Synthesis,Pharmacological Evaluation,and Docking Studies of Novel Pyridazinone‐Based Cannabinoid Receptor Type 2 Ligands

In recent years, cannabinoid type 2 receptors (CB₂R) have emerged as promising therapeutic targets in a wide variety of diseases. Selective ligands of CB₂R are devoid of the psychoactive effects typically observed for CB₁R ligands. Based on our recent studies on a class of pyridazinone 4‐carboxamides, further structural modifications of the pyridazinone core were made to better investigate the structure–activity relationships for this promising scaffold with the aim to develop potent CB₂R ligands. In binding assays, two of the new synthesized compounds [6‐(3,4‐dichlorophenyl)‐2‐(4‐fluorobenzyl)‐cis‐N‐(4‐methylcyclohexyl)‐3‐oxo‐2,3‐dihydropyridazine‐4‐carboxamide ( 2 ) and 6‐(4‐chloro‐3‐methylphenyl)‐cis‐N‐(4‐methylcyclohexyl)‐3‐oxo‐2‐pentyl‐2,3‐dihydropyridazine‐4‐carboxamide ( 22 )] showed high CB₂R affinity, with K_i values of 2.1 and 1.6 nm , respectively. In addition, functional assays of these compounds and other new active related derivatives revealed their pharmacological profiles as CB₂R inverse agonists. Compound 22 displayed the highest CB₂R selectivity and potency, presenting a favorable in silico pharmacokinetic profile. Furthermore, a molecular modeling study revealed how 22 produces inverse agonism through blocking the movement of the toggle‐switch residue, W6.48.     

Novel fluorine containing polyfluorenes with efficient blue electroluminescence

The synthesis, structural characterization, photo and electroluminescence, thermal and electrochemical properties of a new fluorinated fluorene-containing copolymer are described. The copolymer is formed by alternating mers of [2,3,5,6 tetrafluoro-1,4 phenylene] and [9,9′-dihexyl-2,7 fluorene] and emits blue light with low turn on voltages. The EL performance of the fluorinated copolymer was superior to those of the non-fluorinated analog copolymer and of the corresponding poly(9,9′dihexyl-2,7 polyfluorene) homopolymer.     

Free-radical scavenging capacity and reducing power of wild edible mushrooms from northeast Portugal: Individual cap and stipe activity

The antioxidant properties of two wild edible mushroom species from the northeast of Portugal, Lactarius deliciosus (L.) Gray and Tricholoma portentosum (Fr.) Quél., were evaluated. Methanolic extracts from the entire mushroom, the cap and the stipe, separately, were screened for their reducing power and free radical scavenging capacity by chemical assays. The total phenolic content was determined, in order to assess its effect on the extract’s antioxidant activity. Both two species showed antioxidant potential; but L. deliciosus proved to be more active. The portion of the mushroom used had an influence on the results obtained, with the cap methanolic extracts exhibiting the greatest antioxidant effect.     

Microbiological characterization of randomly selected Portuguese raw milk cheeses with reference to food safety

Seventy raw milk cheeses made in different regions of Portugal, both hard and soft varieties, made with cow's, ewe's, or goat's milk or combinations of these, were sampled within their quoted shelf lives for microbiological safety. On the basis of the presence or numbers of Escherichia coli, E. coli O157, Staphylococcus aureus, Salmonella, and Listeria monocytogenes, cheeses were categorized as satisfactory, acceptable, unsatisfactory, or unacceptable and potentially hazardous. Twenty-two of the 70 cheeses were classified as satisfactory or acceptable. Thirty-seven of the cheeses were considered unsatisfactory because of the presence of E. coli, S. aureus, or both, while 11 of the cheeses were graded as unacceptable and potentially hazardous because of the presence of excessive numbers of S. aureus, E. coli, or L. monocytogenes and the presence of Salmonella in three of these. All cheeses graded as unacceptable and potentially hazardous were soft or semisoft cheeses made with ewe's and goat's milk, with the exception of two hard cheeses made with cow's milk. E. coli O157 was not detected in any of the cheeses. According to the present results, it seems that the presence or counts of pathogenic or indicator organisms in raw milk cheeses cannot be related to the processing conditions, milk type, or region of production.     

