Development of Lab-Scale Continuous Stirred-Tank Reactor as Flow Process Tool for Oxidation Reactions Using Molecular Oxygen.

The use of sustainable oxidants is of great interest to the chemical industry, considering the importance of oxidation reactions for the manufacturing of chemicals and society's growing awareness of its environmental impact. Molecular oxygen (O2), with an almost optimal atom efficiency in oxidation reactions, presents one of the most attractive alternatives to common reagents that are not only toxic in most cases but produce stoichiometric amounts of waste that must be treated. However, fire and explosion safety concerns, especially when used in combination with organic solvents, restrict its easy use. Here, we use state-of-the-art 3D printing and experimental feedback to develop a miniature continuous stirred-tank reactor (mini-CSTR) that enables efficient use of O2 as an oxidant in organic chemistry. Outstanding heat dissipation properties, achieved through integrated jacket cooling and a high surface-to-volume ratio, allow for a safe operation of the exothermic oxidation of 2-ethylhexanal, surpassing previously reported product selectivity. Moving well beyond the proof-of-concept stage, we characterize and illustrate the reactor's potential in the gas-liquid-solid triphasic synthesis of an endoperoxide precursor of antileishmanial agents. The custom-designed magnetic overhead stirring unit provides improved stirring efficiency, facilitating the handling of suspensions and, in combination with the borosilicate gas dispersion plate, leading to an optimized gas-liquid interface. These results underscore the immense potential that lies within the use of mini-CSTR in sustainable chemistry.

Up-scaling a Sol-Gel Process for the Production of a Multi-Component Xerogel Powder.

A sol-gel process for the synthesis of a multi-component oxide material from the system SiO2-ZrO2-Al2O3underwent optimization and up-scaling. Initially, on a laboratory scale, components including precursors, catalysts, and additives were methodically evaluated to ensure a safe and efficient transition to larger volumes. Subsequently, the equipment for the whole setup of the sol-gel process was strategically selected. Leveraging insights from these optimizations, the process was successfully scaled-up to pilot-scale operation, conducting hydrolysis, condensation reactions, gelation, aging, and drying within a single, integrated conical dryer system for an 80 L batch. A visual test and FTIR spectroscopy were applied for process control and monitoring.

Aiming for More Sustainable Cross-Coupling Chemistry by Employing Single-Atom Catalysis on Scale.

Scaling up syntheses from mg to kg quantities is a complex endeavor. Besides adapting laboratory protocols to industrial processes and equipment and thorough safety assessments, much attention is paid to the reduction of the process' environmental impact. For processes including transition metal catalyzed steps, e.g. cross-coupling chemistry, this impact strongly depends on the identity of the metal used. As such, a key approach is the replacement of single-use with reusable heterogeneous catalysts. Transition metal single-atom heterogeneous catalysts (SAC), a novel class of catalytic materials, might exhibit all the necessary properties to step up to this task. This article shall discuss current applications of SAC in cross-coupling chemistry from the point of a process chemist and shed light on the NCCR Catalysis contribution to the field. Investigations of the stability-activity-selectivity relationship of SACs in combination with early-stage life-cycle assessments (LCA) of potential processes lay the foundation for large-scale application tailored catalyst synthesis. Ultimately, prevailing challenges are highlighted, which need to be addressed in future research.

Education in Flow Chemistry.

Flow chemistry is a growing and promising technology that can be used in research, development, and production. Nowadays, properly trained staff in flow chemistry is lacking in industry. To efficiently work with this technology, a mix of engineering and chemical skills is required. Although, this dual education is well addressed in the chemistry major given at the Haute Ecole d'Ingénierie et d'Architecture de Fribourg, a school of the University of Applied Sciences and Arts, Western Switzerland, the teaching in flow chemistry should be enhanced and reinforced.

Reaction Environment Design for Multigram Synthesis via Sonogashira Coupling over Heterogeneous Palladium Single-Atom Catalysts.

