Professor Nicholas Ball

Professor Nicholas Ball
Department of Chemistry
Pomona College

Sulfur Fluoride Exchange (SuFEx) as a New Tool in Drug Discovery

Why are drugs so expensive? One reason is that it takes scores of researchers and resources to discover and make them. Sulfur(VI) compounds represent over 30% of all sulfur-based FDA- approved drugs. Their shared S–O double-bond architecture manifests in drug compounds with similar physiochemical properties and bioactivity profiles. Preferred synthetic routes to these molecules have remained unchanged since the discovery of “sulfa” drugs early in the 20th century and have several disadvantages. So, how can we better make these molecules? Sulfur fluoride exchange (SuFEx) chemistry is emerging as a promising synthetic tool in chemical biology, bioorganic, and medicinal chemistry. In synthesis, sulfur (VI) fluorides show great promise as building blocks in organic chemistry due to their increased stability compared to other sulfur (VI) halogen analogues. Over the past decade, innovations in synthesizing S(VI) fluorides have unlocked their potential for the development of bench- stable libraries of readily available precursors for derivatization in drug discovery. Key to the adoption of SuFEx chemistry is the development of efficient methods for synthesizing and reacting sulfur(VI) fluorides. This presentation will focus on the Ball group’s contributions to sulfur fluoride chemistry and their medicinal chemistry applications. New SuFEx methods that react a broad set of S(VI) fluorides with carbon, oxygen, and nitrogen-based nucleophiles towards structurally diverse S(VI) compounds will also be featured – unlocking new forms of S(VI) compounds with strong potential for biological activity. The presentation will also highlight the groups’ use of emerging tools in bioorganic, computational chemistry, high- throughput experimentation, and data science to inform the design and understanding of new reactions and the rapid creation of molecular libraries. The presentation will also feature accounts of how undergraduate researchers have led and driven projects with industrial and academic collaborators.

Nicholas Ball

Prof. Nicholas Ball grew up in Chattanooga, TN. He received his B.A. in Chemistry at Macalester College in 2005. He completed his Ph.D. in 2011 under Prof. Melanie Sanford at the University of Michigan, working on C–F and C–CF3 bond formation using high- oxidation-state palladium. In 2010, he headed to the California Institute of Technology to pursue his postdoctoral studies with Prof. David Tirrell as an NIH Postdoctoral Fellow. Prof. Ball started as an ssistant Professor at Amherst College in 2013. In 2015, Prof. Ball joined the faculty at Pomona College and is now an Associate Professor of Chemistry with tenure. His current research focuses on developing new methods to make and use sulfur-based molecules for drug targets, biological chemical probes, and materials science. His lab’s work involves making molecules, machine learning, and computational chemistry. His work features collaborations with industry and internationally, as well as with professors at other predominantly undergraduate institutions. Prof. Ball’s honors and awards include the Henry Dreyfus TeacherScholar Award, 2022 Chemical and Engineering News LGBTQ+ trailblazer, and a two-time Wig Distinguished Professor awardee (2018 and 2024). His research has been funded by NIH, NSF, and the American Chemical Society.

Hosted by Professor Courtney Roberts