In 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.
{"title":"Hybrid Enabling Technologies for Organic Synthesis.","authors":"Upendra K Sharma","doi":"10.2533/chimia.2025.424","DOIUrl":"https://doi.org/10.2533/chimia.2025.424","url":null,"abstract":"<p><p>In 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.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 6","pages":"424-432"},"PeriodicalIF":1.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Continuous flow technology has matured into a valuable and widely exploited technology across academic and industrial laboratories. The safe and on-demand generation of reactive intermediates using miniaturized flow set-ups is of particular value to realize safer and more streamlined synthesis routes yielding important chemical building blocks. This focused review provides an update on recent studies highlighting the use of photochemistry, metalation reactions and electrochemistry to generate a variety of reactive intermediates showcasing successful implementations of flow processing as well as areas offering further opportunities.
{"title":"Generation and Use of Reactive Intermediates Exploiting Flow Technology.","authors":"Philip Jamieson, Davin Cronly, Marcus Baumann","doi":"10.2533/chimia.2025.396","DOIUrl":"https://doi.org/10.2533/chimia.2025.396","url":null,"abstract":"<p><p>Continuous flow technology has matured into a valuable and widely exploited technology across academic and industrial laboratories. The safe and on-demand generation of reactive intermediates using miniaturized flow set-ups is of particular value to realize safer and more streamlined synthesis routes yielding important chemical building blocks. This focused review provides an update on recent studies highlighting the use of photochemistry, metalation reactions and electrochemistry to generate a variety of reactive intermediates showcasing successful implementations of flow processing as well as areas offering further opportunities.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 6","pages":"396-403"},"PeriodicalIF":1.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Flow reaction data could have an outsized impact in the datasets which train the reaction prediction, chemical synthesis planning, and experiment design tools of tomorrow. This paper discusses why we should be increasing the availability of flow reaction data, and presents the Open Reaction Database as a schema and repository for such data. Best practices for defining flow reactions in the schema are discussed, highlighting those parts of the schema which are particularly relevant to flow reactions. Telescoped flow processes, and transient flow conditions are more complex to define in the schema, but options are presented for several typical scenarios. The paper concludes by opening a conversation with the flow chemistry community about how they would prefer to search for flow reaction data, and how to archive their own reaction data.
{"title":"WANTED: Flow Chemistry Reaction Data.","authors":"Benjamin J Deadman","doi":"10.2533/chimia.2025.390","DOIUrl":"https://doi.org/10.2533/chimia.2025.390","url":null,"abstract":"<p><p>Flow reaction data could have an outsized impact in the datasets which train the reaction prediction, chemical synthesis planning, and experiment design tools of tomorrow. This paper discusses why we should be increasing the availability of flow reaction data, and presents the Open Reaction Database as a schema and repository for such data. Best practices for defining flow reactions in the schema are discussed, highlighting those parts of the schema which are particularly relevant to flow reactions. Telescoped flow processes, and transient flow conditions are more complex to define in the schema, but options are presented for several typical scenarios. The paper concludes by opening a conversation with the flow chemistry community about how they would prefer to search for flow reaction data, and how to archive their own reaction data.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 6","pages":"390-395"},"PeriodicalIF":1.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kim-Long Diep, Emilie Buchs, Marlies Moser, Finn L Steinemann, Alain G Georg, Flavien L Morel, Michal Dabros, Roger Marti
Continuous processes (often referred to as flow chemistry) offers multiple advantages over batch processes and are of particular interest for industrial applications as they provide a more direct path towards process intensification, increased safety and efficiency. However, some chemical processes are still challenging to run in a continuous fashion, such as reactions producing fouling, using stoichiometric amounts of solids, or requiring long residence times. For those kinds of reactions, batch approaches are usually preferred even though some processes would still benefit from the advantages inherent to flow. We herein report our testing and development of a scalable continuous flow reactor equipped with active mixing that was designed to handle those challenging continuous processes, such as the continuous formation of a Grignard reagent from a magnesium powder slurry.
