Metal Coordination and DNA Interactions Control Sulfur and Selenium Antioxidant Mechanisms

生物系统中天然存在的铁离子和铜离子会产生破坏DNA的自由基。控制这种损害是至关重要的。硫酮和硒的抗氧化剂分别含有硫和硒，可以通过结合铁和铜离子来防止DNA损伤。关于硫酮和硒与金属离子结合产生抗氧化活性的具体方式，或者这些抗氧化剂或其金属络合物如何与DNA相互作用以防止自由基损伤，人们知之甚少。通过这一奖项，化学部生命过程化学项目资助克莱姆森大学的Julia Brumaghim博士研究硫和硒抗氧化剂如何防止DNA损伤。拟议的研究促进了对细胞自由基损伤及其预防的理解。这些调查也为跨学科的研究生和本科生培训提供了机会。布鲁马吉姆博士通过设计一项关于使用茶叶抗氧化剂预防DNA损伤的探究驱动的实验室实验，为初中和高中教师和学生的教育做出了贡献。Brumaghim的研究集中在一类独特的硫和硒抗氧化剂上，这些抗氧化剂的生物学作用是至关重要的，但人们对其了解很少，即硫酮和硒。对这些分子及其生物相关金属络合物的氧化还原行为的研究导致了可能适用于包含相同官能团的各种生物活性分子的信息。与被广泛研究的只防止铜介导的DNA损伤的硫和硒氨基酸相反，硫酮和硒抗氧化剂防止铁比铜造成的DNA损伤更多。本研究考察了这两种抗氧化剂与Fe(II)和Cu(I)的配位化学，试图阐明它们与含硫和含硒氨基酸的活性差异。这项研究还提供了硫酮和硒酮防止DNA损伤的潜在分子机制的信息。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.