The Fe2+-mediated decomposition, PfATP6 binding, and antimalarial activities of artemisone and other artemisinins: the unlikelihood of C-centered radicals as bioactive intermediates

The results of Fe(2+)-induced decomposition of the clinically used artemisinins, artemisone, other aminoartemisinins, 10-deoxoartemisinin, and the 4-fluorophenyl derivative have been compared with their antimalarial activities and their ability to inhibit the parasite SERCA PfATP6. The clinical artemisinins and artemisone decompose under aqueous conditions to give mixtures of C radical marker products, carbonyl compounds, and reduction products. The 4-fluorophenyl derivative and aminoartemisinins tend to be inert to aqueous iron(II) sulfate and anhydrous iron(II) acetate. Anhydrous iron(II) bromide enhances formation of the carbonyl compounds and provides a deoxyglycal from DHA and enamines from the aminoartemisinins. Ascorbic acid (AA) accelerates the aqueous Fe(2+)-mediated decompositions, but does not alter product distribution. 4-Oxo-TEMPO intercepts C radicals from a mixture of an antimalaria-active trioxolane, 10-deoxoartemisinin, and anhydrous iron(II) acetate to give trapped products in 73 % yield from the trioxolane, and 3 % from the artemisinin. Artemisone provides a trapped product in 10 % yield. Thus, in line with its structural rigidity, only the trioxolane provides a C radical eminently suited for intermolecular trapping. In contrast, the structural flexibility of the C radicals from the artemisinins allows facile extrusion of Fe(2+) and collapse to benign isomerization products. The propensity towards the formation of radical marker products and intermolecular radical trapping have no relationship with the in vitro antimalarial activities of the artemisinins and trioxolane. Desferrioxamine (DFO) attenuates inhibition of PfATP6 by, and antagonizes antimalarial activity of, the aqueous Fe(2+)-susceptible artemisinins, but has no overt effect on the aqueous Fe(2+)-inert artemisinins. It is concluded that the C radicals cannot be responsible for antimalarial activity and that the Fe(2+)-susceptible artemisinins may be competitively decomposed in aqueous extra- and intracellular compartments by labile Fe(2+), resulting in some attenuation of their antimalarial activities. Interpretations of the roles of DFO and AA in modulating antimalarial activities of the artemisinins, and a comparison with antimalarial properties of simple hydroperoxides and their behavior towards thapsigargin-sensitive SERCA ATPases are presented. The general basis for the exceptional antimalarial activities of artemisinins in relation to the intrinsic activity of the peroxide within the uniquely stressed environment of the malaria parasite is thereby adumbrated.     

Immobilization of TiO2 into Self‐Supporting Photocatalytic Foam: Influence of Calcination Temperature

Immobilization of photocatalytic powder is crucial to obtain industrially relevant purification processes. To achieve this goal, self‐supporting TiO₂ foams were manufactured by a polyacrylamide gel process. These gels were calcined at different temperatures to study the effect of the calcination temperature on foam characteristics (rigidity, crystallinity, and porosity) and its influence on photocatalytic activity. The results show that an optimal degradation is achieved for those foams calcined between 700 and 800°C. Calcination at higher temperatures results in a steep decrease in activity, explained by stability issues of the material due to formation of Na₂SO₄ phases and a larger rutile fraction.     

The surface energy of palygorskite

An average value for the surface energy (γ¯_S) of palygorskite was determined from experimental data of spreading pressure, the surface tension of water and its contact angle using a formula based on the combination of the Young equation with a general equation of pair interaction. The value found is 226.6 mJ m^− 2. Some factors that affect the determination of surface energy via solid-liquid interaction are exposed. The backgrounds of previous formulas for the calculation of the surface energy of palygorskite are also critically examined.     

Voltammetric detection of the interactions between RNO2 and electron acceptors in aqueous medium at highly boron doped diamond electrode (HBDDE)

This paper describes the electrochemical behavior of the nitrofurazone (NFZ), in predominantly aqueous medium, in the absence and presence of glutathione (reduced form) (GSH), l-cysteine (Cys) and O₂ using a highly boron doped diamond electrode (HBDDE). In presence of [Thiol] ≥ 3.7 × 10⁻² mol L⁻¹ NFZ is directly reduced to RNO-Thiol adducts in an electrochemical process involving two electrons and two protons. On the other side, O₂ acts as a RNO₂^•− scavenger and the velocity constant for the reaction, kO₂, is 60 L mol⁻¹ s⁻¹. The process is catalytic and can be used to the analytical determination of NFZ in the range of 9.9 × 10⁻⁷ ≤ [NFZ] ≤ 1.1 × 10⁻⁵ mol L⁻¹ at pH 8.0, with sensitivity of 2.2 × 10⁶ μA mol⁻¹ cm⁻² and detection limit of 3.4 × 10⁻⁷ mol L⁻¹. The analytical parameters were similar to those obtained at pH 4.0 using the direct reduction of NFZ to the respective amine derivative in a process involving six electrons and six protons. The characterization of NFZ global reduction process in aqueous medium and at relative low scan rate, 100 mV s⁻¹, was only possible due the intrinsic superficial characteristics of the HBDDE, which stabilize the RNO₂⁻ free radical, allowing to work in a large potential window, without losing the RNO₂⁻ oxidation signal.     

