New Biologically Relevant Sulfur Radical Cation Chemistry

新的生物学相关硫自由基阳离子化学

• 批准号: 0455575
• 负责人: Richard Glass
• 金额: $ 36.9万
• 依托单位: University of Arizona
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-15 至 2008-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0455575&HistoricalAwards=false
• 关键词: New; Biologically; Relevant; Sulfur; Radical

The Organic and Macromolecular Chemistry Program supports Professor Richard S. Glass at the University of Arizona who proposes to examine the chemical basis for the hypothesis that the pathogenesis of Alzheimer's disease involves oxidation. It is proposed that Met-35 of beta-amyloid peptides was responsible for initiating this oxidation by reducing metal ions, i.e. Fe(III) or Cu(II), which then participate in Fenton-type reactions to generate the potent oxidant OH radical. The proximity of an amide or phenyl ring to the Met sulfur was invoked to lower the oxidation potential of the sulfur by promoting electron-transfer generating a sulfur radical cation.Professor Glass will examine neighboring group participation by amide and aromatic rings on electron transfer from thioethers specifically assessing the nature of bonding in these unique systems. To accomplish these goals a combination of methods will be used: (1) design and synthesis of conformationally constrained molecules, (2) electrochemical studies, (3) pulse radiolysis studies, (4) electron paramagnetic resonance (EPR) spectroscopic studies, (5) photoelectron spectroscopy (PES) studies and (6) computational studies (theoretical calculations). The use of such diverse methodologies will require the collaboration of several laboratories. In addition to uncovering novel chemistry, the proposed studies should provide insight and tools for evaluating the basis for Alzheimer's disease.The Organic and Macromolecular Chemistry Program supports Professor Richard S. Glass whose proposed studies will involve undergraduate, graduate and postdoctoral students as well as collaborations with the University of Kansas, Notre Dame University and Arizona State University. Indeed a unique multi-institutional consortium will be empowered to address fundamental chemical questions with a wide array of potent methods and expertise. The proposed work may lead to an understanding of the chemical basis of Alzheimer's disease. Such an understanding may result in improved diagnosis or treatment for this devastating disease, which is a major health problem currently in the U.S. and increasing with the aging population.

有机和高分子化学项目支持亚利桑那大学的理查德·S·格拉斯教授，他建议检验阿尔茨海默病的发病机制涉及氧化的假说的化学基础。有人认为，β-淀粉样多肽中的Met-35通过还原金属离子，即Fe(III)或Cu(II)，参与Fenton类型的反应，产生强有力的氧化剂OH自由基，从而启动这种氧化。利用酰胺或苯环与甲硫醚的接近，通过促进电子转移产生硫自由基阳离子来降低硫的氧化电位。格拉斯教授将研究酰胺和芳香环对硫醚电子转移的邻近基团参与，具体评估这些独特体系中的成键性质。为了实现这些目标，将使用一系列方法：(1)构象受限分子的设计和合成，(2)电化学研究，(3)脉冲辐解研究，(4)电子顺磁共振(EPR)光谱研究，(5)光电子能谱(PES)研究和(6)计算研究(理论计算)。使用这种不同的方法将需要几个实验室的合作。除了揭示新的化学，建议的研究应该为评估阿尔茨海默病的基础提供洞察力和工具。有机和高分子化学项目支持理查德·S·格拉斯教授，他建议的研究将包括本科生、研究生和博士后，以及与堪萨斯大学、圣母大学和亚利桑那州立大学的合作。事实上，一个独特的多机构联合体将被授权用一系列强有力的方法和专业知识来解决基本的化学问题。这项拟议的工作可能有助于理解阿尔茨海默病的化学基础。这样的理解可能会改善对这种毁灭性疾病的诊断或治疗，这种疾病目前在美国是一个主要的健康问题，随着人口老龄化而增加。