CAREER: Synthetic Models of Nitrile Hydratase to Elucidate Electronic and Second Coordination Sphere Effects

职业：用于阐明电子和第二配位球效应的腈水合酶的合成模型

• 批准号: 0238137
• 负责人: Craig Grapperhaus
• 金额: $ 48万
• 依托单位: University of Louisville Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0238137&HistoricalAwards=false
• 关键词: CAREER; Synthetic; Models; Nitrile; Hydratase

This award by the Inorganic, Bioinorganic and Organometallic Chemistry program supports research by Prof. Craig A. Grapperhaus at the University of Louisville to evaluate the potential roles of sulfur site oxygenation in the enzyme nitrile hydratase. This enzyme catalyzes the hydration of nitriles to amides by using iron in a non-redox role. A series of complexes that: (1) serve as an effective structural and electronic mimic of the active site, (2) contain two thiolate sulfurs cis to the substrate binding site that are reactive with oxygen, and (3) are easily modified with respect to the exogenous, sixth ligand and incorporation of second-coordination sphere functionalities on the ligand framework will be developed. If successful, this study will not only further the understanding of nitrile hydratase leading to the design of functional mimics, but will also serve the fundamental goal of developing and understanding sulfur-site reactivity and its ramifications on the properties and reactivity of a coordinated metal. The educational goals are focused on increasing undergraduate research participation as a means to increase student retention, graduation rates, and interest in graduate school in this traditionally under-performing region. This approach focuses on four key components: a formal Undergraduate Research Mentor Program to address local concerns, a regional, annual undergraduate research symposium, the involvement of undergraduate students in the proposed research and outreach to regional undergraduate institutions through site visits each semester. This research focuses on the design of metal complexes to understand sulfur-site reactivity in an important enzyme. This will aid the development of functional models for the industrially and environmentally important conversion of nitriles to amides. The project will also increase the participation of undergraduates in research as a way to increase student interest in science.

该奖项由无机，生物无机和有机化学计划支持研究教授克雷格A。Grapperhaus在路易斯维尔大学的研究，以评估硫位点氧化在腈水合酶中的潜在作用。 这种酶通过使用铁以非氧化还原作用催化腈水合为酰胺。 一系列复合物：（1）充当活性位点的有效结构和电子模拟物，（2）含有两个与氧反应的底物结合位点顺式的硫醇盐硫，和（3）相对于外源性第六配体容易修饰，并且将开发在配体框架上掺入第二配位球官能团。 如果成功的话，这项研究不仅将进一步了解腈水合酶导致功能模拟物的设计，但也将服务于开发和理解硫位点反应性及其对配位金属的性质和反应性的影响的基本目标。 教育目标的重点是增加本科生的研究参与，以提高学生的保留率，毕业率和在这个传统上表现不佳的地区研究生院的兴趣。 这种方法的重点是四个关键组成部分：一个正式的本科生研究导师计划，以解决当地的关注，区域，年度本科生研究研讨会，本科生参与拟议的研究和推广到区域本科院校通过每学期的实地考察。本研究的重点是金属配合物的设计，以了解在一个重要的酶的硫位点的反应。 这将有助于开发功能模型的工业和环境重要的腈转化为酰胺。 该项目还将增加本科生对研究的参与，以提高学生对科学的兴趣。