Synthesis and biological evaluation of pyrazolylnaphthoquinones as new potential antiprotozoal and cytotoxic agents

The importance of American trypanosomiasis (Chagas' disease) in human pathology is widely known. The prognosis of this disease is poor and the choice of effective medicines limited, thus study of new drugs is absolutely necessary. In this work, the activities of three new pyrazolylnaphthoquinones, heterocyclic naphthoquinones bearing 3-aminopyrazole rings, were evaluated on Trypanosoma cruzi, the etiological agent of Chagas' disease. These activities were compared with those of three 5-aminoisoxazole analogues. In addition, since these compounds belong to a family of antiprotozoal and cytotoxic/antitumor agents, the activities of all six against Plasmodium falciparum, Trypanosoma brucei rhodesiense, and murine L-6 cells were also investigated. In the biological tests, five of the compounds showed significant in vitro trypanocidal activities against T. cruzi, with activities similar to that of benznidazole. Two of the 5-aminoisoxazole analogues also showed good activities, in one case highly selective, against the K1 and NF54 strains of P. falciparum (IC(50)<0.12 microg mL(-1)). Three of the compounds were cytotoxic to murine L-6 cells (IC(50)=0.21-0.50 microg mL(-1)). The results suggested that the three pyrazolylnaphthoquinones and one of the 5-aminoisoxazole analogues could be starting points for lead optimization programs against T. cruzi and P. falciparum, respectively.     

Lipid peroxidation during n−3 fatty acid and vitamin E supplementation in humans

The purpose of this study was to investigate in healthy humans the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake, alone or in combination with dL-α-tocopherol acetate (vitamin E) supplements on lipid peroxidation. Eightly men were randomly assigned in a double-blind fashion to take daily for 6 wk either menhaden oil (6.26 g, n−3 fatty acids) or olive oil supplements with either vitamin E (900 IU) or its placebo. Antioxidant vitamins, phospholipid composition, malondialdehyde (MDA), and lipid peroxides were measured in the plasma at baseline and week 6. At the same time, breath alkane output was measured. Plasma α-tocopherol concentration increased in those receiving vitamin E (P<0.0001). In those supplemented with n−3 fatty acids, EPA and DHA increased in plasma phospholipids (P<0.0001) and plasma MDA and lipid peroxides increased (P<0.001 and P<0.05, respectively). Breath alkane output did not change significantly and vitamin E intake did not prevent the increase in lipid peroxidation during menhaden oil supplementation. The results demonstrate that supplementing the diet with n−3 fatty acids resulted in an increase in lipid peroxidation, as measured by plasma MDA release and lipid peroxide products, which was not suppressed by vitamin E supplementation.     

Flame-made Alumina Supported Pd–Pt Nanoparticles: Structural Properties and Catalytic Behavior in Methane Combustion

Bimetallic palladium–platinum nanoparticles supported on alumina were prepared by flame spray pyrolysis. The as-prepared materials were characterized by scanning transmission electron microscopy (STEM), CO chemisorption, nitrogen adsorption (BET), X-ray diffraction (XRD), temperature programmed reduction (TPR), thermogravimetric analysis (TGA) and extended X-ray absorption fine structure (EXAFS) spectroscopy. The materials were tested for the catalytic combustion of methane with a focus on the thermal stability of the noble metal particles. After flame synthesis the noble metal components of the materials were predominantly in oxidized state and finely dispersed on the alumina matrix. Reduction afforded small bimetallic Pd–Pt alloy particles (< 5 nm) supported on Al₂O₃ ceramic nanoparticles. The addition of small amounts of platinum made the palladium particles more resistant against sintering at high temperatures and further lowered the deactivation observed during methane combustion.     

Synthesis and biological evaluation of phosphate prodrugs of 4-phospho-D-erythronohydroxamic acid, an inhibitor of 6-phosphogluconate dehydrogenase

We have previously reported the discovery of potent and selective inhibitors of 6-phosphogluconate dehydrogenase, the third enzyme of the phosphate pentose pathway, from Trypanosoma brucei, the causative organism of human African trypanosomiasis. These inhibitors were charged phosphate derivatives with restricted capacity to enter cells. Herein, we report the synthesis of five different classes of prodrugs: phosphoramidate; bis-S-acyl thioethyl esters (bis-SATE); bis-pivaloxymethyl (bis-POM); CycloSaligenyl; and phenyl, S-acyl thioethyl mixed phosphate esters (mix-SATE). Prodrugs were studied for stability and activity against the intact parasites. Most prodrugs caused inhibition of the growth of the parasites. The activity of the prodrugs against the parasites appeared to be related to their stability in aqueous buffer.     

Decay processes of nitrifying bacteria in biological wastewater treatment systems

A knowledge of the decay rates of autotrophic bacteria is important for reliably modeling nitrification in activated sludge plants. The introduction of nitrite to activated sludge models also requires the separate determination of the kinetics of ammonia- and nitrite-oxidizing bacteria. Batch experiments were carried out in order to study the effects of different oxidiation-reduction potential conditions and membrane separation on the separate decay of these bacteria. It was found that decay is negligible in both cases under anoxic conditions. No significant differences were detected between the membrane and conventional activated sludge. The aerobic decay of these two types of bacteria did not diverge significantly either. However, the measured loss of autotrophic activity was only partly explained by the endogenous respiration concept as incorporated in activated sludge model no. 3 (ASM3). In contrast to nitrite-oxidizing bacteria, ammonia-oxidizing bacteria needed 1-2 h after substrate addition to reach their maximum growth rate measured as a maximum OUR. This pattern could be successfully modeled using the ASM3 extended by enzyme kinetics. The significance of these findings on wastewater treatment is discussed on the basis of the extended ASM3.     

