Dinuclear Azide-Bridged Copper(II) Complex as Building Block for the Assembly of a 2D-Supramolecular Array

A novel Schiff base-copper(II) complex [Cu(2)L(2)(N(3))(2)](ClO(4))(2) 1, where L = (4-imidazolyl)ethylene-2-amino-1-ethylpyridine (apyhist), containing azide-bridges between adjacent copper ions in a dinuclear arrangement was isolated and characterized both in the solid state and in solution by X-ray crystallography and different spectroscopic techniques. Azide binding constants were estimated from titrations of the precursor [CuL(H(2)O)(2)](2+) solutions with sodium azide, giving rise to the azido-bridged species, [Cu(2)L(2)(N(3))(2)](2+). Raman spectra showed asymmetric stretching band at 2060 cm(-1), indicating the presence of azido ligands with a symmetric mu(1,) (1) binding geometry. EPA spectra, in frozen methanol/water solutions at 77 K, exhibited characteristic features of copper centers in tetragonal pyramidal coordination geometry, exhibiting magnetic interactions between them. Further, in solid state, two different values for magnetic coupling in this species were obtained, J/k = -(5.14 +/- 0.02) cm(-1) attributed to the mu(1, 1) azide-bridge mode, and J`z`/k = -(2.94 +/- 0.11) cm(-1) for the interaction between dinuclear moieties via water/perchorate bridges. Finally, an attempt was made to correlate structure and magnetic data for this dinuclear asymmetric end-on azido bridged-copper(II) 1 complex with those of another correlated dinuclear system, complex [Cu(2)L(2)Cl(2)](ClO(4))(2) 2, containing the same tridentate diimine ligand, but with chloro-bridged groups between the copper centres.

The isatin-Schiff base copper(II) complex Cu(isaepy)(2) acts as delocalized lipophilic cation, yields widespread mitochondrial oxidative damage and induces AMP-activated protein kinase-dependent apoptosis

We previously demonstrated that Bis[(2-oxindol-3-ylimino)-2-(2-aminoethyl) pyridine-N, N`] copper(II) [Cu(isaepy)(2)] was an efficient inducer of the apoptotic mitochondrial pathway. Here, we deeply dissect the mechanisms underlying the ability of Cu(isaepy)(2) to cause mitochondriotoxicity. In particular, we demonstrate that Cu(isaepy)(2) increases NADH-dependent oxygen consumption of isolated mitochondria and that this phenomenon is associated with oxy-radical production and insensitive to adenosine diphosphate. These data indicate that Cu(isaepy)(2) behaves as an uncoupler and this property is also confirmed in cell systems. Particularly, SH-SY5Y cells show: (i) an early loss of mitochondrial transmembrane potential; (ii) a decrease in the expression levels of respiratory complex components and (iii) a significant adenosine triphosphate (ATP) decrement. The causative energetic impairment mediated by Cu(isaepy)(2) in apoptosis is confirmed by experiments carried out with rho(0) cells, or by glucose supplementation, where cell death is significantly inhibited. Moreover, gastric and cervix carcinoma AGS and HeLa cells, which rely most of their ATP production on oxidative phosphorylation, show a marked sensitivity toward Cu(isaepy)(2). Adenosine monophosphate-activated protein kinase (AMPK), which is activated by events increasing the adenosine monophosphate: ATP ratio, is deeply involved in the apoptotic process because the overexpression of its dominant/negative form completely abolishes cell death. Upon glucose supplementation, AMPK is not activated, confirming its role as fuel-sensing enzyme that positively responds to Cu(isaepy)(2)-mediated energetic impairment by committing cells to apoptosis. Overall, data obtained indicate that Cu(isaepy)(2) behaves as delocalized lipophilic cation and induces mitochondrial-sited reactive oxygen species production. This event results in mitochondrial dysfunction and ATP decrease, which in turn triggers AMPK-dependent apoptosis.