Single-atom heterogeneous catalysts (SACs) attract growing interest in their application in green chemistry and organic synthesis due to their potential for achieving atomic-level precision. These catalysts offer the possibility of achieving selectivity comparable to the traditionally applied organometallic complexes, while enhancing metal utilization and recovery. However, an understanding of SAC performance in organic reactions remains limited to model substrates, and their application as drop-in solutions may not yield optimal activity. Here, we investigate the previously unaddressed influence of the reaction environment, including solvent, base, cocatalyst, and ligand, on the performance of a palladium SAC in Sonogashira-Hagihara cross-couplings. By examining the effects of different solvents using the established criteria, we find that the behavior of the SAC deviates from trends observed with homogeneous catalysts, indicating a distinct interplay between heterogeneous systems and the reaction environment. Our results illustrate the satisfactory performance of SACs in cross-couplings of aryl iodides and acetylenes with electron-withdrawing and -donating groups, while the use of bromides and chlorides remains challenging. Extending the proof-of-concept stage to multigram scale, we demonstrate the synthesis of an intermediate of the anticancer drug Erlotinib. The catalyst exhibits high stability, allowing for multiple reuses, even under noninert conditions. Life-cycle assessment guides the upscaling of the catalyst preparation and quantifies the potential environmental and financial benefits of using the SAC, while also revealing the negligible impact of the PPh3 ligand and CuI cocatalyst. Our results underscore the significant potential of SACs to revolutionize sustainable organic chemistry and highlight the need for further understanding the distinct interplay between their performance and the reaction environment.

A Review of Polylactic Acid as a Replacement Material for Single-Use Laboratory Components.

Every year, the EU emits 13.4 Mt of CO2 solely from plastic production, with 99% of all plastics being produced from fossil fuel sources, while those that are produced from renewable sources use food products as feedstocks. In 2019, 29 Mt of plastic waste was collected in Europe. It is estimated that 32% was recycled, 43% was incinerated and 25% was sent to landfill. It has been estimated that life-sciences (biology, medicine, etc.) alone create plastic waste of approximately 5.5 Mt/yr, the majority being disposed of by incineration. The vast majority of this plastic waste is made from fossil fuel sources, though there is a growing interest in the possible use of bioplastics as a viable alternative for single-use lab consumables, such as petri dishes, pipette tips, etc. However, to-date only limited bioplastic replacement examples exist. In this review, common polymers used for labware are discussed, along with examining the possibility of replacing these materials with bioplastics, specifically polylactic acid (PLA). The material properties of PLA are described, along with possible functional improvements dure to additives. Finally, the standards and benchmarks needed for assessing bioplastics produced for labware components are reviewed.

Desde la periferia: la noción de espacio social en la movilización sociopolítica de la juventud / From the periphery: The notion of social space in the socio-political mobilization of youth / Da partir da periferia: A noção de espaço social na mobilização sócio-política da juventude

Resumen (analítico) Este artículo pone de manifiesto la existencia de un elemento transversal en la relación de la juventud con la esfera pública, que contribuye a comprender mejor la naturaleza de sus expresiones políticas: la asimilación de una cierta posición periférica impuesta dentro del espacio social. La idea de espacio social, y en particular la de periferia, contribuyen a dar coherencia a determinados fenómenos y tendencias de la movilización sociopolítica de la juventud en su conjunto. Para ello, se analizan tres movimientos juveniles surgidos en Barcelona durante el año 2019, en los que la juventud tuvo especial protagonismo. Las diferencias y similitudes entre los tres movimientos muestran la versatilidad de la noción de periferia, que sirve para visualizar la precariedad vital que identifica a toda una generación, más allá de sus diferencias.

Abstract (analytical) This article highlights the existence of a transversal element in the relationship of youth with the public sphere, which contributes to a better understanding of the nature of their political expressions: the internalization of a certain imposed peripheral position within the social space. The idea of social space, and in particular the idea of periphery, contributes to give coherence to some phenomena and trends on the sociopolitical mobilization of youth as a whole. To do this, three youth movements emerged in Barcelona during 2019 are analyzed, in which the youth played a special role. The differences and similarities between the three movements show the versatility of the notion of periphery, which serves to visualize the vital precariousness that identifies an entire generation, beyond their internal differences.

Resumo (analítico) Este artigo tem como objetivo destacar a existência de um elemento transversal na relação dos jovens com a esfera pública, o que contribui para a melhor compreensão da natureza de suas expressões políticas: a assimilação de uma determinada posição periférica imposta dentro do espaço social. A ideia de espaço social e, em particular, de periferia, contribui para dar coerência a certos fenômenos e tendências na mobilização sócio-política da juventude como um todo. Para isso, são analisados três movimentos juvenis surgidos em Barcelona em 2019, nos quais os jovens tiveram protagonismo especial. As diferenças e semelhanças entre os três movimentos mostram a versatilidade da noção de periferia, que serve para visualizar a precariedade vital que identifica uma geração inteira, além de suas diferenças internas.

Melt Polycondensation for the Synthesis of Polyester Amides using Kneader Reactor Technology.

