Oxidative stress damages cells and is tied especially to heart disease and cancer, as well as Alzheimer's and Parkinson's disease. Separate portions of the research were detailed in proof-of-concept papers in the Journal of the American Chemical Society in June and in November in Angewandte Chemie, an international journal. "We have discovered that small organic molecules can be engineered to release a molecule called carbonyl sulfide, which is the most prevalent sulfur-containing molecule in the atmosphere, but more importantly converts rapidly to hydrogen sulfide under biological conditions," said Michael Pluth, a professor of chemistry and co-author on both papers. "We developed and demonstrated a new mechanism to release small molecules that provide therapeutic hydrogen sulfide." Hydrogen sulfide, a colorless gas, has long been known for its dangerous toxicity—and its telltale smell of rotten eggs—in the environment, but it also is produced in mammals, including humans, with important roles in molecular signaling and cardiac health. Initially, Pluth's doctoral student Andrea Steiger, lead author of the ACS paper, used benzyl thiocarbamates to design responsive organic molecules that release carbonyl sulfide. For the second paper, postdoctoral researcher Yu Zhao, also in Pluth's lab, adapted the molecule so it remains nontoxic and stable until cellular conditions trigger it to release the carbonyl sulfide, which is converted to hydrogen sulfide by carbonic anhydrase enzymes in the body. Finding a way to generate restorative hydrogen sulfide in the body has been a goal of many research labs around the world in the last two decades. Researchers in Pluth's lab in 2013 developed a probe that detects the gas in biological samples, providing a framework to test potential donor molecules, either synthetically produced or isolated from natural products. "To do that we need to develop new chemistry," Pluth said.

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