LEAPS-MPS:Molecular Design, Synthesis, Properties, and Application of 2,5-bis(2-(4-nitrophenyl)ethynyl)thiophene Photolabile Protecting Groups for the Synthesis of Hydroxamic Acids

LEAPS-MPS：2,5-双(2-(4-硝基苯基)乙炔基)噻吩光不稳定保护基的分子设计、合成、性质及在异羟肟酸合成中的应用

• 批准号: 2137454
• 负责人: Carl Saint-Louis
• 金额: $ 24.96万
• 依托单位: Kennesaw State University Research and Service Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2137454&HistoricalAwards=false
• 关键词: LEAPS; MPS; Molecular; Design; Synthesis

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). In this project, funded by the Mathematical and Physical Sciences Directorate and the Chemistry Division, Professor Carl Saint-Louis and his students at Kennesaw State University (KSU) will study improved methods for synthesizing hydroxamic acids (HAs). HAs are chemicals that are utilized in many potential medical applications, including synthesis of drugs used in the treatment of cancer. In the organic synthesis field, HAs are utilized as precursors for a broad range of carbon-based chemical reactions, and as agents designed to bind to different metals. Synthesis and purification of HAs is challenging. Prof. Saint-Louis’s research will improve the synthesis of HA by eliminating the use of harsh and toxic conditions during the reactions and will facilitate purification of resulting HAs by reducing the by-products formed. Prof. Saint-Louis also plans to broaden participation in chemistry by students underrepresented in STEM fields by developing a strong undergraduate research program in his lab, and by building a mentoring group for underrepresented minority students on the KSU campus. He will not only leverage his own experiences to help support this large group of URM students, but will also bring URM scientists from off campus as speakers and role models. Professor Saint-Louis proposes to develop 2,5-bis(2-(4-nitrophenyl)ethynyl)thiophene (BNPET) photolabile protective groups (PPGs) with a diagnostic fluorescent by-product that would be utilized to quantify the amount of hydroxamic acid (HA) product formed. It has been shown that a major limitation of most o-nitrobenzyl (o-NB) PPGs derivatives is that their chromophores absorb light mostly in the UV region of the spectrum where extended exposure of cells or tissues to UV light can lead to cell damage or death. Proposed work will pave the way for the synthesis of various conjugated PPGs that absorb in the visible region of the spectrum for efficiency in biological applications. Prof. Saint-Louis will work to provide an improved understanding of the electronic properties of conjugated o-NB PPGs. Results from the planned work will have broad scientific impact by facilitating development of a new method to synthesize highly functional biologically relevant HA via a photo-cleavable protecting group. Work will be performed primarily by undergraduate students, and Prof. Saint-Louis will involve a large number of URM students directly in the planned research, in addition to serving as a mentor and role model to URM students campus-wide.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.

该奖项是根据2021年《美国救援计划法》（公法117-2）全部或部分资助的。在这个项目中，由数学和物理科学局和化学部门资助，卡尔·圣路易斯教授及其在肯尼索州立大学（KSU）的学生将研究合成羟氨基酸的改进方法（HAS）。具有在许多潜在的医疗应用中使用的化学物质，包括合成用于治疗癌症的药物。在有机合成场中，已用作广泛的基于碳的化学反应的前体，并用作旨在与不同金属结合的试剂。综合和纯化的质疑是挑战的。圣路易斯教授的研究将通过消除反应期间的HARMH和有毒条件的使用来改善HAS的综合，并通过减少形成的副产品来促进产生的纯化。圣路易斯教授还计划通过在他的实验室中制定一项强大的本科研究计划，并为KSU校园内代表性不足的少数族裔学生建立一个心理小组，从而扩大了在STEM领域中人数不足的学生参与化学的参与。他不仅将利用自己的经验来帮助支持这群大批URM学生，而且还将将URM科学家带入校园外的演讲者和榜样。圣路易斯教授提出的提议开发了2,5-双（2-（4-硝基苯）乙基）噻吩（BNPET）光值保护基团（PPGS），并具有诊断荧光副产物，可用于量化形成的羟氨酸（HA）产物的量。已经表明，大多数O-硝基苯基（O-NB）PPGS衍生物的主要局限性是它们的发色团主要吸收光谱中的光，主要是在频谱的紫外线区域中吸收光，在该区域中，细胞或组织向UV光的扩展暴露会导致细胞损伤或死亡。拟议的工作将为合成各种共轭的PPG铺平道路，这些PPG在频谱的可见区域中吸收的生物应用效率。 Saint-Louis教授将努力提高人们对共轭O-NB PPG的电子特性的了解。计划中的工作的结果将通过支持开发一种新方法，通过可通过照片可转换的保护组来综合高度功能相关的HA，从而产生广泛的科学影响。工作将主要由本科生进行，圣路易斯教授将直接参与计划的研究，除了作为范围内URM学生校园的心理和榜样外，这一奖项反映了NSF的法定任务，并认为通过基金会的知识优点和广泛的crietia进行评估，并被认为是值得通过评估来支持的。