Toward an e-chemistree: Materials for electrification of the chemical industry

Due to our increasing awareness of the impact of climate change on our society, unit operations in our manufacturing processes, including those in chemical industry, have to be greenified and made less dependent of fossil resources. This so-called electrification of the chemical industry is still yet in its infancy but there are many scientific and technological challenges to be solved. This article provides some directions for further research for scientists in both academia and industry to move step by step to an e-chemistree. These important but far from trivial energy and materials transitions require not only the introduction of new ways of heat management and other, often not yet fully explored, chemical conversion processes in which green electrons are used, but also the development of new materials including large-scale heating coils, easily chargeable battery systems as well as catalyst materials. For each of these developments, there is the issue of materials scarcity as well as durability as the introduction of these production processes should also be cost effective and overall more sustainable than the existing ones. Graphical abstract

Measurement of high protein concentrations by optical rotation: a case study for monitoring of monoclonal antibody drug downstream processes

Background: Recent advancements in cell engineering and bioreactor engineering have enabled high monoclonal antibody (mAb) concentrations in harvested solutions for the downstream process (DSP). Methods: As many unit operations such as capture chromatography, polish chromatography, membrane filtration, virus inactivation, virus filtration, and concentration by ultrafiltration are involved in DSP, it is crucial to monitor the process carefully in order to perform reliable and stable DSP operations. One of the most important signals (process parameter) to be monitored is the protein concentration CP. Although various methods are available, most of them are not suited for measuring high CP. In this paper, we have developed a method for measuring very high CP by optical rotation (OR). Result: Linear correlations were confirmed between OR and CP in the range CP = 0 to 80 g/L for mAbs with high repeatability and small variation coefficients. This method was applied to the monitoring of CP in the opaque (colored) solution during the cell culture. The CP by OR was in good agreement with those by the standard Protein A HPLC method. Conclusion: Monitoring of high CP by OR is expected to be an efficient process analytical tool (PAT) for DSP.

Synthesis of deoxymannojirimycin using a Ruthenium-catalysed hydrogen borrowing reaction

<p>1-Deoxymannojirimycin (DMJ) has been investigated as a potential anti-cancer therapy due to its specific inhibition of class I α-mannosidase enzymes, which has been shown to trigger ER stress and the Unfolded Protein Response (UPR) pathway, leading to apoptosis in human hepatocarcinoma cells. Current methods for the synthesis of DMJ consist of multiple steps and often result in poor yields. The objectives of this research project were to develop a scale-up suitable synthesis of deoxymannojirimycin (DMJ), and to assess the feasibility of telescoping key-reactions to reduce the number of unit operations. Synthetic efforts focused on the key conversion of 1 to 2 have previously involved separate oxidation and reduction steps. In our laboratory; attempts to use hydrogen-borrowing chemistry had taken >48hr and not been achieved in high yield. The highlights of this work were that this conversion was ultimately realised in 95% yield in 24hr, and that the final deprotection of (2) could be telescoped into the process removing reaction-workup and chromatographic steps. The ruthenium catalyst used in the hydrogen borrowing reaction was found to be extremely air-sensitive, with reactions taking place in carefully prepared reaction vessels under an atmosphere of dry argon gas. The catalyst was also found to exhibit sensitivities to materials such as metal needles and polymer tubing, preventing sampling and monitoring of the reaction during synthesis. This study demonstrated that a one-pot synthesis is feasible,compressing the final steps in the synthesis of DMJ in excellent yield. The difficulty arises from the sensitive nature of the ruthenium catalyst, and the extreme care required in the preparation of the glassware and reagents used in synthesis. Many aspects of this development require further investigation, including the sampling, monitoring and quality control of each synthetic step.</p>

Synthesis of deoxymannojirimycin using a Ruthenium-catalysed hydrogen borrowing reaction

<p>1-Deoxymannojirimycin (DMJ) has been investigated as a potential anti-cancer therapy due to its specific inhibition of class I α-mannosidase enzymes, which has been shown to trigger ER stress and the Unfolded Protein Response (UPR) pathway, leading to apoptosis in human hepatocarcinoma cells. Current methods for the synthesis of DMJ consist of multiple steps and often result in poor yields. The objectives of this research project were to develop a scale-up suitable synthesis of deoxymannojirimycin (DMJ), and to assess the feasibility of telescoping key-reactions to reduce the number of unit operations. Synthetic efforts focused on the key conversion of 1 to 2 have previously involved separate oxidation and reduction steps. In our laboratory; attempts to use hydrogen-borrowing chemistry had taken >48hr and not been achieved in high yield. The highlights of this work were that this conversion was ultimately realised in 95% yield in 24hr, and that the final deprotection of (2) could be telescoped into the process removing reaction-workup and chromatographic steps. The ruthenium catalyst used in the hydrogen borrowing reaction was found to be extremely air-sensitive, with reactions taking place in carefully prepared reaction vessels under an atmosphere of dry argon gas. The catalyst was also found to exhibit sensitivities to materials such as metal needles and polymer tubing, preventing sampling and monitoring of the reaction during synthesis. This study demonstrated that a one-pot synthesis is feasible,compressing the final steps in the synthesis of DMJ in excellent yield. The difficulty arises from the sensitive nature of the ruthenium catalyst, and the extreme care required in the preparation of the glassware and reagents used in synthesis. Many aspects of this development require further investigation, including the sampling, monitoring and quality control of each synthetic step.</p>

Isolation and Purification of a Hydrophobic Non-Ribosomal Peptide from an Escherichia coli Fermentation Broth

Non-ribosomal peptide synthases (NRPSs) generate versatile bioactive peptides by incorporating non-proteinogenic amino acids and catalyzing diverse modifications. Here, we developed an efficient downstream process for the capture, intermediate purification and polishing of a rhabdopeptide (RXP) produced by the NRPS VietABC. Many typical unit operations were unsuitable due to the similar physical and chemical properties of the RXP and related byproducts. However, we were able to capture the RXP from a fermentation broth using a hydrophobic resin (XAD-16N), resulting in a 14-fold increase in concentration while removing salts as well as polar and weak non-polar impurities. We then used ultra-high-performance liquid chromatography (UHPLC) for intermediate purification, with optimized parameters determined using statistical experimental designs, resulting in the complete removal of hydrophobic impurities. Finally, the UHPLC eluents were removed by evaporation. Our three-step downstream process achieved an overall product recovery of 81.7 ± 8.4%.