giving respective IC50 values of 0.7 mu M and 2.1 mu M while being significantly less toxic to MCF-10A normal cells (IC50 = 34 mu M) and in the dark (IC50 > 50 mu M). The phenyl appended complex 2, lacking a ferrocenyl moiety, is significantly less toxic to both the cell lines when compared with 4. Complexes 1 and 3, lacking the photoactive curcumin moiety, do not show any apparent toxicity both in light and in the dark. The cell death is apoptotic in nature and is mediated by the light-induced formation of reactive oxygen species (ROS). Fluorescence imaging experiment with HeLa cells reveals mitochondrial accumulation of complex 4 within 4 h of incubation. The complexes bind to calf thymus (ct) DNA with moderate affinity giving K-b values in the range of 10(4)-10(5) M-1. The curcumin complexes 2 and 4 cleave plasmid supercoiled DNA to its nicked circular form in visible light via O-1(2) and (OH)-O-center dot pathways. The presence of the ferrocenyl moiety is likely to be responsible for the enhanced cellular uptake and photocytotoxicity of complex 4. Thus, the mitochondria targeting complex 4, being remarkably cytotoxic in light but non-toxic in the dark and to normal cells, is a potential candidate for photochemotherapeutic applications.

Synthetic scope and DFT analysis of the chiral binap-gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

he 1,3-dipolar cycloaddition between glycine-derived azlactones with maleimides is efficiently catalyzed by the dimeric chiral complex [(S-a)-Binap.AuTFA](2). The alanine-derived oxazolone only reacts with tert-butyl acrylate giving anomalous regiochemistry, which is explained and supported by Natural Resonance Theory and Nucleus Independent Chemical Shifts calculations. The origin of the high enantiodiscrimination observed with maleimides and tert-butyl acrylate is analyzed using DFT computed at M06/Lanl2dz//ONIOM(b3lyp/Lanl2dz:UFF) level. Several applications of these cycloadducts in the synthesis of new proline derivatives with a 2,5-trans-arrangement and in the preparation of complex fused polycyclic molecules are described.

Analysis of Spanish text-thesaurus as a complex network

[EN]Based on the theoretical tools of Complex Networks, this work provides a basic descriptive study of a synonyms dictionary, the Spanish Open Thesaurus represented as a graph. We study the main structural measures of the network compared with those of a random graph. Numerical results show that Open-Thesaurus is a graph whose topological properties approximate a scale-free network, but seems not to present the small-world property because of its sparse structure. We also found that the words of highest betweenness centrality are terms that suggest the vocabulary of psychoanalysis: placer (pleasure), ayudante (in the sense of assistant or worker), and regular (to regulate).

A complex systems modelling approach for decentralized simulation of electrical microgrids

ICECCS 2010

Terahertz time domain spectroscopy of amino acids and sugars

A time-domain spectrometer for use in the terahertz (THz) spectral range was designed and constructed. Due to there being few existing methods of generating and detecting THz radiation, the spectrometer is expected to have vast applications to solid, liquid, and gas phase samples. In particular, knowledge of complex organic chemistry and chemical abundances in the interstellar medium (ISM) can be obtained when compared to astronomical data. The THz spectral region is of particular interest due to reduced line density when compared to the millimeter wave spectrum, the existence of high resolution observatories, and potentially strong transitions resulting from the lowest-lying vibrational modes of large molecules.

The heart of the THz time-domain spectrometer (THz-TDS) is the ultrafast laser. Due to the femtosecond duration of ultrafast laser pulses and an energy-time uncertainty relationship, the pulses typically have a several-THz bandwidth. By various means of optical rectification, the optical pulse carrier envelope shape, i.e. intensity-time profile, can be transferred to the phase of the resulting THz pulse. As a consequence, optical pump-THz probe spectroscopy is readily achieved, as was demonstrated in studies of dye-sensitized TiO₂, as discussed in chapter 4. Detection of the terahertz radiation is commonly based on electro-optic sampling and provides full phase information. This allows for accurate determination of both the real and imaginary index of refraction, the so-called optical constants, without additional analysis. A suite of amino acids and sugars, all of which have been found in meteorites, were studied in crystalline form embedded in a polyethylene matrix. As the temperature was varied between 10 and 310 K, various strong vibrational modes were found to shift in spectral intensity and frequency. Such modes can be attributed to intramolecular, intermolecular, or phonon modes, or to some combination of the three.

The use of role-play games in teaching: The International Climate Negotiation Game

This paper presents a role-play game designed by the authors, which focuses on international climate negotiations. The game has been used at a university with students all drawn from the same course and at summer schools with students from different levels (undergraduate, master’s and doctoral students and post-doctoral researchers) and different knowledge areas (economics, law, engineering, architecture, biology and others). We discuss how the game fits into the process of competence-based learning, and what benefits games, and role-play games in particular, have for teaching. In the game, students take on the role of representatives of national institutions and experience at first hand a detailed process of international negotiation concerned with climate change.

