CAREER: Geometric and Electronic Contributions to Bio-inspired Reactivities of Heme-superoxide Intermediates

在化学部生命过程计划的化学和刺激竞争性研究（EPSCoR）的既定计划的支持下，Gayan B博士。位于伯明翰的亚拉巴马大学的Wijeratne将研究具有血红素铁中心的小分子的化学性质，例如在人类生物学中激活氧气的小分子。这些模型系统可以是非常通用的，但简单的探针理解复杂的机械细节，管理氧介导的生物反应。Wijeratne博士和他的团队将利用这些强大的工具来揭示未知的知识，这些知识可以导致复杂分子的有效合成途径，以及发现可以提高氧还原催化剂效率的催化剂，从而使替代能源应用受益。这项工作将涉及生物启发的设计和合成的新模型系统，结合联合收割机有机和无机合成工具包，并分析反应性，绘制平行的生物功能。此外，将采用各种低温光谱工具，为高中，本科，研究生和博士后研究人员提供独特的专业技能。该项目的推广和教育方面将涉及伯明翰市高中学生通过新设计的科学俱乐部计划对区域科学博览会的定位。拟议的努力将努力弥合伯明翰市青少年科学素养的差距，伯明翰市是该国收入隔离最严重的学区之一。 含血红素的双加氧酶在人类生理、疾病进展和衰老中起着关键作用，因此在过去十年中吸引了大量的研究兴趣。然而，关于这些的确切的机械细节只是模糊的理解。血红素超氧化物加合物被认为是血红素双加氧酶中的活性氧化剂，然而，关于它们在实际酶促机制中的决定性参与的细节仍然难以捉摸。合成模型系统长期以来一直是解决这种机制模糊性的有力工具，但合成血红素超氧化物加合物往往被发现是缓慢的氧化剂。这种异常要求重新评估合成系统的显式建模与其生物作用模式直接相关。这种模型系统的机械细节的理解也可以是直接有益的上级合成方法的设计，目标是重要的复杂的有机分子和均相分子氧还原催化剂，用于替代能源的应用。拟议的研究将通过生成具有不同结构特性的合成血红素超氧化物模型系统库来解决这一知识缺口，并深入研究此类结构调制如何影响其反应性特征。这项工作将垂直推进的反应性控制几何，电子和非共价结构性质的中间价血红素氧中间体的基本理解，引入血红素氧模型化学的新时代。该项目的推广活动将直接使伯明翰大多数代表性不足的高中生受益，亚拉巴马地区通过尖端的研究机会和高质量的一对一该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响进行评估来支持审查标准。

With support from the Chemistry of Life Processes Program in the Division of Chemistry and the Established Program to Stimulate Competitive Research (EPSCoR) Dr. Gayan B. Wijeratne at the University of Alabama at Birmingham will investigate the chemistry of small molecules with heme iron centers such as the ones that activate oxygen in human biology. These model systems can be extremely versatile, yet straightforward probes for comprehending the complicated mechanistic details that govern oxygen mediated reactivities in biology. Dr. Wijeratne and his team will utilize these powerful tools in shedding light on yet unknown knowledge that can lead to pathways for efficient syntheses of complex molecules, and the discovery of catalysts that can enhance the efficiency of catalysts of oxygen reduction benefiting alternative energy applications. This work will involve bio-inspired design and synthesis of fresh model systems that combine organic and inorganic synthetic toolkits, and analyses of reactivities that draw parallels to biological functionalities. As well, a broad variety of cryogenic spectroscopic tools will be employed, offering a uniquely specialized skillset to contributing high-school, undergraduate, graduate, and postdoctoral researchers. Outreach and educational aspects of this project will involve the orientation of Birmingham City high school students toward Regional Science Fair via a newly designed Science Club program. Proposed efforts will strive to bridge the gap of scientific literacy of youngsters in the City of Birmingham, which is one of the most income-segregated school districts in the country. Heme-containing dioxygenases play pivotal roles in human physiology, disease progression, and aging, consequently attracting substantial research interests within the past decade. However, exact mechanistic details concerning these are only faintly understood. Heme superoxide adducts are presumed to be active oxidants in heme dioxygenases, however, details pertaining to their definitive involvement in the actual enzymatic mechanism remain elusive. Synthetic model systems have long-served as powerful tools in addressing such mechanistic ambiguities, but synthetic heme superoxide adducts are often found to be sluggish oxidants. This anomaly calls for revaluation of explicit modeling of synthetic systems with direct relevance to their biological mode of action. Comprehension of mechanistic details of such model systems can also be of direct benefit for the design of superior synthetic methodologies targeting important complex organic molecules and homogeneous dioxygen reduction catalysts to be used in alternative energy applications. Proposed research will address this gap in knowledge by generating a library of synthetic heme superoxide model systems with divergent structural properties, and thorough investigation into how such structural modulations would influence their reactivity signatures. This work will vertically advance the fundamental understanding of reactivity-governing geometric, electronic, and non-covalent structural properties of mid-valent heme-oxygen intermediates, introducing a new era of heme-oxygen model chemistry. Outreach activities of this project will directly benefit the majority of underrepresented high schoolers in the Birmingham, Alabama area through cutting-edge research opportunities and high-quality one-on-one mentoring opportunities geared toward strengthening their preparatory phase for Regional Science Fair.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.