Sulfane Sulfurs/SO2: Deciphering Redox Environments and Their Implications in Cardio-Protection

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Project Summary Redox imbalances between reactive sulfur species (RSS) and reactive oxygen species (ROS) in cardiac cells contribute to diseases such as ischemia/reperfusion (MI/R) injury and coronary artery disease. Re- establishing redox homeostasis has been found to cause strong cardioprotective effects such as vasodilation, antihypertension and antifibrosis. However, this field lacks clear chemical understandings as to how these systems work. Our long-term goal is to decipher the complicated redox pathways in various stages of cardiac cell health and use the information to advance cardiovascular therapies by re-establishing redox homeostasis. Specifically, this project will develop chemical tools that: 1) controllably mimic complex RSS redox environments focusing on sulfane sulfurs; and 2) simultaneously detect and utilize ROS to trigger sulfur dioxide (SO2)-related cellular insights and therapeutic advantages. A variety of these chemical tools will be synthesized, and their structure activity relationships will be optimized using published procedures. We will then explore their cardioprotective actions in cell models of MI/R injury and test their viabilities for deciphering complex cardiovascular redox pathways. We expect promising candidates will be identified for future evaluations in animal models of MI/R and heart failure. The outlined research will take place in Dr. Ming Xian’s chemical biology laboratory at Brown University. This research environment contains state-of-the-art tools and equipment for synthetic chemistry and biology.