FT-Raman, FTIR and density functional theory studies of a hydrogen-bonded formamide: pyridine complex

Raman and IR experiments have been carried out on formamide (FA) and pyridine (Py) mixtures at different compositions. The appearance of a new Raman band at 996 cm(-1) (nu(1) region of Py), whose intensity depends on the FA concentration, is assigned to an FA: Py adduct and this result is in excellent agreement with those of other authors who employed noisy light-based coherent Raman scattering spectroscopy (I((2)) CARS). Another band at 1587 cm(-1) (nu(8) region of Py) has been observed for the first time by using Raman and IR spectroscopies. Its intensity shows the same dependence on the FA concentration and this fact allows us to also attribute it to an FA: Py adduct. The good relationship between the Raman and IR data demonstrates the potential of the vibrational spectroscopy for this kind of study. Owing to higher absolute Raman scattering cross section, the nu(1) region of Py has been chosen for the quantitative analysis and a stoichiometry of 1 : 1 FA: Py is reported. The experimental data are very well supported by the density functional theory (OFT) calculation, which was employed for the first time to the present system. Furthermore, the actual investigation shows an excellent agreement with those reported from computational calculations for similar systems. A comparison with our previous studies confirms that: the solvent dielectric constant determines the stoichiometry of a given Lewis acid-base adduct in the infinite dilution limit. Copyright (C) 2009 John Wiley & Sons, Ltd.

Synthesis, characterization and biological analysis of the complex [VO(Hdhp)(2)] (H(2)dhp=2,3-dihydroxypyridine)

A new vanadium (IV) complex with the monoanion of 2,3-dihydroxypyridine (H(2)dhp), or 3-hydroxy-2(1H)-pyridone, was synthesized, characterized by physicochemical techniques and tested biologically. The EPR data for the [VO(Hdhp)(2)] complex in DMF are: g(x) = 1.9768, g(y) = 1.9768 and g(z) = 1.9390; A values (10(-4) cm(-1)): A(x), 59.4; A(y//), 59.4; A(z), 171.0. The vV=O band in the IR spectrum of the complex is at 986 cm(-1). The complex is paramagnetic, with mu(eff) = 1.65 BM (d(1), spin-only) at 25 degrees C. The irreversible oxidation process [V(V)/V(IV)] of the [VO(Hdhp)(2)] complex, as revealed in a cyclic voltammogram, occurs at 876 mV. The calculated molecular structure of [VO(Hdhp)(2)] shows the vanadium(IV) center in a distorted square pyramidal environment, with the oxo ligand in the apical position and the oxygen donor atoms of the Hdhp ligands in the basal positions. The ability of [VO(Hdhp)(2)] to mimic insulin, and its toxicity to hepato-biliary functions, were investigated in streptozotocin-induced diabetic rats and it was concluded that the length of treatment and the amount of [VO(Hdhp)(2)] administered were effective in reducing experimental diabetes.

How does data quality in a network affect heuristic solutions?

To have good data quality with high complexity is often seen to be important. Intuition says that the higher accuracy and complexity the data have the better the analytic solutions becomes if it is possible to handle the increasing computing time. However, for most of the practical computational problems, high complexity data means that computational times become too long or that heuristics used to solve the problem have difficulties to reach good solutions. This is even further stressed when the size of the combinatorial problem increases. Consequently, we often need a simplified data to deal with complex combinatorial problems. In this study we stress the question of how the complexity and accuracy in a network affect the quality of the heuristic solutions for different sizes of the combinatorial problem. We evaluate this question by applying the commonly used p-median model, which is used to find optimal locations in a network of p supply points that serve n demand points. To evaluate this, we vary both the accuracy (the number of nodes) of the network and the size of the combinatorial problem (p). The investigation is conducted by the means of a case study in a region in Sweden with an asymmetrically distributed population (15,000 weighted demand points), Dalecarlia. To locate 5 to 50 supply points we use the national transport administrations official road network (NVDB). The road network consists of 1.5 million nodes. To find the optimal location we start with 500 candidate nodes in the network and increase the number of candidate nodes in steps up to 67,000 (which is aggregated from the 1.5 million nodes). To find the optimal solution we use a simulated annealing algorithm with adaptive tuning of the temperature. The results show that there is a limited improvement in the optimal solutions when the accuracy in the road network increase and the combinatorial problem (low p) is simple. When the combinatorial problem is complex (large p) the improvements of increasing the accuracy in the road network are much larger. The results also show that choice of the best accuracy of the network depends on the complexity of the combinatorial (varying p) problem.

Agent-Oriented Data Curation in Bioinformatics

The practitioners of bioinformatics require increasing sophistication from their software tools to take into account the particular characteristics that make their domain complex. For example, there is a great variation of experience of researchers, from novices who would like guidance from experts in the best resources to use to experts that wish to take greater management control of the tools used in their experiments. Also, the range of available, and conflicting, data formats is growing and there is a desire to automate the many trivial manual stages of in-silico experiments. Agent-oriented software development is one approach to tackling the design of complex applications. In this paper, we argue that, in fact, agent-oriented development is a particularly well-suited approach to developing bioinformatics tools that take into account the wider domain characteristics. To illustrate this, we design a data curation tool, which manages the format of experimental data, extend it to better account for the extra requirements placed by the domain characteristics, and show how the characteristics lead to a system well suited to an agent-oriented view.

