Expanding the Bio(in)organic Chemistry of Reactive Sulfur and Selenium Species

Researchers from the University of Oregon are developing new chemical tools to understand how biologically important sulfur and selenium compounds react and function in living systems. Sulfur and selenium are essential elements used by cells to build biomolecules, regulate oxidative stress, and support enzyme function, but many of their most important reactive forms are short-lived, difficult to observe, and challenging to control. These factors create a major barrier to understanding how cells use these elements relevant biomolecular regulation, which supports both basic science and biotechnology advancement. The research team will investigate and establish new mechanistic understanding of how these compounds react, helping to explain how sulfur and selenium chemistry is used across important biological pathways. The discoveries could provide molecular-level insights into antioxidant processes, selenium-dependent biomolecule assembly, and new chemical approaches to interact with sulfur- and selenium-dependent pathways. The anticipated results form a strong platform for biotechnology advances by enabling new ways to study, regulate, or engineer sulfur- and selenium-dependent biological pathways. The project will train undergraduate, graduate, and postdoctoral researchers in synthetic chemistry, spectroscopy, and chemical biology, while supporting hands-on science outreach for middle school students and practical guidance for maintaining continuity in academic chemistry laboratories. This research project seeks to establish the foundational chemistry needed to probe and manipulate different intermediates that control sulfur and selenium trafficking and reactivity. The work will focus on three integrated themes. First, thioselenide-based platforms will be used to define how molecular structure controls chalcogen transfer reactions, persistence, and reactivity. Second, new chemical approaches will be developed to investigate and manipulate selenophosphate, a central intermediate in selenoprotein biosynthesis. Third, coordination of persulfide and mixed sulfur/selenium species to Lewis-acidic metal sites will be examined to determine how binding interactions influence dichalcogenide stability and sulfur/selenium transfer. Mechanistic studies will combine synthetic chemistry, multinuclear NMR spectroscopy, kinetic analysis, and complementary cell-based experiments that assess toxicity and oxidative stress responses. Together, these studies will identify structural and electronic factors that control reactive sulfur and selenium intermediates and provide a chemical framework for probing chalcogen-dependent signaling, redox biology, and biomolecule assembly This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.