Telma F. S. Silva

Cobalt complexes bearing scorpionate ligands: synthesis, characterization, cytotoxicity and DNA cleavage

A number of novel, water-stable redox-active cobalt complexes of the C-functionalized tripodal ligands tris(pyrazolyl)methane XC(pz)(3) (X = HOCH(2), CH(2)OCH(2)Py or CH(2)OSO(2)Me) are reported along with their effects on DNA. The compounds were isolated as air-stable solids and fully characterized by IR and FIR spectroscopies, ESI-MS(+/-), cyclic voltammetry, controlled potential electrolysis, elemental analysis and, in a number of cases, also by single-crystal X-ray diffraction. They showed moderate cytotoxicity in vitro towards HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma human cancer cell lines. This viability loss is correlated with an increase of tumour cell lines apoptosis. Reactivity studies with biomolecules, such as reducing agents, H(2)O(2), plasmid DNA and UV-visible titrations were also performed to provide tentative insights into the mode of action of the complexes. Incubation of Co(II) complexes with pDNA induced double strand breaks, without requiring the presence of any activator. This pDNA cleavage appears to be mediated by O-centred radical species.

Scorpionate complexes of vanadium(III or IV) as catalyst precursors for solvent-free cyclohexane oxidation with dioxygen*

The V-scorpionate vanadium complexes [VCl3{HC(pz)3}] (pz = pyrazolyl) and [VCl3{SO3C(pz)3}] catalyze cyclohexane oxidation with dioxygen, to cyclohexanol (the main product) and cyclohexanone, under solvent-free conditions. [VCl3{HC(pz)3}] provides the best activity (13 % conversion into the ketone and alcohol, with high selectivity, at the O2 pressure of 15 atm, at 140 ºC, 18 h reaction time). The reaction is further promoted (to 15 % conversion) by pyrazinecarboxylic acid (PCA). The use of C- or O-radical traps supports the involvement of a free-radical reaction mechanism. Several reaction parameters have been varied in a systematic study, directed toward optimization of the process.

Biological characterization of the antiproliferative potential of Co(II) and Sn(IV) coordination compounds in human cancer cell lines: a comparative proteomic approach.

Abstract Background: The discovery of cisplatin’s antitumor activity led to a great interest in the potential application of coordination compounds as chemotherapeutic agents. It is essential to identify new compounds that selectively inhibit tumor proliferation, evading secondary effects and resistance associated with chemotherapeutics. Methods: The in vitro antiproliferative potential of an organotin(IV) compound was evaluated using colorectal and hepatocellular carcinoma, mammary gland adenocarcinoma cell lines, and human fibroblasts. Tumor cell death was evaluated by fluorescence microscopy and flow cytometry for the Sn(IV) compound and also for a Co(II) compound bearing 1,10-phenanthroline-5,6-dione as ligand. Comparative proteomic analysis for both compounds was assessed in the colorectal cancer cell line. Results: The Sn(IV) compound presented a high cytotoxic effect in colorectal and hepatocellular carcinoma cell lines (IC50 of 0.238±0.011 μM, 0.199±0.003 μM, respectively), and a lower cytotoxicity in human fibroblasts. Both compounds induced cell apoptosis and promoted the overexpression of oxidative stress-related enzyme superoxide dismutase [Cu-Zn] (SODC). The Co(II) compound induced a decreased expression of anti-apoptotic proteins (translationally-controlled tumor protein and endoplasmin), and the Sn(IV) compound decreased expression of proteins involved in microtubule stabilization, TCTP, and cofilin-1. Conclusions: Our data reveals a high in vitro antiproliferative potential against cancer cell lines and a moderate selectivity promoted by the Sn(IV) compound. Proteomic analysis of Sn(IV) and Co(II) compounds in the colorectal cancer cell line allowed an insight to their mechanisms of action, particularly by affecting the expression of proteins typically deregulated in cancer, and also suggesting a promising therapeutic potential for both compounds.

Cobalt Complexes with Pyrazole Ligands as Catalyst Precursors for the Peroxidative Oxidation of Cyclohexane: X‐ray Absorption Spectroscopy Studies and Biological Applications