{"title":"A Scalable Dynamic Cascade Flow Reactor for Challenging Continuous Heterogeneous Processes.","authors":"Kim-Long Diep, Emilie Buchs, Marlies Moser, Finn L Steinemann, Alain G Georg, Flavien L Morel, Michal Dabros, Roger Marti","doi":"10.2533/chimia.2025.433","DOIUrl":"https://doi.org/10.2533/chimia.2025.433","url":null,"abstract":"<p><p>Continuous processes (often referred to as flow chemistry) offers multiple advantages over batch processes and are of particular interest for industrial applications as they provide a more direct path towards process intensification, increased safety and efficiency. However, some chemical processes are still challenging to run in a continuous fashion, such as reactions producing fouling, using stoichiometric amounts of solids, or requiring long residence times. For those kinds of reactions, batch approaches are usually preferred even though some processes would still benefit from the advantages inherent to flow. We herein report our testing and development of a scalable continuous flow reactor equipped with active mixing that was designed to handle those challenging continuous processes, such as the continuous formation of a Grignard reagent from a magnesium powder slurry.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 6","pages":"433-440"},"PeriodicalIF":1.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cristina Lía Fernández Regueiro, David Roura Padrosa
Flow biocatalysis combines the superior selectivity and sustainability of enzymes with the flexibility, automation potential, and enhanced productivity of continuous manufacturing. However, to apply a biocatalytic step in flow, some intrinsic limitations of biocatalysts must be addressed, especially their stability and reusability. Thus, enzyme immobilization is a key enabling technology and remains a critical step and one of the main bottlenecks. Immobilizing enzymes on solid supports improves their stability, reusability, and compatibility with flow conditions, but it is limited by the trial-and-error approach at the development stages. In this short perspective, we discuss recent innovations in enzyme immobilization, including in silico design, the combination with 3D printing and high-throughput screening, and present selected examples of applications in flow of immobilized enzymes, with a particular focus on process flexibility and their combination into chemoenzymatic cascades.
{"title":"Unlocking the Potential of Flow Biocatalysis with Enzyme Immobilization.","authors":"Cristina Lía Fernández Regueiro, David Roura Padrosa","doi":"10.2533/chimia.2025.411","DOIUrl":"10.2533/chimia.2025.411","url":null,"abstract":"<p><p>Flow biocatalysis combines the superior selectivity and sustainability of enzymes with the flexibility, automation potential, and enhanced productivity of continuous manufacturing. However, to apply a biocatalytic step in flow, some intrinsic limitations of biocatalysts must be addressed, especially their stability and reusability. Thus, enzyme immobilization is a key enabling technology and remains a critical step and one of the main bottlenecks. Immobilizing enzymes on solid supports improves their stability, reusability, and compatibility with flow conditions, but it is limited by the trial-and-error approach at the development stages. In this short perspective, we discuss recent innovations in enzyme immobilization, including in silico design, the combination with 3D printing and high-throughput screening, and present selected examples of applications in flow of immobilized enzymes, with a particular focus on process flexibility and their combination into chemoenzymatic cascades.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 6","pages":"411-416"},"PeriodicalIF":1.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maurice Moll, Björn Wängler, Carmen Wängler, Thorsten Röder
In the pharmaceutical industry, efficient, fast, and cost-effective API manufacturing processes are crucial for maintaining competitiveness. However, traditional production methods are often dominated by multi-purpose batch processes and empirical development approaches. This study presents the design and development of a fully automated, mL-scale continuous flow process for the asymmetric hydrogenation of benzylphenylephrone to (R)-benzylphenylephrine (BPE). The process employs a rhodium-based homogeneous catalyst under high pressure (up to 65 bar), achieving conversions of >96%, yields of up to 95% and high enantiomeric excess (ee) of up to 91%, with residence times of less than five minutes and a molar substrate to catalyst ratio (S/C) of 750. Kinetic investigations were conducted in a continuous flow microreactor, resulting in the development of a kinetic model that closely matches experimental data.
{"title":"Kinetic Investigation of the Asymmetric Hydrogenation of Benzylphenylephrone in Continuous Flow.","authors":"Maurice Moll, Björn Wängler, Carmen Wängler, Thorsten Röder","doi":"10.2533/chimia.2025.441","DOIUrl":"https://doi.org/10.2533/chimia.2025.441","url":null,"abstract":"<p><p>In the pharmaceutical industry, efficient, fast, and cost-effective API manufacturing processes are crucial for maintaining competitiveness. However, traditional production methods are often dominated by multi-purpose batch processes and empirical development approaches. This study presents the design and development of a fully automated, mL-scale continuous flow process for the asymmetric hydrogenation of benzylphenylephrone to (R)-benzylphenylephrine (BPE). The process employs a rhodium-based homogeneous catalyst under high pressure (up to 65 bar), achieving conversions of >96%, yields of up to 95% and high enantiomeric excess (ee) of up to 91%, with residence times of less than five minutes and a molar substrate to catalyst ratio (S/C) of 750. Kinetic investigations were conducted in a continuous flow microreactor, resulting in the development of a kinetic model that closely matches experimental data.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 6","pages":"441-448"},"PeriodicalIF":1.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemistry and biotechnology played a central role in transforming a poverty-stricken region in the middle of Europe into a flourishing industrial country. Rural areas remained destitute well into the 18th century. However, during the second half of the 18th century the foundation of the chemical powerhouses was laid. The biotechnological sector was built on these strong fundaments. This paper describes the development of the Swiss biotechnology sector from the early beginnings in the 1930s with a biocatalytic step in Vitamin C production to today's multifaceted application of biotechnology in Switzerland. As a matter of fact, biotechnology has become a key asset of the contemporary Swiss economy, and this paper outlines what is needed to stay on a successful path.
