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

该奖项的全部或部分资金来自《2021年美国救援计划法案》(公法117-2)。在这个由数学和物理科学委员会和化学系资助的项目中，Kennesaw State University(KSU)的Carl Saint-Louis教授和他的学生将研究合成异羟肟酸(HAS)的改进方法。HAS是用于许多潜在医疗应用的化学物质，包括用于治疗癌症的药物的合成。在有机合成领域，HAS被用作广泛的碳基化学反应的前体，以及用作与不同金属结合的试剂。HAS的合成和纯化具有挑战性。圣路易斯教授的研究将通过避免在反应过程中使用苛刻和有毒的条件来改进HA的合成，并将通过减少副产物的形成来促进所产生的HA的提纯。圣路易斯教授还计划通过在他的实验室开发一个强大的本科生研究项目，并在科罗拉多州立大学校园为未被充分代表的少数族裔学生建立一个辅导小组，来扩大STEM领域代表性不足的学生对化学的参与。他不仅将利用自己的经验来帮助支持这一大群URM学生，而且还将邀请来自校外的URM科学家作为演讲者和榜样。圣路易斯教授建议开发2，5-双(2-(4-硝基苯基)乙炔)噻吩基(BNPET)耐光保护基团(PPG)，该保护基团具有诊断荧光副产物，将用于定量生成异羟肟酸(HA)产物的数量。研究表明，大多数邻硝基苯基(o-NB)PPG衍生物的主要局限性是它们的生色团主要吸收光谱的紫外区的光，在那里细胞或组织长时间暴露在紫外光下会导致细胞损伤或死亡。拟议的工作将为合成各种吸收可见光谱的共轭PPG铺平道路，从而提高生物应用的效率。圣路易斯教授将致力于更好地理解o-Nb共轭PPG的电子性质。计划工作的结果将产生广泛的科学影响，促进开发一种新的方法，通过光可裂解保护基团合成高度功能的生物相关HA。工作将主要由本科生完成，圣路易斯教授将直接让大量URM学生参与计划中的研究，此外还将在全校范围内充当URM学生的导师和榜样。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.