CAREER: Understanding the Role of Nickel-Sulfur Complexes in Catalytic ROS Detoxification: Insight From Ni-SOD Synthetic Analogues

职业：了解镍硫复合物在催化 ROS 解毒中的作用：来自 Ni-SOD 合成类似物的见解

• 批准号: 0953102
• 负责人: Todd Harrop
• 金额: $ 62.68万
• 依托单位: University of Georgia Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0953102&HistoricalAwards=false
• 关键词: CAREER; Understanding; Role; Nickel; Sulfur

The Chemical Catalysis Program supports Professor Todd C. Harrop at the University of Georgia for a research project that will advance our understanding of the chemistry of biologically relevant metal-sulfur coordination units in their catalytic role as scavengers of reactive oxygen species (ROS) in metalloenzymes. Current knowledge in this area stipulates that such coordination units should be prone to ligand-based oxidation instead of primarily metal-centered redox. Thus, to understand the fundamental chemical properties of these systems, Professor Harrop will initiate a synthetic bioinorganic-modeling approach towards the newest and most unusual superoxide-detoxifying enzyme namely, nickel superoxide dismutase (Ni-SOD). To address the role of biological coordination, the PI will synthesize and characterize a range of Ni-N/S complexes that are direct electronic and structural mimics of Ni-SOD. The fundamental reaction chemistry of Ni with ROS, in particular Ni-S and Ni(III) complexes, is poorly defined and relatively unexplored. Thus, the reactions of these complexes with ROS like superoxide, H2O2, and NO will be performed. These reactivity studies will be monitored by a variety of spectroscopic and computational methods that will define discreetly for the first time these biologically important interactions. Collectively, the contribution of these studies will allow the understanding of new concepts in the unique coordination and reaction chemistry of Ni-SOD and result in the intelligent design of molecules with SOD activity for use in catalysis and pharmaceuticals, thus contributing to a significant stream of research.With the support of the Chemical Catalysis Program in the Chemistry Division at the National Science Foundation, Dr. Harrop will provide biochemists and theoreticians with spectroscopic, structural, and reactive benchmarks of potential species that are important to understanding the Ni-SOD catalytic pathway. This work will also have a broader impact on science education through a variety of synergistic activities. The principal goal of these integrated educational activities is to increase awareness, participation, and retention of underrepresented minority groups in the STEM disciplines, specifically African-Americans in chemistry. These efforts involve a new research-partnership initiative that the PI will establish with Fort Valley State University (FVSU), a public HBCU in the state of Georgia. A summer research internship will be awarded annually throughout the grant period to an undergraduate chemistry major from FVSU to be conducted in the PI's lab on Ni-SOD analogues. The award will establish a new link with an HBCU in the state and will lead to a strong and continual pipeline of FVSU students pursuing advance degrees in chemistry and hopefully at UGA. This award will support salary for the undergraduate summer researcher and for their travel to conferences, better preparing these young scientists for careers in chemical research.

化学催化项目支持乔治亚大学的Todd C. Harrop教授的一项研究项目，该项目将促进我们对金属酶中与生物相关的金属-硫配位单元的化学作用的理解，因为它们是活性氧（ROS）的清除剂。目前在这一领域的知识规定，这种配位单元应该倾向于基于配体的氧化，而不是主要以金属为中心的氧化还原。因此，为了了解这些系统的基本化学性质，Harrop教授将对最新和最不寻常的超氧化物解毒酶即镍超氧化物歧化酶（Ni-SOD）发起合成生物无机建模方法。为了解决生物配位的作用，PI将合成和表征一系列Ni-N/S复合物，这些复合物是Ni-SOD的直接电子和结构模拟物。Ni与ROS的基本反应化学，特别是Ni- s和Ni（III）配合物，定义不清，相对未被探索。因此，这些配合物将与ROS如超氧化物、H2O2和NO发生反应。这些反应性研究将通过各种光谱和计算方法进行监测，这些方法将首次谨慎地定义这些生物学上重要的相互作用。总的来说，这些研究的贡献将使人们能够理解Ni-SOD独特的配位和反应化学中的新概念，并导致具有SOD活性的分子的智能设计，用于催化和药物，从而促进重要的研究流。在美国国家科学基金会化学部化学催化项目的支持下，Harrop博士将为生物化学家和理论家提供对理解Ni-SOD催化途径非常重要的潜在物种的光谱、结构和反应基准。这项工作还将通过各种协同活动对科学教育产生更广泛的影响。这些综合教育活动的主要目标是提高STEM学科中代表性不足的少数群体的认识、参与和保留，特别是化学领域的非裔美国人。这些努力包括PI将与乔治亚州的公立HBCU Fort Valley州立大学（FVSU）建立一项新的研究伙伴关系倡议。在整个资助期间，每年将为FVSU化学专业的本科生提供一个暑期研究实习机会，在PI的实验室进行Ni-SOD类似物的研究。该奖项将与该州的HBCU建立新的联系，并将为FVSU学生提供强大而持续的管道，以攻读化学高级学位，并希望进入佐治亚大学。该奖项将支持本科暑期研究员的工资和参加会议的旅费，为这些年轻科学家从事化学研究做好更好的准备。