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

职业：几何和电子对血红素超氧化物中间体的仿生反应活性的贡献

• 批准号: 2422277
• 负责人: Gayan Wijeratne
• 金额: $ 71万
• 依托单位: University of Alabama Tuscaloosa
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-04-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2422277&HistoricalAwards=false
• 关键词: CAREER; Geometric; Electronic; Contributions; Bio

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.

在化学过程的化学过程中，化学过程和启发竞争性研究的既定计划（EPSCOR）的支持（EPSCOR）伯明翰阿拉巴马大学的Gayan B. Wijeratne博士将调查小分子的化学与血红素铁心中心的化学，例如在人类生物学中促进氧气的化学。这些模型系统可能是非常通用的，但可以直接探测，以理解控制生物学中氧介导的反应性的复杂机理细节。 Wijeratne博士和他的团队将利用这些强大的工具来阐明但未知的知识，这可能会导致有效合成复杂分子的途径，并发现催化剂可以提高氧气减少氧化能量的效率，从而促进替代能源的替代能源应用。这项工作将涉及以生物启发的设计和合成新鲜模型系统的合成，这些模型系统结合了有机和无机合成工具包，以及对生物功能的相似之处的反应性的分析。同样，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。该项目的外展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将其定向。拟议的努力将努力弥合伯明翰市年轻人的科学素养差距，伯明翰市是该国收入最多的学区之一。 含血红素的双氧酶在人类生理学，疾病进展和衰老中起关键作用，因此在过去十年中吸引了实质性的研究兴趣。但是，有关这些的确切机制细节只有微弱的理解。假定血红素超氧化物加合物是血红素双加氧酶中的活性氧化剂，但是，与其在实际酶机制中的确切参与有关的细节仍然难以捉摸。合成模型系统长期以来一直是解决此类机械歧义的强大工具，但是通常发现合成血红素超氧化物加合物是缓慢的氧化剂。这种异常要求对合成系统的显式建模进行重估，并与其生物学作用方式直接相关。理解此类模型系统的机理细节也可以直接有益于设计针对重要的复杂有机分子和均质二氧化催化剂的优质合成方法，用于替代能源应用。拟议的研究将通过产生具有不同结构特性的合成血红素超氧化物模型系统的库来解决知识的差距，并彻底研究这种结构调制将如何影响其反应性特征。这项工作将垂直提高对反应性的几何，电子和非共价结构特性的基本理解，中期血红素氧中间体，引入了血红素氧模型化学的新时代。该项目的宣传活动将通过尖端的研究机会和高质量的一对一指导机会直接受益于大多数代表性的高中生，旨在加强其在区域科学博览会上的准备阶段，这一奖项反映了NSF的法定任务，并通过评估了基金会的范围，并反映了NSF的法定任务。