Bicyclische Oxalamidine – Bausteine für hochsubstituierte 2,2′-Bipyridine und Benzolderivate

Bicyclic Oxalic Amidines as Building Blocks for Highly Substituted 2,2′-Bipyridines and Benzene Derivatives The bis-imidoylchlorides 1 derived from oxalic acid exhibit a high regio- and chemoselectivity. As in the case of 2-picolylamine 2 the acylation with oxalyl chloride furnished the expected open chained oxalic diamides 3a while the imidoylchlorides 1 yield exclusively the new pyrido[1,2-a]-pyrazines 4 . These heterocycles represent readily crystallisable and orange-red coloured compounds with a mesomeric dipolar aromatic substructure. The synthetic value of 4 is based on their easy transformation into highly substituted arenes and hetarenes. Thus, electron deficient dienophiles as dimethyl acetylenedicarboxylate lead to the bipyridines 6 via Hetero-Diels-Alder-Reaction and subsequent 1,5-hydrogen shift. In a complex reaction the derivatives of maleic acid 7a – c yield the bipyridines of type 9 while the new hexasubstituted arenes 10 can be isolated under anaerobic conditions and with an excess of dienophilic component. A x-ray structural determination of 10b shows an alternation of bond lenghts in the benzene ring. This can be considered as a distinct disturbance of aromaticity caused by the arrangement of substituents.     

The diastereofacial selectivity of the addition of various 1-metalated 1-heptynes to substituted cyclopentanecarbaldehydes. – The use of 1-titanated 1-heptyne for the construction of the alkyl side chain of Prostaglandins

A highly diastereoselective addition of 1-heptyne to substituted cyclopentanecarbaldehydes is one of the indispensable prerequisites to the construction of the (S)-3-hydroxy-1(E)-octenyl side chain of prostaglandins by palladium(II)-catalyzed [3,3]-sigmatropic rearrangement of allylic acetates. It was found that 1-titanated 1-heptynes afford the Cram product at best with a diastereofacial selectivity of 92.5%. The corresponding lithium and magnesium compounds are less diastereoselective.     

Airway Delivery of Hydrogel-Encapsulated Niclosamide for the Treatment of Inflammatory Airway Disease

Repurposing of the anthelminthic drug niclosamide was proposed as an effective treatment for inflammatory airway diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Niclosamide may also be effective for the treatment of viral respiratory infections, such as SARS-CoV-2, respiratory syncytial virus, and influenza. While systemic application of niclosamide may lead to unwanted side effects, local administration via aerosol may circumvent these problems, particularly when the drug is encapsulated into small polyethylene glycol (PEG) hydrospheres. In the present study, we examined whether PEG-encapsulated niclosamide inhibits the production of mucus and affects the pro-inflammatory mediator CLCA1 in mouse airways in vivo, while effects on mucociliary clearance were assessed in excised mouse tracheas. The potential of encapsulated niclosamide to inhibit TMEM16A whole-cell Cl⁻ currents and intracellular Ca²⁺ signalling was assessed in airway epithelial cells in vitro. We achieved encapsulation of niclosamide in PEG-microspheres and PEG-nanospheres (Niclo-spheres). When applied to asthmatic mice via intratracheal instillation, Niclo-spheres strongly attenuated overproduction of mucus, inhibited secretion of the major proinflammatory mediator CLCA1, and improved mucociliary clearance in tracheas ex vivo. These effects were comparable for niclosamide encapsulated in PEG-nanospheres and PEG-microspheres. Niclo-spheres inhibited the Ca²⁺ activated Cl⁻ channel TMEM16A and attenuated mucus production in CFBE and Calu-3 human airway epithelial cells. Both inhibitory effects were explained by a pronounced inhibition of intracellular Ca²⁺ signals. The data indicate that poorly dissolvable compounds such as niclosamide can be encapsulated in PEG-microspheres/nanospheres and deposited locally on the airway epithelium as encapsulated drugs, which may be advantageous over systemic application.     

Extraction of heavy metals from soils using biodegradable chelating agents

Metal pollution of soils is widespread across the globe, and the clean up of these soils is a difficulttask. One possible remediation technique is ex-situ soil washing using chelating agents. Ethylenediaminetetraacetic acid (EDTA) is a very effective chelating agent for this purpose but has the disadvantage that it is quite persistent in the environment due to its low biodegradability. The aim of our work was to investigate the biodegradable chelating agents [S,S]-ethylenediaminedisuccinic acid (EDDS), iminodisuccinic acid (IDSA), methylglycine diacetic acid (MGDA), and nitrilotriacetic acid (NTA) as potential alternatives and compare them with EDTA for effectiveness. Kinetic experiments showed for all metals and soils that 24 h was the optimum extraction time. Longer times only gave minor additional benefits for heavy metal extraction but an unwanted increase in iron mobilization. For Cu at pH 7, the order of the extraction efficiency for equimolar ratios of chelating agent to metal was EDDS > NTA> IDSA > MGDA > EDTA and for Zn it was NTA > EDDS > EDTA >MGDA > IDSA. The comparatively low efficiency of EDTA resulted from competition between the heavy metals and co-extracted Ca. For Pb the order of extraction was EDTA > NTA >EDDS due to the much stronger complexation of Pb by EDTA compared to EDDS. At higher concentration of complexing agent, less difference between the agents was found and less pH dependence. There was an increase in heavy metal extraction with decreasing pH, but this was offset by an increase in Ca and Fe extraction. In sequential extractions EDDS extracted metals almost exclusively from the exchangeable, mobile, and Mn-oxide fractions. We conclude that the extraction with EDDS at pH 7 showed the best compromise between extraction efficiency for Cu, Zn, and Pb and loss of Ca and Fe from the soil.     