Agent-Oriented Data Curation in Bioinformatics

The practitioners of bioinformatics require increasing sophistication from their software tools to take into account the particular characteristics that make their domain complex. For example, there is a great variation of experience of researchers, from novices who would like guidance from experts in the best resources to use to experts that wish to take greater management control of the tools used in their experiments. Also, the range of available, and conflicting, data formats is growing and there is a desire to automate the many trivial manual stages of in-silico experiments. Agent-oriented software development is one approach to tackling the design of complex applications. In this paper, we argue that, in fact, agent-oriented development is a particularly well-suited approach to developing bioinformatics tools that take into account the wider domain characteristics. To illustrate this, we design a data curation tool, which manages the format of experimental data, extend it to better account for the extra requirements placed by the domain characteristics, and show how the characteristics lead to a system well suited to an agent-oriented view.

Parameterization Of Turbulence Models Using 3DVAR Data Assimilation

In this research the 3DVAR data assimilation scheme is implemented in the numerical model DIVAST in order to optimize the performance of the numerical model by selecting an appropriate turbulence scheme and tuning its parameters. Two turbulence closure schemes: the Prandtl mixing length model and the two-equation k-ε model were incorporated into DIVAST and examined with respect to their universality of application, complexity of solutions, computational efficiency and numerical stability. A square harbour with one symmetrical entrance subject to tide-induced flows was selected to investigate the structure of turbulent flows. The experimental part of the research was conducted in a tidal basin. A significant advantage of such laboratory experiment is a fully controlled environment where domain setup and forcing are user-defined. The research shows that the Prandtl mixing length model and the two-equation k-ε model, with default parameterization predefined according to literature recommendations, overestimate eddy viscosity which in turn results in a significant underestimation of velocity magnitudes in the harbour. The data assimilation of the model-predicted velocity and laboratory observations significantly improves model predictions for both turbulence models by adjusting modelled flows in the harbour to match de-errored observations. 3DVAR allows also to identify and quantify shortcomings of the numerical model. Such comprehensive analysis gives an optimal solution based on which numerical model parameters can be estimated. The process of turbulence model optimization by reparameterization and tuning towards optimal state led to new constants that may be potentially applied to complex turbulent flows, such as rapidly developing flows or recirculating flows.

Development and pharmacological evaluation of ropivacaine-2-hydroxypropyl-beta-cyclodextrin inclusion complex

Ropivacaine (RVC) is an enantiomerically pure local anesthetic (LA) largely used in surgical procedures, which presents physico-chemical and therapeutic properties similar to those of bupivacaine (BPV), but associated to less systemic toxicity This study focuses on the development and pharmacological evaluation of a RVC in 2-hydroxypropyl-beta-cyclodextrin (HP-P-CD) inclusion complex. Phase-solubility diagrams allowed the determination of the association constant between RVC and HP-beta-CD (9.46 M-1) and showed an increase on RVC solubility upon complexation. Release kinetics revealed a decrease on RVC release rate and reduced hemolytic effects after complexation. (onset at 3.7 mM and 11.2 mM for RVC and RVCHP-beta-CD, respectively) were observed. Differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and X-ray analysis (X-ray) showed the formation and the morphology of the complex. Nuclear magnetic resonance (NMR) and job-plot experiments afforded data regarding inclusion complex stoichiometry (1:1) and topology. Sciatic nerve blockade studies showed that RVCHP-beta-CD was able to reduce the latency without increasing the duration of motor blockade, but prolonging the duration and intensity of the sensory blockade (p < 0.001) induced by the LA in mice. These results identify the RVCHP-beta-CD complex as an effective novel approach to enhance the pharmacological effects of RVC, presenting it as a promising new anesthetic formulation. (c) 2007 Elsevier B.V All rights reserved.

