This work introduces a technique for using hydrogen and electricity to create pharmaceuticals. Hydrogen can be made using renewable energy sources such as solar power, making the process more sustainable. (Image: UW–Madison)

In a new study, University of Wisconsin–Madison chemists and engineers demonstrate one potential path toward greener ways to make chemicals: By adapting hydrogen fuel cell technologies, which are already used to power some EVs, laptops, and cell phones.

“The chemical industry is a massive energy consumer, and there is a big push to decarbonize the industry,” said Professor Shannon Stahl, who guided much of the research. “Renewable electricity can provide energy to produce chemicals with a much lower carbon footprint than burning fossil fuels.”

The study uses electricity to overcome a complementary challenge. An important new process for making drugs requires large quantities of zinc metal as a source of electrons. However, handling zinc is complicated and generates large amounts of environmentally unfriendly waste. Working with scientists at the pharmaceutical maker Merck & Co. Inc., the team sought to develop a more sustainable method to manufacture ingredients needed to make many types of drugs.

They took inspiration from hydrogen fuel cells, which use hydrogen gas as the source of electrons to generate electricity.

“The process we are working with needs a green source of electrons,” said Stahl. “We realized that fuel cell technology could be modified to make chemicals rather than electricity.”

Shannon Stahl (Image: UW–Madison)

Hydrogen gas is an ideal choice in many ways, according to Stahl. It can be generated from renewable electricity, and it creates very little waste. Developing a hydrogen-based way to make pharmaceuticals aligns with renewed interest in a “hydrogen economy.”

“This work is connected to a broader effort to create a hydrogen infrastructure that goes beyond fuel cells and energy production,” said study lead Mathew Johnson. “This work shows that hydrogen can be combined with electricity to make new drugs.”

The researchers developed a system that uses a type of organic compound called a quinone to pull electrons away from hydrogen. An important feature of this process is that it works well in the absence of water. The system then uses electricity to supercharge the electrons, giving the electrons more energy than hydrogen could normally provide.

The work, published in Nature, shows how it can be used to make dozens of important organic molecules, including a large batch of a pharmaceutical ingredient. The team is now working to improve the process so it can be used for industrial-scale production. And Stahl and his collaborators see even bigger opportunities for this technology.

“This is a broadly applicable technology for chemical production,” said Johnson. “Many chemical processes need electrons. This is not limited to pharmaceuticals. It should be a very versatile technology.”

Here is a Tech Briefs interview with collaborative answers from Stahl and Johnson.

Tech Briefs: I’m sure there were too many to count, but what was the biggest technical challenge you faced while developing this approach?

Stahl/Johnson: The biggest technical challenge we needed to address in this work was identifying a “green” source of electrons for this new/important class of reactions for pharmaceutical synthesis. The conventional methods use Zn metal powder, which is difficult to handle and creates a lot of waste. Hydrogen is an ideal source of electrons as it is the most widely used “reductant” (source of electrons) in the chemical industry.

Mathew Johnson (Image: UW–Madison)

But, hydrogen has two problems: (a) it is not a strong enough reductant to do the job for the chemical reactions we were doing and (b) electrochemistry can solve the first problem, but there are not good methods to obtain electrons from hydrogen under non-aqueous conditions using electrochemistry (our reactions require non-aqueous conditions).

As a secondary technical issue, hydrogen is a source of both electrons and protons. In many applications that need electrons, the protons are also needed (as in hydrogenation reaction — think, partially hydrogenated oils in food). In our case, the protons are problematic. We had to create a system that could take the electrons without the protons from hydrogen. We succeeded.

Tech Briefs: Can you explain in simple terms how it works?

Stahl/Johnson: The inspiration here was prompted by the challenge noted above that electrons are not easy to obtain directly from hydrogen using electrochemistry in non-aqueous solvent. We recognized that this problem could be solved by combining two well-established phenomena: (a) hydrogenation of organic molecules in non-aqueous solvent is simple, and this process could be used to convert quinones to hydroquinones, and (b) hydroquinones undergo facile electrochemical oxidation in non-aqeuous solvent. By combining these two concepts we are able to use H2 in combination with a quinone “mediator” in an electrochemical cell to access electrons from H2for our reaction.

For some additional context: “electro” specifies that the energy for the reaction is traveling through an electric circuit, while “mediated” means that there will be some sort of intermediary molecule between that contributes to the transfer of electrons from the molecule of interest (in this case, H2) and the electrode.

Tech Briefs: It’s been said that “The team is now working to improve the process so it can be used for industrial-scale production.” How is that coming? Any updates you can share?

Stahl/Johnson: There are many opportunities for further development — one of the first is to achieve higher current densities that could support reactions that will be conducted on scales larger than pharmaceuticals. We have been quite successful in recent work, accessing rates (i.e., current densities) that are more than an order of magnitude higher than we used in the initial study.

Tech Briefs: It has also been said, “And Stahl and his collaborators see even bigger opportunities for this technology.” While Johnson is quoted as saying, “This is a broadly applicable technology for chemical production. Many chemical processes need electrons. This is not limited to pharmaceuticals. It should be a very versatile technology.” Can you elaborate on that please?

Stahl/Johnson: We would love to explore whether our technology could support the nitrogen reduction to make ammonia. This process has been claimed to account for 1.4 percent of global carbon dioxide emissions and consumes 1 percent of the world’s total energy production. Using electricity to drive ammonia production could have major impacts, and this technology could play a role in that process.

Tech Briefs: Do you have any advice for engineers aiming to bring their ideas to fruition?

Stahl/Johnson: I’m not an engineer, so my advice would be to “work with chemists.” We have really benefited from our interactions with engineers, but we find relatively few engineers willing to learn our language and being patient enough with us to help us learn their language. Ultimately, we would benefit from much more cross-talk and interaction.