Taylor Bubble Study of the Influence of Fluid Dynamics on Yield and Selectivity in Fast Gas-Liquid Reactions

A consecutive competitive gas-liquid reaction is investigated using a Taylor bubble setup regarding the influence of fluid mixing in the bubble wake on yield and selectivity. The concentration fields behind a Taylor bubble are visualized and measured quantitatively with a novel time-resolved absorption imaging technique based on Beer Lamberts law and an integral selectivity is derived. In addition, the calculation of the local selectivity, often used in numerical approaches, is discussed and the existing experimental limits for its derivation are pointed out. Finally, an increase in selectivity of a competitive consecutive reaction for enhanced mixing is experimentally confirmed.     

From Oxadiazole to Triazole Analogues: Optimization toward a Dual Orexin Receptor Antagonist with Improved in vivo Efficacy in Dogs

The orexin system is responsible for regulating the sleep-wake cycle. Suvorexant, a dual orexin receptor antagonist (DORA) is approved by the FDA for the treatment of insomnia disorders. Herein, we report the optimization efforts toward a DORA, where our starting point was (5-methoxy-4-methyl-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-[5-(2-trifluoromethoxy-phenyl)-[1,2,4]oxadiazol-3-yl]-pyrrolidin-1-yl}methanone ( 6 ), a compound which emerged from our in-house research program. Compound 6 was shown to be a potent, brain-penetrating DORA with in vivo efficacy similar to suvorexant in rats. However, shortcomings from low metabolic stability, high plasma protein binding (PPB), low brain free fraction (f_u brain), and low aqueous solubility, were identified and hence, compound 6 was not an ideal candidate for further development. Our optimization efforts addressing the above-mentioned shortcomings resulted in the identification of (4-chloro-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-methyl-2-[5-(2-trifluoromethoxy-phenyl)-4H-[1,2,4]triazol-3-yl]-pyrrolidin-1-yl}l-methanone ( 42 ), a DORA with improved in vivo efficacy compared to 6 .     

Enhancing the sweetening power of lactose by enzymatic modification in the reformulation of dairy products

Lactose solutions of up to 50% (w/v) were incubated with lactases and glucose isomerases for subsequent implementation in dairy product samples to enhance sweetness. A degree of hydrolysis of >90% and of isomerisation of 50% were attainable. The sensory sweetening power of lactose in solutions of up to 50% (w/v) can be enhanced 2–3 times. Based on sensory experiments, application of this bi‐enzymatic system in yoghurt and pudding samples allowed for a 10–20% (w/w) reduction in the total sugar content, whilst retaining equal sweetness. The growth of yoghurt starter cultures was not affected, yet furosine formation more than doubled in high heated, enzyme‐modified milk.     

Nano-Design für Makroschichten

Nano design for macroscopic coatings – new application potentials by PVD coatings up to 100 μm thickness Non-homogeneous coatings still limit the application of thicker layers due to defect growth and irregular layer thickness distribution along the surface of complex shaped components. Therefore, the layer thickness is usually limited to about 10 μm. In order to limit the surface roughness by the growing layer, multilayer coating systems are deposited by highly ionized plasmas. This allows significantly smoother layers to be produced, which until now could only be produced by mechanical finishing. Furthermore, by combining selected material systems and targeted parameter selection, structures can be deposited during coating, especially on edges, which result in a reduction of the cutting edge radius. In future, edge geometries should therefore be able to be specifically adjusted through the coating process.     