Elucidating the Evolution of the Red Brocket Deer Mazama americana Complex (Artiodactyla; Cervidae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Langmuir and Langmuir-Blodgett films containing a porphyrin-ruthenium complex

The fabrication of supramolecular structures from the tetraruthenated porphyrin-containing phosphines, {TPyP[RuCl3(dppb)](4)}, RuTPyP, is demonstrated with Langmuir and Langmuir-Blodgett films. The surface pressure-molecular area isotherms (pi-A) point to an edge-on arrangement for the RuTPyP molecules in the condensed state. Weak aggregation in the Langmuir films was indicated by non-zero surface potentials at large areas per molecule and a slight red shift in the ultraviolet-visible absorption spectrum in comparison to the spectrum in solution. Further aggregation occurs in the Z-type Lang muir-Blodgett films, which was confirmed with ultraviolet-visible spectroscopy of the deposited films. Fourier transform infrared and Raman spectroscopic data for powder and Langmuir-Blodgett films indicate that the RuTPyP molecules are chemically stable in Langmuir-Blodgett films regardless of the contact with water during film fabrication. The nanostructured nature of the Langmuir-Blodgett films was manifested in cyclic voltammetry due to the high sensitivity of the metallic centers in RuTPyR Electrodes modified with Langmuir-Blodgett films exhibit an anodic peak at 100 mV and a cathodic peak at 7 mV, which is assigned to RuIII/RuII redox processes. Furthermore, Langmuir-Blodgett films from RuTPyP showed electrocatalytic activity for oxidation of benzyl alcohol, illustrated by a large shift of 100 mV in the anodic peak at 400 mV, while electropolymerized and cast films of the same compound displayed smaller and no activities, respectively.

Analysis of the Al-PANI interfaces by complex impedance spectroscopy

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Synthesis, characterization and biological analysis of the complex [VO(Hdhp)(2)] (H(2)dhp=2,3-dihydroxypyridine)

A new vanadium (IV) complex with the monoanion of 2,3-dihydroxypyridine (H(2)dhp), or 3-hydroxy-2(1H)-pyridone, was synthesized, characterized by physicochemical techniques and tested biologically. The EPR data for the [VO(Hdhp)(2)] complex in DMF are: g(x) = 1.9768, g(y) = 1.9768 and g(z) = 1.9390; A values (10(-4) cm(-1)): A(x), 59.4; A(y//), 59.4; A(z), 171.0. The vV=O band in the IR spectrum of the complex is at 986 cm(-1). The complex is paramagnetic, with mu(eff) = 1.65 BM (d(1), spin-only) at 25 degrees C. The irreversible oxidation process [V(V)/V(IV)] of the [VO(Hdhp)(2)] complex, as revealed in a cyclic voltammogram, occurs at 876 mV. The calculated molecular structure of [VO(Hdhp)(2)] shows the vanadium(IV) center in a distorted square pyramidal environment, with the oxo ligand in the apical position and the oxygen donor atoms of the Hdhp ligands in the basal positions. The ability of [VO(Hdhp)(2)] to mimic insulin, and its toxicity to hepato-biliary functions, were investigated in streptozotocin-induced diabetic rats and it was concluded that the length of treatment and the amount of [VO(Hdhp)(2)] administered were effective in reducing experimental diabetes.

Prevalence and antifungal susceptibility of Candida parapsilosis complex isolates collected from oral cavities of HIV-infected individuals

At present, few data are available on the prevalence and antifungal susceptibility of Candida parapsilosis complex isolates from HIV-infected individuals. The C. parapsilosis complex comprises three species, C. parapsilosis sensu stricto, C. metapsilosis and C. orthopsilosis. Fifteen of 318 Candida isolates were identified as members of the C. parapsilosis complex by PCR and restriction fragment length polymorphism (RFLP). The prevalence of C. parapsilosis complex isolates was 4.7 %, 2.2 % being identified as C. parapsilosis sensu stricto and 2.5% as C. metapsilosis, while no C. orthopsilosis was isolated. This is believed to be the first study that has identified isolates of C. metapsilosis obtained from the oral cavity of HIV-infected individuals. Antifungal susceptibility tests indicated that all the isolates were susceptible to amphotericin B (AMB), fluconazole (FLC), ketoconazole (KTC), itraconazole (ITC), voriconazole (VRC) and caspofungin (CASPO). Although isolates of C. parapsilosis sensu stricto and C. metapsilosis were susceptible to FLC, isolates of C. metapsilosis showed a tendency for higher MICs (>= 1.0 mu g ml(-1)). Based upon the frequency of candidiasis and the fact that certain isolates of the C. parapsilosis complex respond differently to FLC therapy, our data may be of therapeutic relevance with respect to susceptibility and potential resistance to specific antifungal agents. Our data suggest that C. metapsilosis can be a human commensal; its importance as a pathogen has yet to be confirmed.

Complex meiotic configuration of the holocentric chromosomes: the intriguing case of the scorpion Tityus bahiensis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)