Scrubbing carbon dioxide prevents overestimation of insect mortality in long-duration static phosphine toxicity assays

Exposing insects to toxicants such as phosphine (PH₃) in sealed chambers is a common procedure in fumigant efficacy testing. During long exposures, carbon dioxide (CO₂) produced by metabolic processes of fed insects may accumulate in the vessel. As CO₂ enhances the toxicity of several fumigants, concomitant exposure of fumigant and CO₂ may lead to erroneous measurements of insect mortality and thus fumigant toxicity. In this study, the effect of a CO₂ scrubber such as soda lime (a solid formulation of wet hydroxides of calcium, sodium and potassium) or periodic flushing of the headspace, on insect mortality in static PH₃ toxicity assays was compared with an “unscrubbed” (no intervention) treatment. Soda lime was highly effective in removing CO₂ from the headspace of sealed chambers, without measurable loss of PH₃. Mortality of Sitophilus oryzae (L.) adults treated with phosphine in chambers scrubbed with soda lime or flushed (opened) daily was considerably lower than in unscrubbed chambers. Twenty grams of soda lime per litre of exposure chamber is recommended to obtain accurate static fumigant mortality results.     

Sustainability of biofuels in Latin America: Risks and opportunities

Several Latin American countries are setting up biofuel programmes to establish alternative markets for agricultural commodities. This is mainly triggered by the current success of Brazilian bioethanol production for the domestic market and for export. Furthermore, the global biofuel market is expected to increase due to ambitious biofuel programmes in the EU and in the USA. Colombia, Venezuela, Costa Rica and Guatemala are focusing on bioethanol production from sugarcane whereas biofuel production in Argentina is based on soy biodiesel. Recent developments of the biofuel sector take place extremely rapid especially in Argentina, which became one of the five largest biodiesel producers in the world in 2008. Till date no specific biofuel sustainability certification systems have been implemented in Latin American, as well as on global level. This fact and the predominant use of food crops for biofuel production raise concerns about the sustainability of biofuel production related to environmental and social aspects. This paper provides an overview of the hotspots of conflicts in biofuel production in Latin America. It investigates presently available sustainability tools and initiatives to ensure sustainable biofuel production in Latin America. Finally, it provides an outlook on how to integrate sustainability in the Latin American biofuel sector.     

Progress in the Synthesis of Nanocrystalline BaTiO3 Powders for MLCC

Future improvements in the development of highly volume-efficient multilayer ceramic capacitors (MLCC) require manufacturing processes that allow for a reduced dielectric thickness well below 1 μm. Obviously, such thin dielectric layers can only be produced if nanosized dielectric powders are applied and deposited by techniques more advanced than tape casting and screen printing. These processes require high-purity, homogeneous, weakly agglomerated ultrafine powders. Over the past few years, significant progress has been made in the synthesis of nanocrystalline BaTiO₃-based powders for use in MLCC. The present review article aims to summarize the present state of the art with respect to some of the technically and industrially most relevant preparation routes, including methods based on solid-state reactions and, more importantly, solution-based approaches.     

21世纪城市设计和开放空间规划中的浪漫主义精神

人类文明发展史上每一次价值观的改变,都会引起新的城市设计和开放空间规划思想和手法的产生.1 8世纪浪漫主义思想的产生,是文化思想发展史上一次重要的转折,它对同时期的景观设计领域,也产生了重要的影响.以往的园林,代表的是内部实体与外在形式创造性的统一,而21世纪的景观设计语言,必须为人与人之间或人与自然之间的相互关系,提供现实主义层面的反映.浪漫主义,是对应于21世纪人类价值观的设计思想和手法的一个探索性回答.     

Expression of SLC26A9 in Airways and Its Potential Role in Asthma

SLC26A9 is an epithelial anion transporter with a poorly defined function in airways. It is assumed to contribute to airway chloride secretion and airway surface hydration. However, immunohistochemistry showing precise localization of SLC26A9 in airways is missing. Some studies report localization near tight junctions, which is difficult to reconcile with a chloride secretory function of SLC26A9. We therefore performed immunocytochemistry of SLC26A9 in sections of human and porcine lungs. Obvious apical localization of SLC26A9 was detected in human and porcine superficial airway epithelia, whereas submucosal glands did not express SLC26A9. The anion transporter was located exclusively in ciliated epithelial cells. Highly differentiated BCi-NS1 human airway epithelial cells grown on permeable supports also expressed SLC26A9 in the apical membrane of ciliated epithelial cells. BCi-NS1 cells expressed the major Cl⁻ transporting proteins CFTR, TMEM16A and SLC26A9 in about equal proportions and produced short-circuit currents activated by increases in intracellular cAMP or Ca²⁺. Both CFTR and SLC26A9 contribute to basal chloride currents in non-stimulated BCi-NS1 airway epithelia, with CFTR being the dominating Cl⁻ conductance. In wtCFTR-expressing CFBE human airway epithelial cells, SLC26A9 was partially located in the plasma membrane, whereas CFBE cells expressing F508del-CFTR showed exclusive cytosolic localization of SLC26A9. Membrane localization of SLC26A9 and basal chloride currents were augmented by interleukin 13 in wild-type CFTR-expressing cells, but not in cells expressing the most common disease-causing mutant F508del-CFTR. The data suggest an upregulation of SLC26A9-dependent chloride secretion in asthma, but not in the presence of F508del-CFTR.