New Biologically Relevant Sulfur Radical Cation Chemistry

有机和高分子化学计划支持教授理查德S。他提出要研究阿尔茨海默病的发病机制与氧化有关这一假说的化学基础。有人提出，β-淀粉样肽的Met-35负责通过还原金属离子，即Fe（III）或Cu（II），然后参与Fenton型反应以产生有效的氧化剂OH自由基来引发这种氧化。酰胺或苯环与Met硫的邻近性被调用，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。Glass教授将研究酰胺和芳环对硫醚电子转移的相邻基团参与，特别评估这些独特系统中的键合性质。为了实现这些目标，将使用以下方法的组合：（1）构象约束分子的设计和合成，（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。除了发现新的化学，拟议的研究应该提供洞察力和工具，评估阿尔茨海默病的基础。玻璃，其拟议的研究将涉及本科生，研究生和博士后学生，以及与堪萨斯大学，圣母大学和亚利桑那州州立大学的合作。事实上，一个独特的多机构联合体将被授权以各种有效的方法和专门知识来解决基本的化学问题。这项工作可能有助于了解阿尔茨海默病的化学基础。这样的理解可能会改善这种毁灭性疾病的诊断或治疗，这是美国目前的一个主要健康问题，并随着人口老龄化而增加。

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.