As a result of this award from the Chemistry of Life Processes Program, Dr. Julia L. Brumaghim, from Clemson University, will study the molecular determinants of selenium antioxidant activity. Iron and copper-generated hydroxyl radical causes DNA damage and cell death under oxidative stress conditions, and controlling this damage is a vital cellular process. Selenium antioxidant treatment to prevent DNA damage is an active area of research, and multiple studies are yielding promising but often contradictory results that highlight the need for additional research into the fundamental mechanisms of selenium antioxidant activity. Dr. Brumaghim has recently established that selenium antioxidants prevent oxidative DNA damage by binding metal ions, preventing generation or release of damaging hydroxyl radical. The new project will investigate metal coordination as a novel selenium antioxidant mechanism and compare it to more traditional mechanisms of selenium antioxidant activity, such as glutathione peroxidase activity and reactive oxygen species scavenging. For this work, Dr. Brumaghim and her students will synthesize coordination complexes of selenium antioxidants with Fe2+ and Cu+ ions to determine how metal binding results in antioxidant activity, and quantify the ability of selenium antioxidants to inhibit copper-, iron-, and peroxynitrite-mediated DNA damage. This research represents the first systematic comparison of selenium antioxidant mechanisms from basic coordination chemistry to DNA damage studies, and the results of this research will extend the fields of coordination chemistry, oxidative damage, and selenium biochemistry.
In addition to the scientific advances this research represents, performing these studies will promote graduate and undergraduate student training in a broad variety of techniques related to the growing fields of inorganic and biological chemistry. It will also establish or expand research partnerships between Dr. Brumaghim and Profs. Craig Bayse (Old Dominion University), Pamela Riggs-Gelasco (College of Charleston), and R. Kenneth Marcus (Clemson University). Research results will be disseminated broadly through scientific publications and seminars at scientific conferences and universities, as well as through seminars for the general public. Dr. Brumaghim will also develop a summer teacher-training workshop on antioxidants and their ability to prevent DNA damage in conjunction with the South Carolina DNA Learning Center at Clemson University. This workshop will provide high school teachers with hands-on activities and state-of-the-art knowledge about the popular topic of antioxidants.