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Miniaturization of MALDI Mass Spectrometers with the Technological Breakthrough of the Digital Ion Trap: Peptide and Protein Analysis in MS1, MS2, and MS3
Full text linkA digital ion trap (DIT) mass spectrometer was developed to extend the mass range in comparison to conventional ion traps. This was achieved by changing the RF voltage from a sinusoidal to a rectangular waveform. In addition to the extended mass range, the size of the instrument was miniaturized. To show the benefits of this development, MALDI applications in MS1, MS2, and MS3 are presented: On one hand, it is possible to analyze intact proteins, on the other hand the instrument enables insights into the structure of antibodies and glycoproteins after enzymatic digestion and collision-induced dissociation (CID)
Perfusion-Based Antibody Production in the Ambr® 250 Modular
Full text linkThe perfusion mode has become increasingly important in biopharmaceutical production in recent years. A bioreactor system used in many laboratories for the development of monoclonal antibodies (mAbs) production processes is the Sartorius’ Ambr. 250 system. Vessels designed for perfusion mode are only available for its high throughput version, while the modular version of the Ambr 250 is not designed for perfusion mode. In this study, perfusion processes for the production of a mAb with Chinese Hamster Ovary (CHO) cells were realized in the Ambr 250 Modular in combination with Repligen’s ATF 1 single-use device for the first time, to the authors’ knowledge. After testing a semi-perfusion setup in well plates and the Ambr 250, an N−1 perfusion process was developed to produce ultra-high cell densities of more than 150 Å~ 106 cells mL−1 for the inoculation of subsequent mAb production processes. In a second step, continuous mAb production was successfully realized over 23 days in a proof-of-concept experiment, achieving a volumetric productivity of 0.65 g L−1 d−1. The results of the N−1 and continuous perfusion processes were comparable to a 3 L HyPerformaTM Glass bioreactor (Thermo Scientific) with an ATF 2 (Repligen)
Learning Chemical Intuition: From Molecular Models to Neural Networks: Chemical Education
No full textThis article examines how both chemists and neural networks learn to predict chemical reactivity through different yet complementary frameworks, exploring how to effectively combine human chemical intuition with machine learning
Investigation of Pt-based Model Catalysts for Propane Dehydrogenation Reaction
Full text linkLarge scale exploitation of shale gas has stimulated the developments of on-purpose propane dehydrogenation (PDH) technologies. Pt-based PDH catalysts have been utilized in industry, e.g. Pt-Sn/Al2O3 and Pt-Ga/ Al2O3, where the actual role of metal dopants is not fully understood. In this regard, the development of model systems possessing tailored surface sites is necessary in order to look into the structure-activity relationships. In that context, the surface organometallic chemistry (SOMC) approach has emerged as a powerful tool to yield PDH model catalysts, revealing that the formation of alloyed particles and residual unreduced metal sites are important for high productivity and stability
Hybrid Enabling Technologies for Organic Synthesis
Full text linkIn this personal perspective, hybrid-enabling technologies refer to the integration of multiple methodologies, platforms, and technologies in organic synthesis to achieve more efficient, selective and sustainable chemical reactions. These technologies often combine with traditional or classical synthetic methods towards innovative synthetic approaches to address the challenges of conventional organic synthesis. This perspective emphasizes the utilization of enabling methods, with flow chemistry at the forefront, to achieve more sustainable production of biomolecules, agrochemicals as well as pharmaceuticals
Trace-level Multi-residue Analysis of Pesticides in Soil: Advances, Challenges, and Future Directions
Full text linkPesticides are frequently applied in large quantities in agriculture, resulting in their widespread presence in agricultural areas. Additionally, processes such as drift and volatilization contribute to their dispersion far beyond treated sites. However, systematic soil monitoring remains limited. To assess pesticide exposure to soil organisms, highly sensitive, accurate, and robust multi-residue analytical methods are essential. Given the wide variety of pesticides applied, monitoring those most likely to adversely affect soil health and terrestrial ecosystems is a prerequisite. Soil is one of the most complex environmental matrices, posing significant challenges throughout the entire analytical workflow. Here, we summarize the historical evolution of pesticide analysis in soil, outline key methodological advances, and discuss major challenges that must be addressed along the whole analytical workflow to enable effective soil monitoring. Ultimately, protecting soil requires both analytical and regulatory progress, as part of a broader set of measures
Innovation in Route Design, (Bio)Catalysis and Process Development Applied to the Second Generation Synthesis of Sacubitril
Full text linkCommercial manufacturing processes in the pharmaceutical industry need to address numerous goals, ranging from cost effectiveness over process safety to environmental sustainability. While the design of the synthetic route may commonly be considered the centerpiece of chemical process development, only the combination with innovative technologies at scale and in-depth process understanding can unlock the full potential of a synthetic route. The development of a second-generation synthesis of sacubitril, one of the constituent active pharmaceutical ingredients of LCZ696, serves as an example to display how synthesis design can be successfully combined with (bio)catalysis and thorough process development to achieve superior results. In addition, the case at hand highlights the multidisciplinary and team-focused nature of chemical process development
Greener synthesis of a potent proteolysis targeting chimera (PROTAC) degrader of indoleamine-2, 3-dioxygenase 1 (hDOI1): FH-HES (Universities of Applied Sciences)
No full textThe synthesis of the potential indoleamine-2, 3-dioxygenase 1 (IDO1) degrader proteolysis-targeting chimeras (PROTAC) using sustainable reagents and technologies such as ionic liquids and photochemical couplings was investigated. The ligand to the protein of interest, an indole derivative, was synthesized successfully for three substrates bearing different substituents (NO2, (CF3)2 and H) over three steps with good to satisfactory results with overall yields ranging from 21 to 71%. However, the coupling with the ubiquitin ligase, pomalidomide, was unsuccessful due to the degradation of the reactive diazoketone functional group
