Going with the Flow

Interest in flow chemistry is on the rise, and the commercial availability of benchtop continuous flow instruments has driven widespread adoption of the technique for organic synthesis, drug discovery and development, biocatalysis and many more chemistry applications in both industry and academia. This month we sat down with Dr Omar Jina, Chief Commercial Officer at Syrris Ltd., to discuss flow chemistry, its applications and the push to raise awareness of this transformative technology. 

Laura Mason (LM): Could you tell us a little more about Syrris, the company’s mission and its goals?

Omar Jina (OJ): Syrris is part of the Blacktrace Group, which includes our sister companies Dolomite Microfluidics and Dolomite Bio. At Syrris, we specialize in developing easy-to-use, high performance equipment for both batch and continuous flow chemistry. We have a team of over 100 people, including a large proportion of scientists and engineers, and have won two prestigious R&D 100 Awards for our Asia flow chemistry system and the Fluidic Factory, a microfluidic 3D printer.

Our passion is making chemists’ lives easier, ensuring that our customers can spend time on accelerating their research. Syrris products are now being used in laboratories worldwide for a whole range of applications, from process development and discovery chemistry to crystallization and process scale-up. Our aim is to develop systems and solutions to help scientists tackle the environmental, economic and health challenges of the 21^st century.

LM: Not all of our readers will be familiar with flow chemistry. Could you tell us a little about it?

OJ: Flow chemistry goes by a number of names; your readers may have heard it referred to as plug flow, microchemistry or continuous flow chemistry. The easiest way to explain flow chemistry is to contrast it with batch chemistry, which is the traditional approach used by scientists for hundreds of years. Batch chemistry involves loading reagents into a single container – often a round bottom flask or jacketed reactor vessel – while heating and stirring to ensure the reaction proceeds to completion. This is then usually followed by separate steps to work up and purify the product. In contrast, in a flow chemistry regime, reagents are continuously pumped through a temperature-controlled tube or pipe; if the reagents are reactive, the reaction takes place and the product is generated. Due to a number of key factors – including reactor geometry, enhanced temperature control and rapid, efficient mixing – flow techniques offer excellent reaction control and, importantly, reproducible chemistry.

LM: What are some of the benefits of flow chemistry?

OJ: It’s important to say that flow chemistry is a complementary technique to batch chemistry and that not all reactions are worth translating from batch to flow. However, enormous benefits – too many to cover in any great detail – can be obtained for a large number of reactions. In short, for a many academic and discovery chemists, flow chemistry can enable reactions that cannot be performed using conventional techniques, opening up new chemical spaces and potentially leading to many new molecules being produced. This is evidenced by the vast growth in high quality academic papers published over the last five to 10 years. For development and large-scale chemists and chemical engineers, flow chemistry offers rapid process optimization and a much easier route to scale-up, creating a smoother transition from the lab to manufacturing, while the inherent increase in efficiency can lead to processes offering a much greater return on investment. In addition, flow chemistry offers far greater process safety, as much smaller amounts of material are reacting at any one time. For a more in-depth explanation, take a look at the blog post Why perform your chemistry in continuous flow.

LM: What role do flow chemistry systems play in sustainable chemistry?

OJ: That’s a broad question, so it might be helpful to hone in on one particular application – biocatalysis. This area is expanding rapidly to meet the increasing demand for biological ‘green’ alternatives to chemical catalysis, and flow chemistry offers a number of benefits that contribute towards a more sustainable future. For example, the amount of biocatalyst that can be used in a batch process is often dependent on the concentration and final volume of the reaction. Under continuous flow conditions, reagents and solvents can be passed through a packed bed column without limitation, maximizing exposure to the biocatalyst. This has a twofold benefit. A smaller amount of the biocatalyst needs to be used in the first place, and faster reaction times have the knock-on effect of reducing energy consumption. In addition, batch processes, unlike continuous flow reactions, typically require agitation to enable the reagents to mix thoroughly, and mechanical stirrers can often damage the biocatalyst surface, leading to a loss of catalytic activity and more of the biocatalyst being used.

LM: Could you tell us more about the role of flow chemistry in drug discovery and medicinal chemistry environments?

OJ: Flow chemistry can, and does, play a significant role in drug discovery, with the key benefit focused on speeding up discovery pipelines. Medicinal chemists do not typically require large volumes of product, usually just enough for characterization. Flow chemistry offers the capability to run much faster, sequential reactions, allowing a segmented flow approach for targeted library synthesis with automated reagent additions.

Flow chemistry can also open up the use of other techniques, such as photochemistry and electrochemistry. One application of flow electrochemistry that is certainly benefitting medicinal chemists is the synthesis of metabolites. Once a medicinal chemist has achieved a ‘hit’ compound, the candidate can be dissolved and pumped through the flow electrochemical cell to yield a range of selectively oxidized metabolites. This simple operation means that the chemist does not have to develop new synthetic pathways to produce the metabolites, potentially saving months of time.

As mentioned previously, there are also reactions that can be performed in flow that simply cannot be done in batch, and there are numerous publications reporting telescoping – or multi-step – reactions. An example of this might be a reaction performed at low temperature, say -40°C, to deprotonate a substrate, with the product of this reaction flowing straight into another reactor at 200°C, where you may want to add a nucleophile. This potentially opens the door for new molecules to be discovered, which is a very exciting prospect.

LM: Syrris’ resident flow chemistry expert Andrew Mansfield recently presented a series of ‘lightning talks’ at ACHEMA 2018. Can you tell us a little more about them?

OJ: We have a major drive to educate as many chemists as possible about flow chemistry. We have an ongoing worldwide program of free educational workshops to help chemists learn about flow, and gain hands-on experience to assist with its implementation. We had a great response to our lightning talks at ACHEMA 2018, where delegates learned about the technique and which processes are best performed in flow. Most importantly, they discovered a number of tips to help them to convert batch processes to continuous flow. A summary of the talks and supporting information can be found on our website and, if any of your readers would like any advice on the topic, we encourage them to contact us and speak to one of our team of applications chemists.

Dr Omar Jina was speaking to Laura Elizabeth Mason, Science Writer for Technology Networks.