NG‐Acylated Aminothiazolylpropylguanidines as Potent and Selective Histamine H2 Receptor Agonists

Bioisosteric replacement of the guanidino group in arpromidine‐like histamine H₂ receptor (H₂R) agonists by an acylguanidine moiety is useful for obtaining potent H₂R agonists with improved oral bioavailability and blood–brain barrier penetration. We show that bioisosteric replacement of the imidazole ring in N^G‐acylated imidazolylpropylguanidines by a 2‐aminothiazol‐5‐yl group resulted in potent H₂R agonists with much greater selectivity for the human H₂R over H₃ and H₄ receptors.

     

Solid fuels in chemical-looping combustion using a NiO-based oxygen carrier

The feasibility of using three different solid fuels in chemical-looping combustion (CLC) has been investigated using NiO as oxygen carrier. A laboratory fluidized-bed reactor system for solid fuel was used, simulating a chemical-looping combustion system by exposing the sample to alternating reducing and oxidizing conditions. In each reducing phase 0.2 g of fuel was added to the reactor containing 20 g oxygen carrier. The experiments were performed at 970 °C. Compared to previously published results with other oxygen carriers the reactivity of the used Ni-particles was considerably lower for the high-sulphur fuel and higher for the low-sulphur fuel. Much more unconverted CO was released and the fuel conversion was much slower for high-sulphur fuel such as petroleum coke, suggesting that the nickel-based oxygen carrier was deactivated by the presence of sulphur. The NiO particles also showed good reactivity with methane and a syngas mixture of 50% H₂ and 50% CO. For all experiments the oxygen carrier showed good fluidizing properties without any signs of agglomeration.     

Effect of fuel particle size on reaction rate in chemical looping combustion

Chemical looping combustion (CLC) uses an oxygen carrier circulating between an air and a fuel reactor to replace direct burning of fuels in air. The very low energy penalty for CO₂ separation in CLC gives it the potential to become an important technology on the way to a CO₂ neutral energy supply. In this work, the influence of the particle size of coal on the rate of reaction of the coal was investigated in a bed of oxygen carrier. In order to do this, a method to quench the reaction of coal with oxygen carriers at a specified time and measure the particle size distribution of the remaining coal was developed. Three size fractions of coal were used in the experiments: 90–125, 180–212 and 250–355 μm. Particle size distributions of the fuel show a decrease in particle size with time. The influence of devolatilisation of the coal on the coal particle size was measured, showing that coal particles do not break in the fluidized bed reactor used for the experiments. Reaction rates based on measurements of gas phase concentrations of CO₂, CO and CH₄ showed that the reaction rate is independent of the particle size. These results are in line with literature findings, as studies have shown that carbon gasification is size-independent at conditions similar to those in the performed CLC experiments.     

Powder recycling in laser beam melting: strategies,consumption modeling and influence on resource efficiency

Laser beam melting (LBM) is a powder-bed and laser-based additive manufacturing technology that is increasingly used for the production of metal components. For a sustainability assessment of a production technology, the global warming potential (GWP) can be used, which is commonly referred to as CO₂-footprint. Looking at the resource demand of LBM, material losses and powder recycling play a significant role. In the LBM build-up process, powder material is selectively solidified, generating the part layer-by-layer. The non-solidified powder material can be recycled, which is beneficial to the resource efficiency of the process. Due to considerations regarding powder quality degradation, the number of reuse powder cycles in industrial practice varies significantly, ranging from only one to more than several dozen cycles. Similarly, material losses during the process have shown to differ between LBM machines. However, previous approaches for LBM resource efficiency assessment lack a detailed representation of these two factors. In this study, two interacting models are introduced for the evaluation of the GWP of LBM parts. Firstly, a powder reuse cycle calculation model is described. Secondly, a LBM resource and energy consumption model based on the CO2PE!-methodology is put forward with a refined focus on powder recycling and material losses. The models are implemented and validated based on three LBM production use cases including the acquisition of resource and energy consumption data for three commercial LBM machines. GWP-impact values are used from the ProBas database, provided by the German Federal Environmental Agency. Based on the results regarding the three LBM use cases, the role of powder recycling and material losses on the GWP-impact of LBM during the production phase is discussed. The results show that the number of attainable powder reuse cycles lies around 35 cycles (ranging from 1 to 117 cycles) for the analyzed LBM production scenarios when applying the suggested powder recycling strategy. If powder is not recycled and only used once, more than 90% of the powder batch might be discarded. The volume-specific CO₂-equivalent of 0.175 kgCO₂eq/cm³ can be used as a rule of thumb for a quick estimation of the GWP for LBM parts made from Al-alloy or steel. Electric energy consumption constitutes for the largest share of GWP-impact, followed by the solidified metal powder and the occurring powder losses.     

Enantioselective rhodium-catalyzed C-C bond activations

The catalytic activation of carbon-carbon single bonds represents a major challenge in organometallic chemistry. Strained ring substrates occupy in this respect a privileged role as their inherent ring strain facilitates the desired metal insertion. Employing symmetrically substituted tert-cyclobutanols, an enantioselective rhodium(I)-catalyzed beta-carbon elimination creates alkyl-rhodium species bearing all-carbon quaternary stereogenic centers. Downstream reactions enable access to a wide range of synthetically versatile products such as substituted cyclohexenones, lactones and indanols with excellent enantioselectivities of up to 99% ee.     

Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging

Nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be at the core of nano-scaled drug delivery systems, namely functionalization of nanocarriers, delivery to target organs and in vivo imaging. The latest developments on highly specific conjugation strategies that are used to attach biomolecules to the surface of nanoparticles (NP) are first reviewed. Besides drug carrying capabilities, the functionalization of nanocarriers also facilitate their transport to primary target organs. We highlight the leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells surrounding the brain that prevents high-molecular weight molecules from entering the brain. The BBB has several transport molecules such as growth factors, insulin and transferrin that can potentially increase the efficiency and kinetics of brain-targeting nanocarriers. Potential treatments for common neurological disorders, such as stroke, tumours and Alzheimer's, are therefore a much sought-after application of nanomedicine. Likewise any other drug delivery system, a number of parameters need to be registered once functionalized NPs are administered, for instance their efficiency in organ-selective targeting, bioaccumulation and excretion. Finally, direct in vivo imaging of nanomaterials is an exciting recent field that can provide real-time tracking of those nanocarriers. We review a range of systems suitable for in vivo imaging and monitoring of drug delivery, with an emphasis on most recently introduced molecular imaging modalities based on optical and hybrid contrast, such as fluorescent protein tomography and multispectral optoacoustic tomography. Overall, great potential is foreseen for nanocarriers in medical diagnostics, therapeutics and molecular targeting. A proposed roadmap for ongoing and future research directions is therefore discussed in detail with emphasis on the development of novel approaches for functionalization, targeting and imaging of nano-based drug delivery systems, a cutting-edge technology poised to change the ways medicine is administered.     

Modularity in small machine tools

Up to now, machine tools in micro production hardly feature modularity and hence offer only few opportunities to reconfigure or individualize a manufacturing process. This article gives a summary of concepts, how modularity in small micro machine tools can be designed and implemented. A size-adaptable machine frame is the basis for various possible process layouts. Adapters, a feed module with replaceable drive and kinematics, equipped with appropriate interfaces as well as a supply concept are introduced to allow further configuration. The combination of those concepts characterizes a small modular machine tool system. Technical solutions and fully functional prototypes will be shown and discussed in the following paper.     

An amino-based protic ionic liquid as a corrosion inhibitor of mild steel in aqueous chloride solutions

Protic ionic liquids (PILs) have shown to be promising substances as corrosion inhibitors (CIs). In line with this, the aim of this study is to study the performance and propose the corrosion inhibition mechanism of N-methyl-2-hydroxyethylamine (M-2HEAOL) and bis-2-hidroxyethylamine (B-HEAOL) oleate, for mild steel, in a neutral chloride solution. Electrochemical characterization was conducted under static and hydrodynamic conditions, and it was revealed that M-2HEAOL and B-HEAOL worked as mixed-type CIs with more interference on the anodic reaction. Inhibition efficiency depended on the concentration reaching 97% of inhibition efficiency in 5 mmol/L concentration. Scanning electron microscopy, optical interferometry, Raman spectroscopy, and Fourier-transform infrared spectroscopy are used to elicit the chemical composition of the surface film and corrosion morphology of steel in the presence of CIs, the adsorption processes of which involved physical and chemical adsorption between metal and different parts of ionic liquids. The results allowed the proposition of a corrosion inhibition mechanism.     

New and Easily Accessible Nitrogen Acyclic Gold(I) Carbenes: Structure and Application in the Gold‐Catalyzed Phenol Synthesis as well as the Hydration of Alkynes

A series of gold(I) isonitrile complexes were prepared and converted to the corresponding diaminocarbene gold(I) complexes by reactions with primary and symmetrical secondary amines. Twelve crystal structure analyses of the gold(I) complexes could be obtained, in addition NMR studies allowed an analysis of the different diastereomers present in solution. In the gold‐catalyzed phenol synthesis these complexes were very successful as pre‐catalysts, reaching an unprecedented 3050 turnovers with a problematic substrate. Good conversions in the hydration of phenylacetylene could also be achieved.     

Endothelial Lipase Modulates Paraoxonase 1 Content and Arylesterase Activity of HDL

Endothelial lipase (EL) is a strong modulator of the high-density lipoprotein (HDL) structure, composition, and function. Here, we examined the impact of EL on HDL paraoxonase 1 (PON1) content and arylesterase (AE) activity in vitro and in vivo. The incubation of HDL with EL-overexpressing HepG2 cells decreased HDL size, PON1 content, and AE activity. The EL modification of HDL did not diminish the capacity of HDL to associate with PON1 when EL-modified HDL was incubated with PON1-overexpressing cells. The overexpression of EL in mice significantly decreased HDL serum levels but unexpectedly increased HDL PON1 content and HDL AE activity. Enzymatically inactive EL had no effect on the PON1 content of HDL in mice. In healthy subjects, EL serum levels were not significantly correlated with HDL levels. However, HDL PON1 content was positively associated with EL serum levels. The EL-induced changes in the HDL-lipid composition were not linked to the HDL PON1 content. We conclude that primarily, the interaction of enzymatically active EL with HDL, rather than EL-induced alterations in HDL size and composition, causes PON1 displacement from HDL in vitro. In vivo, the EL-mediated reduction of HDL serum levels and the consequently increased PON1-to-HDL ratio in serum increase HDL PON1 content and AE activity in mice. In humans, additional mechanisms appear to underlie the association of EL serum levels and HDL PON1 content.