In this work, we discuss the process development and scale-up of the melt polycondensation of polyester amides from a laboratory scale to kg-scale in a kneader reactor. We identified and optimized the most important critical parameters and produced kg-quantities of polyester amides with Mn up to 25'000 g/mol and reproducible thermal and mechanical properties. The special kneader reactor allows safe and efficient scale-up of polymerisation reactions at high temperature and viscous melts due to good mixing and efficient mass transfer.

The Vitamin C Analogue 2-O-ß-D-Glucopyranosyl-L-ascorbic Acid in Rhizomes, Stems and Leaves of Lycium barbarum.

Awareness of health benefits of goji berries coming from their bioactive compounds, mostly antioxidants like ascorbic acid, has grown. Recently, an ascorbic acid analogue from goji berries, the 2-O-ß-D-glucopyranosyl-L-ascorbic acid has been reported. In rats, the analogue is absorbed intact and in the form of free vitamin C and consequently has been proposed as a provitamin C. Synthesis of the analogue is demanding and laborious and therefore reliable natural sources are searched. Knowledge concerning the analogue's occurrence in other parts of goji plant is lacking. The aim of this study was to evaluate the contents of 2-O-ß-D-glucopyranosyl-L-ascorbic acid in rhizomes, stems and leaves from Lycium barbarum. Rhizomes, stems and leaveswere extracted and the content of 2-O-ß-D-glucopyranosyl-L-ascorbic acid and non glucosylated, free ascorbic acid was determined by HPLC-DAD. 2-O-ß-D-glucopyranosyl-L-ascorbic acid was found in all goji plant tissues investigated. Based on dry weight, 3.34 mg/100 g were found in the leaves, 4.05 mg/100 g in the stems and up to 12.6 mg/100 g in the rhizomes. Nevertheless, the analogue content in goji berries is much higher (40 to 280 mg/100 g dry weight). The present study confirmed the presence of 2-O-ß-D-glucopyranosyl-L-ascorbic acid in rhizomes, stems and leaves of Lycium barbarum. However, their content compared to goji berries is considerably lower.

4-epi-Isofagomine derivatives as pharmacological chaperones for the treatment of lysosomal diseases linked to ß-galactosidase mutations: Improved synthesis and biological investigations.

(5aR)-5a-C-pentyl-4-epi-isofagomine 1 is a powerful inhibitor of lysosomal ß-galactosidase and a remarkable chaperone for mutations associated with GM1-gangliosidosis and Morquio disease type B. We report herein an improved synthesis of this compound and analogs (5a-C-methyl, pentyl, nonyl and phenylethyl derivatives), and a crystal structure of a synthetic intermediate that confirms its configuration resulting from the addition of a Grignard reagent. These compounds were evaluated as glycosidase inhibitors and their potential as chaperones for mutant lysosomal galactosidases determined. Based on these results and on docking studies, the 5-C-pentyl derivative 1 was selected as the optimal structure for further investigations: this compound induces the maturation of mutated ß-galactosidase in fibroblasts of a GM1-gangliosidosis patient and promote the decrease of keratan sulfate and oligosaccharide load in patient cells. Compound 1 is clearly capable of restoring ß-galactosidase activity and of promoting maturation of the protein, which should result in significant clinical benefit. These properties strongly support the development of compound 1 for the treatment of GM1-gangliosidosis and Morquio disease type B patients harboring ß-galactosidase mutations sensitive to pharmacological chaperoning.

One-Pot Synthesis of Trifluoromethylated Quinazolin-4(3 H)-ones with Trifluoroacetic Acid as CF3 Source.

A novel and convenient one-pot sequential cascade method for the preparation of 2-trifluoromethylquinazolin-4(3 H)-ones is described. Trifluoroacetic acid (TFA) was employed as inexpensive and readily available CF3 source, which in the presence of T3P was condensed with a variety of anthranilic acids and amines to provide the products in up to 75% yield. The protocol was proved to be robust on 80 g scale, and the synthetic versatility of the prepared quinazolinon-4-ones was demonstrated by derivatization to further useful building blocks.

Continuous Processes and Flow Chemistry at the Universities of Applied Sciences in Switzerland.

This article provides an overview of activities in the fields of continuous processes, flow chemistry and microreactors at the Universities of Applied Sciences in Switzerland.

Complete Genome Sequence of Escherichia coli ABWA45, an rmtB-Encoding Wastewater Isolate.

We present the complete genome sequence of Escherichia coli ABWA45, a 16S rRNA methyltransferase-producing wastewater isolate. Assembly and annotation resulted in a 5,094,639-bp circular chromosome and four closed plasmids of 145,220 bp, 113,793 bp, 57,232 bp, and 47,900 bp in size. Furthermore, a small open plasmid (7,537 bp in size) was assembled.