{"title":"Biomanufacturing in Switzerland - Past, Present, and Future.","authors":"Michael Altorfer, Jan M Lucht, Hans-Peter Meyer","doi":"10.2533/chimia.2025.292","DOIUrl":"https://doi.org/10.2533/chimia.2025.292","url":null,"abstract":"<p><p>Chemistry and biotechnology played a central role in transforming a poverty-stricken region in the middle of Europe into a flourishing industrial country. Rural areas remained destitute well into the 18th century. However, during the second half of the 18th century the foundation of the chemical powerhouses was laid. The biotechnological sector was built on these strong fundaments. This paper describes the development of the Swiss biotechnology sector from the early beginnings in the 1930s with a biocatalytic step in Vitamin C production to today's multifaceted application of biotechnology in Switzerland. As a matter of fact, biotechnology has become a key asset of the contemporary Swiss economy, and this paper outlines what is needed to stay on a successful path.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 5","pages":"292-298"},"PeriodicalIF":1.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Scientific and technological advances have created new biomanufacturing opportunities by overcoming manufacturing challenges and problems in various industrial sectors step by step and thereby lead to sustainable value creation. Bottom-up biomanufacturing approaches can provide value to customers in a competitive environment and when located in a geographically well-connected ecosystem bring additional benefits, such as derisking of supply chains, reduction of complexity, or strategic autonomy. The strategic importance of biomanufacturing can also be seen by different top-down initiatives and platforms addressing common critical needs.
{"title":"Biomanufacturing as Key Technology for a Sustainable Bioeconomy.","authors":"Roland Wohlgemuth","doi":"10.2533/chimia.2025.352","DOIUrl":"https://doi.org/10.2533/chimia.2025.352","url":null,"abstract":"<p><p>Scientific and technological advances have created new biomanufacturing opportunities by overcoming manufacturing challenges and problems in various industrial sectors step by step and thereby lead to sustainable value creation. Bottom-up biomanufacturing approaches can provide value to customers in a competitive environment and when located in a geographically well-connected ecosystem bring additional benefits, such as derisking of supply chains, reduction of complexity, or strategic autonomy. The strategic importance of biomanufacturing can also be seen by different top-down initiatives and platforms addressing common critical needs.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 5","pages":"352-358"},"PeriodicalIF":1.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ulla Létinois, Steven Crump, Bastian Zerrer, Michael Hans, Pierre-Bertrand Meunier, Markus Wyss
To restrict global warming to a maximum of 1.5 °C, greenhouse gas emissions need to be reduced to 'net zero' by 2050. The transition from the current, largely fossil-based global economy towards a circular, nowaste (bio-) economy based on renewable raw materials is seen as a critical pillar. In this paper, we explore the sustainability benefits as well as the implementation opportunities and challenges in Europe for three biomanufactured products used in animal and human nutrition, i.e. vitamins A and B2 and canthaxanthin. To allow the biomanufacturing industry to leverage its full potential and to achieve 'net zero' in time, it will be crucial for European policy makers to create the appropriate framework conditions for incentivizing the required transformation of the chemical sector as well as for securing the competitiveness of European industry.
{"title":"Way Forward for Biomanufacturing and Biotechnology in Europe.","authors":"Ulla Létinois, Steven Crump, Bastian Zerrer, Michael Hans, Pierre-Bertrand Meunier, Markus Wyss","doi":"10.2533/chimia.2025.344","DOIUrl":"https://doi.org/10.2533/chimia.2025.344","url":null,"abstract":"<p><p>To restrict global warming to a maximum of 1.5 °C, greenhouse gas emissions need to be reduced to 'net zero' by 2050. The transition from the current, largely fossil-based global economy towards a circular, nowaste (bio-) economy based on renewable raw materials is seen as a critical pillar. In this paper, we explore the sustainability benefits as well as the implementation opportunities and challenges in Europe for three biomanufactured products used in animal and human nutrition, i.e. vitamins A and B2 and canthaxanthin. To allow the biomanufacturing industry to leverage its full potential and to achieve 'net zero' in time, it will be crucial for European policy makers to create the appropriate framework conditions for incentivizing the required transformation of the chemical sector as well as for securing the competitiveness of European industry.</p>","PeriodicalId":9957,"journal":{"name":"Chimia","volume":"79 5","pages":"344-351"},"PeriodicalIF":1.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}