[CoCl(μ-Cl)(Hpz(Ph))3]2 (1) and [CoCl2(Hpz(Ph))4] (2) were obtained by reaction of CoCl2 with HC(pz(Ph))3 and Hpz(Ph), respectively (Hpz(Ph)=3-phenylpyrazole). The compounds were isolated as air-stable solids and fully characterized by IR and far-IR spectroscopy, MS(ESI+/-), elemental analysis, cyclic voltammetry (CV), controlled potential electrolysis, and single-crystal X-ray diffraction. Electrochemical studies showed that 1 and 2 undergo single-electron irreversible Co(II)→Co(III) oxidations and Co(II)→Co(I) reductions at potentials measured by CV, which also allowed, in the case of dinuclear complex 1, the detection of electronic communication between the Co centers through the chloride bridging ligands. The electrochemical behavior of models of 1 and 2 were also investigated by density functional theory (DFT) methods, which indicated that the vertical oxidation of 1 and 2 (that before structural relaxation) affects mostly the chloride and pyrazolyl ligands, whereas adiabatic oxidation (that after the geometry relaxation) and reduction are mostly metal centered. Compounds 1 and 2 and, for comparative purposes, other related scorpionate and pyrazole cobalt complexes, exhibit catalytic activity for the peroxidative oxidation of cyclohexane to cyclohexanol and cyclohexanone under mild conditions (room temperature, aqueous H2O2). In situ X-ray absorption spectroscopy studies indicated that the species derived from complexes 1 and 2 during the oxidation of cyclohexane (i.e., Ox-1 and Ox-2, respectively) are analogous and contain a Co(III) site. Complex 2 showed low in vitro cytotoxicity toward the HCT116 colorectal carcinoma and MCF7 breast adenocarcinoma cell lines.

Synthesis and Coordination Chemistry of a New N-4-Polydentate Class of Pyridyl-Functionalized Scorpionate Ligands: Complexes of Fe-II, Zn-II, V-IV, Pd-II and Use for Heterobimetallic Systems

The new potentially N(4)-multidentate pyridyl-functionalized scorpionates 4-((tris-2,2,2-(pyrazol-1-yl)ethoxy)methyl)pyridine (TpmPy, (1)) and 4-((tris-2,2,2-(3-phenylpyrazol-1-yl)ethoxy)methyl)pyridine (TpmPy(Ph), (2)) have been synthesized and their coordination behavior toward Fe(II), Ni(II), Zn(II), Cu(II), Pd(II), and V(III) centers has been studied. Reaction of (1) with Fe(BF(4))(2) x 6 H(2)O yields [Fe(TpmPy)(2)](BF(4))(2) (3), that, in the solid state, shows the sandwich structure with trihapto ligand coordination via the pyrazolyl arms, and is completely low spin (LS) until 400 K. Reactions of 2 equiv of (1) or (2) with Zn(II) or Ni(II) chlorides give the corresponding metal complexes with general formula [MCl(2)(TpmPy*)(2)] (M = Zn, Ni; TpmPy* = TpmPy, TpmPy(Ph)) (4-7) where the ligand is able to coordinate through either the pyrazolyl rings (in case of [Ni(TpmPy)(2)]Cl(2) (5)) or the pyridyl-side (for [ZnCl(2)(TpmPy)(2)] (4), [ZnCl(2)(TpmPy(Ph))(2)] (6) and [NiCl(2)(TpmPy(Ph))(2)] (7)). The reaction of (1) with VCl(3) gives [VOCl(2)(TpmPy)] (8) that shows the N(3)-pyrazolyl coordination-mode. Moreover, (1) and (2) react with cis-[PdCl(2)(CH(3)CN)(2)] to give the disubstituted complexes [PdCl(2)(TpmPy)(2)] (9) and [PdCl(2)(TpmPy(Ph))(2)] (10), respectively, bearing the scorpionate coordinated via the pyridyl group. Compounds (9) and (10) react with Fe(BF(4))(2) to give the heterobimetallic Pd/Fe systems [PdCl(2)(mu-TpmPy)(2)Fe](BF(4))(2) (11) and [PdCl(2)(mu-TpmPy(Ph))(2)Fe(2)(H(2)O)(6)](BF(4))(4) (13), respectively. Compound (11) can also be formed from reaction of (3) with cis-[PdCl(2)(CH(3)CN)(2)], while reaction of (3) with Cu(NO(3))(2) x 2.5 H(2)O generates [Fe(mu-TpmPy)(2)Cu(NO(3))(2)](BF(4))(2) (12), confirming the multidentate ability of the new chelating ligands. The X-ray diffraction analyses of compounds (1), (3), (4), (5), and (9) are also reported.

V(IV), Fe(II), Ni(II) and Cu(II) complexes bearing 2,2,2-tris(pyrazol-1-yl)ethyl methanesulfonate: application as catalysts for the cyclooctane oxidation

Water-soluble compounds [VOCl2{CH3SO2OCH2C(pz)3}] (pz = pyrazol-1-yl) 1, [FeCl2{CH3SO2OCH2C(pz)3}] 2, [NiCl2{CH3SO2OCH2C(pz)3}] 3 and [Cu{CH3SO2OCH2C(pz)3}2](OTf)24 were obtained by reactions between the corresponding metal salts and 2,2,2-tris(pyrazol-1-yl)ethyl methanesulfonate, CH3SO2OCH2C(pz)3. They were isolated as air-stable solids and fully characterized by IR, FTIR, NMR (for 2), EPR (for 1), ESI-MS(+/−), elemental analysis and (for 4) single-crystal X-ray diffraction. In all, half- (1–3) or full-sandwich (4), compounds the C-scorpionate ligand shows the N,N,N-coordination mode. 3 and 4 appear to provide the first examples of a Ni(II) and a full-sandwich Cu(II) compound respectively, bearing that scorpionate ligand. Compound 3 is the first Ni(II) tris(pyrazol-1-yl)methane type complex to be applied as catalyst for the oxidation of alkanes. Compounds 1–4 exhibit catalytic activity for the peroxidative (with aq. H2O2) oxidation, in water/acetonitrile medium and under mild homogeneous conditions, of cyclooctane to the corresponding alcohol and ketone (yields up to ca. 27%). The effect of the presence of additives, such as nitric acid or pyridine, was studied.

