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.

该奖项全部或部分根据2021年美国救援计划法案（公法117-2）资助。 在这个由数学和物理科学理事会和化学部资助的项目中，肯尼索州立大学（KSU）的卡尔·圣路易教授和他的学生将研究合成异羟肟酸（HA）的改进方法。 HA是用于许多潜在医学应用的化学品，包括用于治疗癌症的药物的合成。 在有机合成领域，HA被用作广泛的碳基化学反应的前体，并被设计为结合不同金属的试剂。 HA的合成和纯化具有挑战性。 Saint-Louis教授的研究将通过消除反应过程中苛刻和有毒条件的使用来改善HA的合成，并通过减少形成的副产物来促进所得HA的纯化。 圣路易斯还计划通过在他的实验室开发一个强大的本科研究项目，并通过在KSU校园内为代表性不足的少数民族学生建立一个辅导小组，来扩大STEM领域学生对化学的参与。 他不仅将利用自己的经验来帮助支持这一大群URM学生，而且还将把URM科学家从校外作为演讲者和榜样。Saint-Louis教授提出开发2，5-双（2-（4-硝基苯基）乙炔基）噻吩（BNPET）光不稳定保护基团（PPG），其具有诊断荧光副产物，可用于定量形成的异羟肟酸（HA）产物的量。 已经表明，大多数邻硝基苄基（o-NB）PPG衍生物的主要限制是它们的发色团主要吸收光谱的UV区域中的光，其中细胞或组织延长暴露于UV光可导致细胞损伤或死亡。 拟议的工作将为合成各种共轭PPG铺平道路，这些PPG在光谱的可见光区域吸收，以提高生物应用的效率。 Saint-Louis教授将致力于提供对共轭o-NB PPG电子特性的更好理解。 计划工作的结果将通过促进开发一种新方法来通过光可裂解的保护基团合成高功能生物相关HA，从而产生广泛的科学影响。 工作将主要由本科生完成，Saint-Louis教授将让大量URM学生直接参与计划中的研究，此外还将担任URM学生的导师和榜样。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审查标准进行评估来支持。