Oxygen Sensitivity and Functional Models of Nitrile Hydratase

腈水合酶的氧敏感性和功能模型

• 批准号: 0749965
• 负责人: Craig Grapperhaus
• 金额: $ 38.4万
• 依托单位: University of Louisville Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-15 至 2012-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0749965&HistoricalAwards=false
• 关键词: Oxygen; Sensitivity; Functional; Models; Nitrile

This award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports research by Professor Craig Grapperhaus at the University of Louisville that focuses on functional model complexes of nitrile hydratase (NHase) and the related oxygen sensitivity of iron thiolates. The project includes the synthesis and spectroscopic characterization of target complexes coupled with reactivity studies and computational methods to develop an understanding of the relationship between electronic structure and reactivity. The first specific aim is to test the hypothesis that functional NHase models mimic S-oxygenation effects including tuning of Lewis acidity and substrate activation/intermediate stabilization via a second coordination sphere. To meet this objective, substrate binding and activity assays with electronic mimics of NHase that lack S-oxygenated ligands will be investigated. Further, Ru model complexes that incorporate S-oxygenation will be developed to probe their second coordination sphere effects and new ligands with alternate second coordination sphere moieties will be prepared and evaluated. The second specific aim will probe the NHase oxygen-sensitivity of iron-thiolates. The hypothesis that oxygen sensitivity of Fe-thiolates is spin-state dependent with low-spin Fe yielding S-oxygenates and high-spin Fe forming disulfides and Fe-oxo clusters will be evaluated via reactivity studies on a series of Fe complexes with varying spin-states. Complimentary density functional theory investigations to elucidate the electronic structure effects will be conducted. Additionally, the hypothesis that chelate ring size can enforce S-coordination of Fe S-oxygenates will be evaluated through the design and synthesis of new ligand motifs. The broader impacts of this study focus on promoting teaching, training and learning and broadening the participation of students in an underrepresented region. This project will provide training for post-doctoral fellows and graduate students working alongside undergraduate researchers and high school students in the fields of synthesis, spectroscopy, reactivity, and computation. Undergraduate students will be recruited locally and from regional undergraduate institutions. Additionally, collaborative efforts with a faculty member and students at a primarily undergraduate institution (PUI) are in place. The annual, regional undergraduate research symposium initiated by the PI as a mechanism for students and faculty at PUIs to present research will be continued with the aim of including industrial participation to bridge the gap between industry and undergraduate students. This symposium has been successful at attracting female and underrepresented minorities, including participants from a historically black university.

无机，生物无机和有机化学计划的这一奖项支持路易斯维尔大学克雷格Grapperhaus教授的研究，该研究专注于腈水合酶（NHase）的功能模型复合物和硫醇铁的相关氧敏感性。该项目包括目标复合物的合成和光谱表征，以及反应性研究和计算方法，以了解电子结构和反应性之间的关系。第一个具体的目的是测试的假设，功能性NHase模型模拟S-氧化作用，包括调整刘易斯酸度和底物活化/中间体稳定通过第二个协调领域。为了满足这一目标，将研究缺乏S-含氧配体的NHase电子模拟物的底物结合和活性测定。此外，钌模型配合物，将开发的S-氧化探测其第二个协调领域的影响和新的配体与交替的第二个协调领域的部分将被制备和评估。第二个具体目标将探测硫醇铁的NH酶氧敏感性。通过对一系列具有不同自旋状态的Fe络合物的反应性研究，将评估Fe硫醇盐的氧敏感性与低自旋Fe产生S-含氧化合物和高自旋Fe形成二硫化物和Fe-氧簇的自旋状态相关的假设。将进行补充密度泛函理论研究，以阐明电子结构的影响。此外，假设螯合环的大小可以加强铁S-含氧化合物的S-协调将通过设计和合成新的配体图案进行评估。这项研究的更广泛影响侧重于促进教学、培训和学习，扩大代表性不足区域学生的参与。 该项目将为博士后研究员和研究生提供培训，与本科研究人员和高中生一起在合成，光谱学，反应性和计算领域工作。 本科生将在当地和区域本科院校招募。此外，与教师和学生在一个主要的本科院校（PUI）的协作努力已经到位。由PI发起的年度区域本科生研究研讨会作为PUI学生和教师的研究机制将继续进行，目的是包括工业参与，以弥合工业和本科生之间的差距。这次研讨会成功地吸引了女性和代表性不足的少数群体，包括来自一所历史悠久的黑人大学的与会者。