Schrifttumsberichte

Ohne Zusammenfassung     

Design and development of two-dimensional position sensitive photo-detector

Position sensitive photo-detectors (PSDs) utilize the lateral photovoltaic effect to produce an electrical output that varies linearly with the position of a light spot incident on a semiconductor junction. Design, fabrication and characterization of newly developed silicon PSD, which employ the planar technology and double ion implantation with different doses, are described. Shallow and low-doped p-n junction is formed by boron implantation in n-type silicon substrate. The position characteristics of PSD are symmetric to the zero and linear in the 80% of the active area. For a higher resistivity top layer (lower implanted dose), the sensitivity grows up and the linearity gets improved. The influence of the substrate is not substantial for the position characteristics. The response of the sensor, measured by pulsed 15 ns laser, was determined to be about 100 ns. Described PSD has been used in the construction of simple light spot rotational follower.     

Recyclable,Flexible, Low‐Power Oxide Electronics

The ability to process and dimensionally scale field‐effect transistors with and on paper and to integrate them as a core component for low‐power‐consumption analog and digital circuits is demonstrated. Low‐temperature‐processed p‐ and n‐channel integrated oxide thin‐film transistors in the complementary metal oxide semiconductor (CMOS) inverter architecture are seamlessly layered on mechanically flexible, low‐cost, recyclable paper substrates. The possibility of building these circuits using low‐temperature processes opens the door to new applications ranging from smart labels and sensors on clothing and packaging to electronic displays printed on paper pages for use in newspapers, magazines, books, signs, and advertising billboards. Because the CMOS circuits reported constitute fundamental building blocks for analog and digital electronics, this development creates the potential to have flexible form factor computers seamlessly layered onto paper. The holistic approach of merging low‐power circuitry with a recyclable substrate is an important step towards greener electronics.     

Synthesis of polar vinyl monomer–olefin copolymers by α‐diimine nickel catalyst

Vinyl acetate, methyl methacrylate, acrylonitrile and methyl vinyl ketone were investigated for co‐ and terpolymerization with ethylene and ethylene–propylene. Precursor [bis(N,N ′‐dimesitylimino)acenaphthene]dibromonickel, activated by methylaluminoxane was used as a catalyst system and trialkylaluminium was employed to block the polar groups for these polymerizations. Polymerization activities of the order of magnitude of 10⁶ in the case of vinyl acetate and methyl methacrylate, and 10⁵ in the case of acrylonitrile were achieved. Microanalysis and GPC of acrylonitrile copolymers found about 17 units of acrylonitrile per polymer chain. Copolymers with very different properties from the parent homopolymers were obtained in all cases except that of methyl vinyl ketone. © 2001 Society of Chemical Industry     

A new contribution to the study of the electrosynthesis of magnetic nanoparticles: the influence of the supporting electrolyte

This paper shows how magnetic nanoparticles are produced by electrochemical synthesis using a low carbon steel bar as an anode and 100 mA cm^?2 electric perturbations at room temperature. Two different kinds of salts, (CH₃)₄NCl and NaCl, were used to prepare the supporting electrolyte solutions. This allowed a comparison to be made between a surfactant and common salt, and allowed their influence on particle size to be analyzed. Additionally, mixtures of water and ethanol were added to the electrolyte solution in order to improve particle size distribution. The nanoparticle samples were characterized by X-ray diffraction, TEM, magnetization measurements, and Raman and Mössbauer spectroscopy. The results showed that after an optimized time of 10 min, the nanoparticles obtained in all the evaluated electrolytes were mainly magnetite (Fe₃O₄). The particles were between 8 and 10 nm in size. Depending on the nature of the electrolyte, the magnetite nanoparticles exhibited high purity and stoichiometry. The presence of ethanol in the electrolyte avoided particle agglomeration during the formation of magnetite. When the magnetic nanoparticles were exposed to an external magnetic field they showed superparamagnetic behavior and negligible coercivity. Such qualities are extremely useful for applications like ferrofluid precursors.