A theory of slow feature analysis for transformation-based input signals with an application to complex cells

We develop a group-theoretical analysis of slow feature analysis for the case where the input data are generated by applying a set of continuous transformations to static templates. As an application of the theory, we analytically derive nonlinear visual receptive fields and show that their optimal stimuli, as well as the orientation and frequency tuning, are in good agreement with previous simulations of complex cells in primary visual cortex (Berkes and Wiskott, 2005). The theory suggests that side and end stopping can be interpreted as a weak breaking of translation invariance. Direction selectivity is also discussed. © 2011 Massachusetts Institute of Technology.

Guidance of collective cell migration by substrate geometry.

Collective behavior refers to the emergence of complex migration patterns over scales larger than those of the individual elements constituting a system. It plays a pivotal role in biological systems in regulating various processes such as gastrulation, morphogenesis and tissue organization. Here, by combining experimental approaches and numerical modeling, we explore the role of cell density ('crowding'), strength of intercellular adhesion ('cohesion') and boundary conditions imposed by extracellular matrix (ECM) proteins ('constraints') in regulating the emergence of collective behavior within epithelial cell sheets. Our results show that the geometrical confinement of cells into well-defined circles induces a persistent, coordinated and synchronized rotation of cells that depends on cell density. The speed of such rotating large-scale movements slows down as the density increases. Furthermore, such collective rotation behavior depends on the size of the micropatterned circles: we observe a rotating motion of the overall cell population in the same direction for sizes of up to 200 μm. The rotating cells move as a solid body, with a uniform angular velocity. Interestingly, this upper limit leads to length scales that are similar to the natural correlation length observed for unconfined epithelial cell sheets. This behavior is strongly altered in cells that present a downregulation of adherens junctions and in cancerous cell types. We anticipate that our system provides a simple and easy approach to investigate collective cell behavior in a well-controlled and systematic manner.

Estimation of Transverse Thermal Conductivity of Doubly-periodic Fiber Reinforced Composites

For steady-state heat conduction a new variational functional for a unit cell of composites with periodic microstructures is constructed by considering the quasi-periodicity of the temperature field and in the periodicity of the heat flux fields. Then by combining with the eigenfunction expansion of complex potential which satisfies the fiber-matrix interface conditions, an eigenfunction expansion-variational method (EEVM) based on a unit cell is developed. The effective transverse thermal conductivities of doubly-periodic fiber reinforced composites are calculated, and the first-order approximation formula for the square and hexagonal arrays is presented,which is convenient for engineering application. The numerical results show a good convergency of the presented method, even through the fiber volume fraction is relatively high. Comparisons with the existing analytical and experimental results are made to demonstrate the accuracy and validity of the first-order approximation formula for the hexagonal array.

Calculation of the bulk modulus of simple and complex crystals with the chemical bond method

The relation between the lattice energies and the bulk moduli on binary inorganic crystals was studied, and the concept of lattice energy density is introduced. We find that the lattice energy densities are in good linear relation with the bulk moduli in the same type of crystals, the slopes of fitting lines for various types of crystals are related to the valence and coordination number of cations of crystals, and the empirical expression of calculated slope is obtained. From crystal structure, the calculated results are in very good agreement with the experimental values. At the same time, by means of the dielectric theory of the chemical bond and the calculating method of the lattice energy of complex crystals, the estimative method of the bulk modulus of complex crystals was established reasonably, and the calculated results are in very good agreement with the experimental values.

Improvement of amplified spontaneous emission performance by doping tris(8-hydroxyquinoline) aluminum (Alq3) in dye-doped polymer thin films

A well-known red fluorescent dye 4-(dicy-anomethylene)-2-t-butyl-6(1,1,7,7-tetramethyljulolidyl-9-enyl)4H-pyran (DCJTB) was codoped with an electron transport organic molecule tris(8-hydroxyquinohne) aluminum (Alq3) in a host matrix of polystyrene (PS), and the amplified spontaneous emission (ASE) was studied by optically pumping. It was found that the ASE performance was significantly improved by the introduction of Alq3. The Alq3:DCJTB:PS blending thin films showed a low threshold (2.4 mu J/pulse) and a high net gain coefficient (109.95 cm(-1)) compared with the pure DCJTB:PS system (threshold of 15.2 mu J/pulse and gain of 35.94 cm(-1)). The improvement of the ASE performance was considered to be attributable to the effective Foster energy transfer from Alq(3) to DCJTB. Our results demonstrate that the Alq(3):DCJTB could be a promising candidate as gain medium for red organic diode lasers.