CAREER: Advancing the Chemical Understanding of Reactive Sulfur Species Through Photoactivated Donors and Computational Tools

In this CAREER project, funded by the Chemical Mechanism, Function, and Properties Program of the Chemistry Division, Professor Pier Alexandre Champagne of the Department of Chemistry and Environmental Science at the New Jersey Institute of Technology is employing a combination of experimental and computational techniques to advance the chemical understanding of reactive sulfur species, which are of significant importance in biochemistry. The goal of this research is to access new synthetic donors of reactive sulfur species, use the donors to probe the behavior of those species, and apply computational tools to obtain a holistic understanding of their chemical reactivity. Regarding educational activities, the Visualize Organic Chemistry online learning platform will be expanded with new animations and tutorials that support greater mechanistic literacy among organic chemistry students and practitioners across the United States. Reactive sulfur species are a wide class of biochemical intermediates that have important physiological effects but that are still not well understood due to their thermodynamic and kinetic instability. The proposed computations will address this issue by characterizing the intrinsic reactivity of polysulfides with biological nucleophiles and electrophiles using Density Functional Theory calculations, allowing a holistic understanding of their behavior in vivo. The proposed synthetic donors of reactive sulfur species will provide access to new photoactivated tools to study the chemical reactivity and biochemical effects of reactive sulfur species, by leveraging the BODIPY photocage scaffold. These will enable the study of structural effects on persulfide reactivity, and the experimental characterization of the chemical properties of hydrotrisulfides, heralding a new era in the study of polysulfides that are critical to biochemistry. 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.