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

该奖项由无机、生物无机和有机金属化学项目颁发，支持路易斯维尔大学Craig A. Grapperhaus教授的研究，以评估硫位点氧化在酶腈水合酶中的潜在作用。这种酶通过铁在非氧化还原作用下催化腈水合成酰胺。一系列的配合物，(1)作为有效的结构和电子模拟活性位点，(2)包含两个顺式硫代硫与底物结合位点，与氧反应，(3)很容易被外源的第六配体修饰，并在配体框架上结合第二配位球功能将被开发。如果成功，这项研究不仅将进一步了解腈水合酶，从而设计功能模拟物，而且还将服务于发展和理解硫位点反应性及其对配位金属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，作为提高学生保留率、毕业率和对这个传统上表现不佳地区研究生院兴趣的一种手段。该方法侧重于四个关键组成部分：一个正式的本科生研究导师计划，以解决当地关注的问题，一个区域，年度本科生研究研讨会，本科生参与拟议的研究，并通过每学期的实地考察向区域本科院校伸出援手。本研究的重点是设计金属配合物，以了解一种重要酶的硫位点反应性。这将有助于开发具有工业和环境重要性的将腈转化为酰胺的功能模型。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。

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.