Vibrational spectroscopy of microhydrated conjugate base anions

Conjugate-base anions are ubiquitous in aqueous solution. Understanding the hydration of these anions at the molecular level represents a long-standing goal in chemistry. A molecular-level perspective on ion hydration is also important for understanding the surface speciation and reactivity of aerosols, which are a central component of atmospheric and oceanic chemical cycles. In this Account, as a means of studying conjugate-base anions in water, we describe infrared multiple-photon dissociation spectroscopy on clusters in which the sulfate, nitrate, bicarbonate, and suberate anions are hydrated by a known number of water molecules. This spectral technique, used over the range of 550-1800 cm(-1), serves as a structural probe of these clusters. The experiments follow how the solvent network around the conjugate-base anion evolves, one water molecule at a time. We make structural assignments by comparing the experimental infrared spectra to those obtained from electronic structure calculations. Our results show how changes in anion structure, symmetry, and charge state have a profound effect on the structure of the solvent network. Conversely, they indicate how hydration can markedly affect the structure of the anion core in a microhydrated cluster. Some key results include the following. The first few water molecules bind to the anion terminal oxo groups in a bridging fashion, forming two anion-water hydrogen bonds. Each oxo group can form up to three hydrogen bonds; one structural result, for example, is the highly symmetric, fully coordinated SO(4)(2-)(H(2)O)(6) cluster, which only contains bridging water molecules. Adding more water molecules results in the formation of a solvent network comprising water-water hydrogen bonding in addition to hydrogen bonding to the anion. For the nitrate, bicarbonate, and suberate anions, fewer bridging sites are available, namely, three, two, and one (per carboxylate group), respectively. As a result, an earlier onset of water-water hydrogen bonding is observed. When there are more than three hydrating water molecules (n > 3), the formation of a particularly stable four-membered water ring is observed for hydrated nitrate and bicarbonate clusters. This ring binds in either a side-on (bicarbonate) or top-on (nitrate) fashion. In the case of bicarbonate, additional water molecules then add to this water ring rather than directly to the anion, indicating a preference for surface hydration. In contrast, doubly charged sulfate dianions are internally hydrated and characterized by the closing of the first hydration shell at n = 12. The situation is different for the (-)O(2)C(CH(2))(6)CO(2-) (suberate) dianion, which adapts to the hydration network by changing from a linear to a folded structure at n > 15. This change is driven by the formation of additional solute-solvent hydrogen bonds.     

Lithium Titanate Anode Thin Films for Li‐Ion Solid State Battery Based on Garnets

Solid state electrolytes, such as Li‐Garnets, are fastest Li‐ionic conductor materials that have attracted attention for safe hybrid and full solid state battery architectures. Turning to oxide‐based low voltage anodes gives opportunities to avoid Li‐dendrite formation and also to reach full thin film microbattery architectures based on garnets as high energy density replacement for supercapacitors. Herein, it is demonstrated that Li₄Ti₅O₁₂ thin films deposited by pulsed laser deposition can show stable structures and cycling kinetics reaching almost close to theoretical capacity of 175 mAh g^?1 when combined to Li_6.25Al_0.25La₃Zr₂O₁₂ pellets. Stable operation at room temperature with 90% of theoretical capacity retention at 2.5 mA g^?1 over 22 cycles is achieved on bilayer half cell batteries. Rate capability studies show promising charge and discharge capacities and act as a case study for the well‐known Li₄Ti₅O₁₂ thin film anode, demonstrating its good compatibility with the investigated solid garnet electrolyte. This gives new perspective on the use of oxide‐based low voltage anodes for future strategies avoiding Li‐dendrite formation or safe solid state microbattery thin film assemblies based on Li‐garnets.     

Productivity of Selective Electroenzymatic Reduction and Oxidation Reactions: Theoretical and Practical Considerations

The volumetric productivities, final product concentration and total process times, of electroenzymatic processes comprising reductive electrochemical cofactor regeneration coupled to dehydrogenase or oxygenase catalyzed redox reactions determine process performance. Exemplified for the production of fine chemicals, operational windows were defined to consider these parameters. This theoretical approach allows the identification of limiting process parameters and promising process developments. Several biocatalytic processes for syntheses of specialty chemicals are already in a performance range of technical relevance. Electroenzymology thus evolved to a strong additional technology in the toolbox of biocatalysis and organic chemistry.     

Meßtechnische und rechnerische Untersuchungen an einer mit Vakuum‐Isolations‐Paneelen gedämmten Holztür

Measurement and analytical investigations on wooden door insulated by Vacuum Insulation Panels. Thermal transmittance measurements, IR‐investigations and finite element calculations on a wooden door containing Vacuum Insulation Panels (V.I.P.) were done at EMPA. The results of all these investigations are presented and discussed in this article. The comparison of the different methods and calculations according to the standards shows the differences of the approaches and possible ways for optimization.