Oxygen Sensitivity and Functional Models of Nitrile Hydratase

这个无机、生物无机和有机金属化学项目的奖项支持路易斯维尔大学的Craig Grapperhaus教授的研究，他的研究重点是腈水合酶（NHase）的功能模型复合物和硫代酸铁的相关氧敏感性。该项目包括目标配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。第一个具体目标是验证功能性nase模型模拟s -氧合效应的假设，包括通过第二个配位球调节Lewis酸度和底物活化/中间体稳定。为了实现这一目标，将研究缺乏s氧配体的nase电子模拟物的底物结合和活性测定。此外，还将开发含s -氧合的Ru模型配合物，以探索其第二配位球效应，并制备和评价具有替代第二配位球基团的新配体。第二个具体目标是探索铁硫酸盐的nase氧敏感性。硫代铁的氧敏感性与低自旋产铁的s -氧合物、高自旋形成铁的二硫化物和铁-氧簇的自旋态相关的假设将通过一系列不同自旋态的铁配合物的反应性研究来评估。互补密度泛函理论研究将阐明电子结构效应。此外，通过设计和合成新的配体基序来评估螯合环大小可以增强铁s氧合物的s配位的假设。这项研究的更广泛影响集中在促进教学、培训和学习，并扩大代表性不足地区学生的参与。该项目将为在合成、光谱学、反应性和计算领域与本科生和高中生一起工作的博士后研究员和研究生提供培训。本科生将从本地和地方本科院校招收。此外，与主要本科机构（PUI）的教师和学生的合作努力已经到位。由学院发起的每年一次的地区性本科生研究研讨会，将继续为大学师生提供一个展示研究成果的机制，目的是让产业界参与进来，弥合产业界与本科生之间的差距。这次研讨会成功地吸引了女性和代表性不足的少数民族，包括来自一所历史悠久的黑人大学的参与者。

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.