Draft Genome Sequence of Klebsiella pneumoniae 704SK6, an OXA-48- and CTX-M-15-Encoding Wastewater Isolate.

The Swiss wastewater isolate Klebsiella pneumoniae 704SK6, encoding OXA-48 and CTX-M-15 ß-lactamases, was fully sequenced. The assembly resulted in an open chromosome of 5,208,104 bp in size (G+C content, 57.6%) and four closed plasmid sequences of 209,651, 197,670, 65,998, and 63,605 bp in size.

Complete Genome Sequence of Enterobacter cloacae 704SK10, an OXA-48-Encoding Wastewater Isolate.

Here we present the complete genome sequence of Enterobacter cloacae 704SK10, a Swiss wastewater isolate encoding an OXA-48 carbapenemase. Assembly resulted in closed sequences of the 4,876,946-bp chromosome, a 111,184-bp IncF plasmid, and an OXA-48-encoding IncL plasmid (63,458 bp) nearly identical to the previously described plasmid pOXA-48.

Complete Genome Sequence of Citrobacter freundii 705SK3, an OXA-48-Encoding Wastewater Isolate.

We present the genome sequence of Citrobacter freundii 705SK3, a wastewater isolate harboring an IncL OXA-48-encoding plasmid. Assembly of the genome resulted in a 5,242,839-bp circular chromosome (GC content, 52%) and two closed plasmids of 296,175 bp and 63, 458 bp in size.

Biofilm Formation Potential of Heat-Resistant Escherichia coli Dairy Isolates and the Complete Genome of Multidrug-Resistant, Heat-Resistant Strain FAM21845.

We tested the biofilm formation potential of 30 heat-resistant and 6 heat-sensitive Escherichia coli dairy isolates. Production of curli and cellulose, static biofilm formation on polystyrene (PS) and stainless steel surfaces, biofilm formation under dynamic conditions (Bioflux), and initial adhesion rates (IAR) were evaluated. Biofilm formation varied greatly between strains, media, and assays. Our results highlight the importance of the experimental setup in determining biofilm formation under conditions of interest, as correlation between different assays was often not a given. The heat-resistant, multidrug-resistant (MDR) strain FAM21845 showed the strongest biofilm formation on PS and the highest IAR and was the only strain that formed significant biofilms on stainless steel under conditions relevant to the dairy industry, and it was therefore fully sequenced. Its chromosome is 4.9 Mb long, and it harbors a total of five plasmids (147.2, 54.2, 5.8, 2.5, and 1.9 kb). The strain carries a broad range of genes relevant to antimicrobial resistance and biofilm formation, including some on its two large conjugative plasmids, as demonstrated in plate mating assays.IMPORTANCE In biofilms, cells are embedded in an extracellular matrix that protects them from stresses, such as UV radiation, osmotic shock, desiccation, antibiotics, and predation. Biofilm formation is a major bacterial persistence factor of great concern in the clinic and the food industry. Many tested strains formed strong biofilms, and especially strains such as the heat-resistant, MDR strain FAM21845 may pose a serious issue for food production. Strong biofilm formation combined with diverse resistances (some encoded on conjugative plasmids) may allow for increased persistence, coselection, and possible transfer of these resistance factors. Horizontal gene transfer may conceivably occur in the food production setting or the gastrointestinal tract after consumption.

Turn Up the Heat-Food and Clinical Escherichia coli Isolates Feature Two Transferrable Loci of Heat Resistance.

Heat treatment is a widely used process to reduce bacterial loads in the food industry or to decontaminate surfaces, e.g., in hospital settings. However, there are situations where lower temperatures must be employed, for instance in case of food production such as raw milk cheese or for decontamination of medical devices such as thermo-labile flexible endoscopes. A recently identified locus of heat resistance (LHR) has been shown to be present in and confer heat resistance to a variety of Enterobacteriaceae, including Escherichia coli isolates from food production settings and clinical ESBL-producing E. coli isolates. Here, we describe the presence of two distinct LHR variants within a particularly heat resistant E. coli raw milk cheese isolate. We demonstrate for the first time in this species the presence of one of these LHRs on a plasmid, designated pFAM21805, also encoding type 3 fimbriae and three bacteriocins and corresponding self-immunity proteins. The plasmid was highly transferable to other E. coli strains, including Shiga-toxin-producing strains, and conferred LHR-dependent heat resistance as well as type 3 fimbriae-dependent biofilm formation capabilities. Selection for and acquisition of this "survival" plasmid by pathogenic organisms, e.g., in food production environments, may pose great concern and emphasizes the need to screen for the presence of LHR genes in isolates.