Effect of hydroxyl content on the morphology and properties of epoxy/poly(styrene-co-allylalcohol) blends

Blends based on epoxy resin and random copolymers, poly(styrene-co-allylalcohol) (PS-co-PA), were studied. Two PS-co-PA copolymers, with different hydroxyl content, and a polyallylalcohol (PA) homopolymer were used to analyze the effect of polyalcohol content. The polymers presented similar values of molar mass. The miscibility of noncured mixtures and the thermal transition behavior of cured blends were investigated by differential scanning calorimetry (DSC) and dynamic mechanical thermal analysis (DMTA). Its morphology was studied using both scanning and transmission electron microscopy (SEM and TEM). While the epoxy/PA blends are homogenous materials, because of the epoxy/hydroxyl reaction, PS-co-PA/epoxy blends shows separated phases. In these blends, the presence of a third glass transition, whose value is an intermediate between those of pure components, and the presence of a well-defined interfacial layer between PS-co-PA domains and epoxy matrix indicates a secondary epoxy/hydroxyl reaction. The modification of epoxy resin with PS-co-PA provides significant increase in the storage modulus measured by DMTA. POLYM. ENG. SCI., 47:1580–1588, 2007. © 2007 Society of Plastics Engineers     

A white emitting poly(phenylenevinylene)

A white emitting copolymer with the polyphenylenevinylene (PPV) structure is obtained via the Stille cross-coupling reaction. Substitution of hydrogen atoms with fluorine atoms on the vinylene units of poly(1,4-dialkoxyphenylenevinylene) shifts the emission from orange-red to blue. White emission is obtained by combining dialkoxyphenylenedifluorovinylene and dialkoxyphenylenevinylene units in proper ratio. The two complementary emitters are obtained separately by Stille polymerization reaction. Then, the two reaction mixtures are combined without purification in different ratios and further reacted in similar experimental conditions. A white luminescent material is obtained using 99/1 mixing ratio. OLED devices fabricated with this copolymer shows near-white emission with CIE (0.30, 0.40) and excellent stability in the range 10–200 cd/m².     

3-dimensional microscope analysis of bone and tooth surface modifications: comparisons of fossil specimens and replicas

Cut-marks on fossil bones and teeth are an important source of evidence in the reconstruction of ancient butchery practices. The analysis of butchery marks has allowed archaeologists to interpret aspects of past subsistence strategies and the behavior of early humans. Recent advances in optical scanning microscopy allow detailed measurements of cut-mark morphology to be undertaken. An example of this technology is the Alicona 3D InfiniteFocus imaging microscope, which has been applied recently to the study of surface modifications on bones and teeth. Three-dimensional models generated by the Alicona microscope have been used to identify cross-sectional features of experimental cut-marks that are characteristic for specific cutting actions (e.g., slicing, chopping, scraping) and different tool types (e.g., metal versus stone tools). More recently, this technology has been applied successfully to the analysis of ～500,000 year-old cut-marked animal bones from Boxgrove (U.K.), as well as cannibalized 14,700 cal BP year-old human bones from Gough's Cave (U.K.). This article describes molding methods used to replicate fragile prehistoric bones and teeth, where image quality was adversely affected by specimen translucency and reflectivity. Alicona images generated from molds and casts are often of better quality than those of the original specimen.     

Structure and secretory activity of cultured chondrocytes from patients with osteoarthritis.

Cartilage samples were taken from OA patients in order to describe and quantify pro-inflammatory mediators. Samples were cultured under aseptic conditions in Dulbecco's modified Eagle medium at 37 degrees C for 10 days. Control samples, taken from non-inflammatory cartilage, were cultured under the same conditions. The levels of NO(-)2 and NO(-)3 were measured in the supernatant using a spectrophotometric assay. The activity of MMP-1 was quantified by ELISA. The concentration of NO(-)x was 47.3 +/- 4.1 microM in the OA cartilague and 10.7 +/- 1.8 microM in the controls. The average MMP-1 activity was 3,650 +/- 387 ng/ml in the OA cartilage and 2,150 +/- 190 ng/ml in the control samples. These increased values of MMP-1 and NO(-)x observed in the OA cartilage suggest a higher catabolic activity. A morphological analysis of OA chondral tissue using light microscopy shows that the surface of the tissue is characterized by the presence of aggregated chondrocytes or "clones" but in the deeper areas isolated cells are found. These results could be a significant contribution towards the identification of biological markers indicating the presence of OA activity.     

Indoor air quality in schools of a highly polluted south Mediterranean area

This study aimed at surveying lower secondary schools in southern Italy, in a highly polluted area. A community close to an industrial area and three villages in rural areas was investigated. Indoor temperature, relative humidity (RH), gaseous pollutants (CO₂ and NO₂), selected biological pollutants in indoor dust, and the indoor/outdoor mass concentration and elemental composition of PM_2.5 were ascertained. Temperature and RH were within, or close to, the comfort range, while CO₂ frequently exceeded the threshold of 1000 ppm, indicating inadequate air exchange rate. In all the classrooms, median NO₂ levels were above the WHO threshold value. Dermatophagoides p. allergen concentration was below the sensitizing threshold, while high endotoxin levels were detected in the classrooms, suggesting schools may produce significant risks of endotoxin exposure. Concentration and solubility of PM_2.5 elements were used to identify the sources of indoor particles. Indoor concentration of most elements was higher than outdoors. Resuspension was responsible for the indoor increase in soil components. For elements from industrial emission (Cd, Co, Ni, Pb, Sb, Tl, V), the indoor concentration depended on penetration from the outside. For these elements, differences in rural vs industrial concentrations were found, suggesting industrial sources may influence indoor air quality nearby schools.