The Alkylquinolone Repertoire of Pseudomonas aeruginosa is Linked to Structural Flexibility of the FabH‐like 2‐Heptyl‐3‐hydroxy‐4(1H)‐quinolone (PQS) Biosynthesis Enzyme PqsBC

Pseudomonas aeruginosa is a bacterial pathogen that causes life‐threatening infections in immunocompromised patients. It produces a large armory of saturated and mono‐unsaturated 2‐alkyl‐4(1H)‐quinolones (AQs) and AQ N‐oxides (AQNOs) that serve as signaling molecules to control the production of virulence factors and that are involved in membrane vesicle formation and iron chelation; furthermore, they also have, for example, antibiotic properties. It has been shown that the β‐ketoacyl‐acyl‐carrier protein synthase III (FabH)‐like heterodimeric enzyme PqsBC catalyzes the last step in the biosynthesis of the most abundant AQ congener, 2‐heptyl‐4(1H)‐quinolone (HHQ), by condensing octanoyl‐coenzyme A (CoA) with 2‐aminobenzoylacetate (2‐ABA), but the basis for the large number of other AQs/AQNOs produced by P. aeruginosa is not known. Here, we demonstrate that PqsBC uses different medium‐chain acyl‐CoAs to produce various saturated AQs/AQNOs and that it also biosynthesizes mono‐unsaturated congeners. Further, we determined the structures of PqsBC in four different crystal forms at 1.5 to 2.7 Å resolution. Together with a previous report, the data reveal that PqsBC adopts open, intermediate, and closed conformations that alter the shape of the acyl‐binding cavity and explain the promiscuity of PqsBC. The different conformations also allow us to propose a model for structural transitions that accompany the catalytic cycle of PqsBC that might have broader implications for other FabH‐enzymes, for which such structural transitions have been postulated but have never been observed.     

Microstructured Fischer‐Tropsch Reactor Scale‐up and Opportunities for Decentralized Application

Current projects focusing on the energy transition in traffic will rely on a high‐level technology mix for their commissioning. One of those technologies is the Fischer‐Tropsch synthesis (FTS) that converts synthesis gas into hydrocarbons of different chain lengths. A microstructured packed‐bed reactor for low‐temperature FTS is tested towards its versatility for biomass‐based syngas with a high inert gas dilution. Investigations include overall productivity, conversion, and product selectivity. A 60‐times larger pilot‐scale reactor is further tested. Evaporation cooling is introduced which allows to increase the available energy extraction from the system. From that scale on, an autothermal operation at elevated conversion levels is applicable.     

A flexible air separation process: 1. Design and steady-state optimizations

The flexible operation of energy-intensive processes, such as cryogenic air separation, has economic potential due to increasing fluctuations of the electricity markets. Multiproduct air separation processes with high ratios of liquid product are very promising for flexible operation due to storable products. We present a process design with an integrated liquefication cycle and liquid assist operation, that facilitates a high liquid product ratio and a flexible process operation. We use a mechanistic dynamic process model in steady-state process optimizations covering the wide operational range of the proposed process. The optimization results show that the power demand can be varied in a range from 3.5 to 28 MW without violating operational constraints by changing the nitrogen and oxygen production rates. Thus, the proposed process is a promising air separation candidate for flexible operation with respect to fluctuating electricity markets.     

Structure–Function Relationship of Retinal Ganglion Cells in Multiple Sclerosis

The retinal ganglion cells (RGC) may be considered an easily accessible pathophysiological site of degenerative processes in neurological diseases, such as the RGC damage detectable in multiple sclerosis (MS) patients with (HON) and without a history of optic neuritis (NON). We aimed to assess and interrelate RGC functional and structural damage in different retinal layers and retinal sites. We included 12 NON patients, 11 HON patients and 14 healthy controls for cross-sectional multifocal pattern electroretinography (mfPERG) and optical coherence tomography (OCT) measurements. Amplitude and peak times of the mfPERG were assessed. Macula and disc OCT scans were acquired to determine macular retinal layer and peripapillary retinal nerve fiber layer (pRNFL) thickness. In both HON and NON patients the foveal N2 amplitude of the mfPERG was reduced compared to controls. The parafoveal P1 peak time was significantly reduced in HON only. For OCT, parafoveal (pfGCL) and perifoveal (pGCL) ganglion cell layer thicknesses were decreased in HON vs. controls, while pRNFL in the papillomacular bundle sector (PMB) showed reductions in both NON and HON. As the mfPERG derived N2 originates from RGC axons, these findings suggest foveal axonal dysfunction not only in HON, but also in NON patients.