Effects of gamma radiation on wastewater microbiota

Wastewater treatment by gamma radiation is a promising technology, with the capacity to reduce the impact of chemical and biological pollution of effluents in the environment. The aim of this study was to find out the effect of gamma radiation on the inactivation response of wastewater microorganisms. Wastewater samples were irradiated at a Co-60 facility, at different dose rates and at sublethal doses. The D10-values of total coliforms and mesophilic microbiota were determined for each sample and dose rate. Radio-resistant microorganisms in wastewater samples were isolated and their growth and inactivation kinetics in different composition substrates were determined, to find out the capacity of these bacteria to biodegrade the organic content of the wastewater. The results obtained suggest that irradiation substrate and dose rate influence the response of microorganisms to gamma radiation and could be also important factors for bioremediation.

Mathematical Modeling of Atherosclerotic Plaque Formation Coupled with a Non-Newtonian Model of Blood Flow

We deal with a mathematical model of atherosclerosis plaque formation, which describes the early formation of atherosclerotic lesions. The model assumes that the inflammatory process starts with the penetration of low-density lipoproteins cholesterol in the intima, and that penetration will occur in the area of lower shear stress. Using a system of reaction-diffusion equations, we first provide a one-dimensional model of lesion growth. Then we perform numerical simulations on an idealized two-dimensional geometry of the carotid artery bifurcation before and after the formation of the atherosclerotic plaque. For that purpose, we consider the blood as an incompressible non-Newtonian fluid with shear-thinning viscosity. We also present a study of the wall shear stress and blood velocity behavior in a geometry with one plaque and also with two plaques in different positions.

Mathematical Analysis and Numerical Simulations for a Model of Atherosclerosis

Atherosclerosis is a chronic inflammatory disease that occurs mainly in large and medium-sized elastic and muscular arteries. This pathology is essentially caused by the high concentration of low-density-lipoprotein (LDL) in the blood. It can lead to coronary heart disease and stroke, which are the cause of around 17.3 million deaths per year in the world. Mathematical modeling and numerical simulations are important tools for a better understanding of atherosclerosis and subsequent development of more effective treatment and prevention strategies. The atherosclerosis inflammatory process can be described by a model consisting of a system of three reaction-diffusion equations (representing the concentrations of oxidized LDL, macrophages and cytokines inside the arterial wall) with non-linear Neumann boundary conditions. In this work we prove the existence, uniqueness and boundedness of global solutions, using the monotone iterative method. Numerical simulations are performed in a rectangle representing the intima, to illustrate the mathematical results and the atherosclerosis inflammatory process.

Evaluation of potential of gamma radiation as a conservation treatment for blackberry fruits

BACKGROUND: Blackberries consumption has been associated with health benefits. However, these fruits present a short shelflife. Thus, food irradiation is a potential alternative technology for conservation of these fruits without use of chemicals. OBJECTIVE: Analyse the potentiality of gamma radiation as a decontamination method for blackberry fruits. METHODS: Fresh packed blackberries were irradiated in a Co-60 source at two doses (1.0 and 1.5 kGy). Bioburden, physical and rheological, sensorial and total soluble content parameters were assessed before irradiation, immediately after and at two days storage time at 4 ◦ C. RESULTS: The characterization of blackberries microbiota point out to an average bioburden value of 10 4 CFU/g and to a microbial population predominantly composed by filamentous fungi. The inactivation studies on the blackberries mesophilic population indicated a limited microbial inactivation (<1 log decimal reduction) for the applied radiation doses, being the surviving population mainly constituted by filamentous fungi and yeast. No effect of irradiation on colour of blackberries was observed. Concerning texture parameters, no significant differences were observed in both fracturability and firmness between non-irradiated and irradiated blackberries immediately after irradiation. In blackberries stored for two days, both parameters were slightly lower in irradiated blackberries, compared to non-irradiated blackberries. The performed sensorial analysis indicated a similar acceptability among irradiated and non-irradiated fruits. CONCLUSION: This work reveals gamma irradiation treatment potential since no major impact was detected on blackberries physical, rheological and sensory attributes. Further studies with longer periods of storage are needed to elucidate the advantages of irradiation as a conservation treatment.