Making new medicines often relies on getting the right molecules to stick together — and that’s not always easy. At Pomona College, chemistry professor Nicholas Ball and his students are finding smarter, cleaner ways to do just that. Ball’s lab, which includes several undergraduate researchers, is showing that meaningful scientific breakthroughs can happen right here on campus.
Ball’s lab is developing a method that could change how scientists create sulfur-containing compounds. These new reactions can make it faster, cheaper and more sustainable to produce molecules that show up in everything from antibiotics to cancer treatments. The approach uses metal catalysts, substances that speed up reactions without being consumed, to help form bonds between sulfur and nitrogen atoms.
“I have always been fascinated by how chemists make molecules to affect human health,” Ball explained in an email to TSL. His inspiration came from a 2014 paper by two-time Nobel Prize winner K. Barry Sharpless on sulfur-fluoride exchange (SuFEx). Ball saw this technique as “a new way to make sulfur-based compounds often seen in drug molecules — in particular those with S[ulfur]–N[itrogen] bonds.”
This matters because these compounds are the backbone of many common antibiotics, anticonvulsants and other therapeutics. Current methods to create these bonds use starting materials with undesirable side reactions. Ball’s team believed SuFEx could create these crucial S-N bonds “from air and water stable precursors [with] higher yield and less side products.”
A Breakthrough in Efficiency
In the world of chemistry, catalysts are like matchmakers — they bring molecules together without getting consumed in the process. But when these matchmakers cost Ball’s lab $44,000 per mole (a price that has now risen to over $82,000), chemists like Ball need to get creative.
The key innovation involves using what chemists call Lewis acids as a catalyst. These compounds are hungry for electrons and help speed up chemical reactions. In older methods, chemists had to use large amounts of expensive calcium compounds to make these reactions work. But Ball’s new approach, incorporating Lewis acids, uses a tenth of the catalyst.
“Catalysts are very useful in lowering the energy requirement for a reaction to occur. Importantly, you get the catalyst back after each transformation!” Ball wrote in the email. “The catalyst can also be very expensive, so using less of it saves material and money.”
In their recent paper, “Lewis Acid-Catalyzed Sulfur Fluoride Exchange,” Ball’s lab demonstrated that their method could create various sulfur-nitrogen compounds with yields as high as 99 percent. These compounds, known as sulfonamides, sulfamates and sulfamides, form the backbone of many important molecules used in medicine.
“At Pomona College, chemistry professor Nicholas Ball and his students are finding smarter, cleaner ways to do just that.“
The Silicon Solution
Beyond using less catalyst, Ball’s team also expanded the scope of starting materials that work in these reactions. They showed that compounds called silyl amines are particularly effective partners.
The innovation came from solving a fundamental problem. “After making an S–N bond, the calcium catalyst could not be regenerated,” Ball explained. “We believed this was because we were forming a strong calcium-fluorine bond, which made our catalyst inactive.”
Their elegant solution was to introduce silicon atoms through silyl amines. “Silicon has a stronger bond to fluorine,” Ball explained. This prevents the unwanted calcium-fluoride bond from forming, allowing the catalyst to be regenerated over the course of the reaction and used again.
This silicon strategy had multiple benefits: “Using Si[lyl]-amines allowed our reaction to go faster and it allowed us to be able to use other Lewis acids like those with lithium ions,” Ball said. The lithium-based catalyst costs just a tenth of the calcium version.
From Lab to Real-World Impact
While their new research is promising, there’s still work to be done before this approach becomes commonplace in industrial settings. But the potential benefits of reducing costs and waste while making important chemical building blocks could be substantial.
“Anytime we have more tools to make compounds, the more we can discover,” Ball said. “We hope our chemistry serves as a new, helpful tool.”
The findings could particularly benefit pharmaceutical research, where efficient methods to create diverse sulfur-containing compounds can accelerate drug discovery.
What’s Next?
Ball’s research continues to evolve.
“We have a whole pipeline of projects, including those that use machine learning,” he said. His team is exploring new catalysts to break bonds with sulfur compounds and looking to combine SuFEx with other reactions “to quickly get to complex molecules in an efficient manner.”
Ball emphasizes the value of undergraduate involvement in cutting-edge chemistry: “The privilege of having undergraduate students engage in research where they have ownership of their work is where I see my greatest impact. I am constantly inspired and amazed at the work they do!”
Through innovative chemistry and dedicated mentorship, Ball’s lab is proving that transformative scientific research doesn’t just happen at major research institutions — it’s thriving right here on campus.
Gabriel Brenner PO ’26 loves communicating science.
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