Flow chemist enhances drug synthesis to assist medical treatments
Published on 09 Mar 2022

Many people imagine chemists as goggle-adorned scientists swirling round-bottom flasks. However, this is not the case with Dr Wai Chung Fu (Croucher Fellowship 2018) and his chemistry lab, where he is pioneering the use of automated robotic technology.

He is using such technology to explore and improve the synthesis of pharmaceutical drugs to enable treatments, including a major drug used to treat different cancers, to be produced more efficiently and reduce costs. Repurposing greenhouse gases to assist drug synthesis is another key endeavour.

Fu, a research assistant professor at Hong Kong Polytechnic University, is interested in utilising and advancing the burgeoning new field of chemistry known as flow chemistry. Traditionally, chemical synthesis involves many steps carried out one after the other. At each step, a chemist must manually carry out the reaction and perform other procedures such as purification and compound characterisation. This requires a lot of hands-on time and is prone to human error.

In contrast, flow chemistry aims to carry out chemical reactions continuously by flowing reagents through a series of temperature-controlled channels or tubes. The process is completely automated, making it more reproducible and less error-prone than manually performed chemical reactions.

The continuous flow of reagents allows the system to mix or heat reagents efficiently due to the narrow channels and higher surface-area-to-volume ratio. It is also much faster and easier to scale up than traditional methods, which are typically limited by the mixing efficiency of larger batches. Furthermore, flow is safer as it requires smaller amounts of hazardous chemicals to be reacting at any given time.

Fu moved into the area of flow chemistry in 2018, after completing his PhD at PolyU and receiving a Croucher Fellowship to fund his postdoctoral research in Professor Timothy Jamison’s laboratory at the Massachusetts Institute of Technology in the US.

At PolyU he had worked under Croucher Foundation alumnus, Professor Fuk Yee Kwong (Croucher Fellowship 2000 and Croucher Senior Research Fellowship 2013), with his dissertation research revolving around palladium chemistry.

Palladium is an element that can catalyse chemical bond formations, and is commonly used by pharmaceutical companies to synthesise small molecule drugs. However, these reactions can be difficult to activate for certain molecules. Fu designed and synthesised new catalysts to promote palladium reactions, which could eventually facilitate better synthetic methodologies for drug manufacturing.

In the US, Fu applied flow chemistry to improve the synthesis of imatinib. Imatinib, known by its trade name Gleevec®, among others, is a drug used for treating many forms of cancer. Traditional methods for imatinib synthesis require a six-step process that takes more than 50 hours to complete. Fu designed a new synthetic route using only three steps and automated the entire process using flow.

This allowed him to synthesise imatinib in less than 50 minutes while greatly reducing human labour, energy costs, waste generation, and potential errors. Fu’s research could potentially enable pharmaceutical companies to efficiently manufacture large amounts of drugs, thereby reducing the cost of treatment. The findings were published, with Jamison, in 2019 in Organic Letters. Their paper was later highlighted in Synfacts, a journal that selects the most significant results in synthetic organic chemistry.

Fu went on to attempt another enterprising experiment: using a greenhouse gas to produce pharmaceutical ingredients.

He focused on HCFC-22, a gas that was once commonly used as a refrigerant in air conditioners. Nowadays, HCFC-22 is banned in most developed countries due to its detrimental effects on the ozone layer. Fu wondered if he could use HCFC-22, now a useless waste product, to extract reagents that could be employed in drug synthesis. HCFCs are the only greenhouse gas to contain fluorine, a valuable resource for drug synthesis, and HFCF-22 in particular is cheap to produce.

Flow chemistry was ideal for this context because carrying out traditional chemical reactions with gases is difficult. It requires a high-pressure instrument called an autoclave and often has low efficiency. In contrast, introducing gases directly to a flow chemistry micro-reactor is a relatively simple and efficient process. Previously improbable reaction conditions could also be enabled by using flow chemistry techniques.

Fu developed a new organic reaction and built a flow chemistry system to extract fluorine from HCFC-22. More than 20 per cent of drug molecules contain fluorine, as this chemical element can increase a drug’s stability, binding interactions, or ability to pass through cell membranes. Thus the ability to extract valuable fluorine from a former waste product was born from Fu’s flow chemistry technology.

The work was published in mid-2020, again with Jamison, in Angewandte Chemie International Edition. This work was also highlighted in Synfacts, and additionally selected as “Synfact of the Month”.

What drew Hong Kong-born Fu to chemistry in the first place? His fascination with the subject was initially sparked by his high school chemistry teacher. “He was so passionate about teaching,” Fu recalled. “It’s part of why I wanted to become a professor.”

He went on to study chemistry at Hong Kong Baptist University, where his research focused on using DNA-based analytical assays to detect proteins and metal ions. Fu published an impressive seven papers during his undergraduate career.

Now as he begins setting up his own independent lab as a PolyU academic, Fu is interested in combining his past experiences in palladium reactions, synthetic methodologies, and flow chemistry. He is particularly excited about using flow chemistry to extract useful reagents from other greenhouse gases, including fluoroform, sulphur hexafluoride, and carbon dioxide – and, through his technological advances, to help them gain a positive new purpose.

“We envision that our technology could eventually be used in greenhouse gas recycling facilities,” Fu said. “Flow chemistry systems are readily scalable, have a small footprint, and are plug and play. People with little to no chemistry background could operate these computer-controlled systems. It’s perfect for this purpose.”

Dr Wai Chung Fu joined Hong Kong Polytechnic University (PolyU) in 2020 as Research Assistant Professor in the Department of Applied Biology and Chemical Technology. He received his BSc in Chemistry from Hong Kong Baptist University in 2013, and his PhD from PolyU in 2018 before undertaking postdoctoral studies at MIT in the US. He was selected as a SciFinder Future Leader by Chemical Abstracts Service (under the American Chemical Society) in 2017. He received a Croucher Fellowship in 2018.

Extended Reading:

  1. Dr Fu’s personal profile (The Croucher Foundation): https://scholars.croucher.org.hk/scholars/wai-chung-fu
  2. Dr Fu’s personal profile (The Hong Kong Polytechnic University): https://www.polyu.edu.hk/abct/people/academic-staff/dr-fu-wai-chung/
  3. The scientific paper Dr Fu published in Organic Letters in 2019: https://pubs.acs.org/doi/10.1021/acs.orglett.9b02259
  4. The scientific paper Dr Fu published in Angewandte Chemie International Edition in 2020: https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202004260