Metal Coordination and DNA Interactions Control Sulfur and Selenium Antioxidant Mechanisms

Clemson University, Clemson SC

Investigators

Abstract

Iron and copper ions naturally present in living systems can generate radicals that damage DNA. The control of this damage is vital. Thione and selone antioxidants, which contain sulfur and selenium, respectively, prevent DNA damage by binding iron and copper ions. Very little is known about the specific ways in which the binding of the thiones and selones to the metal ions results in antioxidant activity or how these antioxidants or their metal complexes interact with DNA to prevent radical damage. With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Julia Brumaghim from Clemson University to investigate how sulfur and selenium antioxidants prevent DNA damage. The proposed investigations advance the understanding of cellular radical damage and its prevention. The investigations also represent opportunities for interdisciplinary graduate and undergraduate student training. Dr. Brumaghim contributes to the education of middle and high school teachers and students by designing an inquiry-driven lab experiment about prevention of DNA damage using tea antioxidants. Dr. Brumaghim's research focuses on a unique class of sulfur and selenium antioxidants whose biological effects are vital but poorly understood, namely thiones and selones. The study of the redox behavior of these molecules and of their biologically-relevant metal complexes leads to information that may be applicable to a wide variety of bioactive molecules that contain the same functional groups. In contrast to widely studied sulfur- and seleno-amino acids that prevent only copper-mediated DNA damage, thione and selone antioxidants prevent more DNA damage from iron than from copper. This research examines the coordination chemistry of the two antioxidants with Fe(II) and Cu(I) in an effort to elucidate the differences between their activity and that of sulfur- and selenium- containing amino acids. The research produces also information on the molecular mechanism underlying the ability of thiones and selenones to prevent DNA damage. 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.