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Excellence in Research: Near-Infrared Molecular Probes as Potential Tools for Bioimaging

卓越的研究：近红外分子探针作为生物成像的潜在工具

基本信息

批准号：
2100629
负责人：
Fasil Abebe
金额：
$ 38.11万
依托单位：
Morgan State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-15 至 2024-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2100629&HistoricalAwards=false
关键词：
Excellence Research Near Infrared Molecular

项目摘要

With this award, the Chemical Structure, Dynamics, and Mechanism-B program is supporting Dr. Fasil Abebe at Morgan State University to develop synthetic near-infrared fluorescent probes for rapid visualization and quantification of cellular metal ions. This challenging objective first requires the synthesis of a series of structurally related organic dye molecules that are designed to undergo structural change upon metal ion coordination. The resulting fluorophores (light-emitting structures) are expected enable the imaging of metal ions in live cells by using high-resolution fluorescence microscopy. This project will explore the synthesis, optical and electrochemical properties of these dye molecules. Fluorescent probes have become indispensable tools in modern biology and biotechnology because they provide real time information concerning the quantity of ions or molecules of interest within the living cell. Thus, the probes developed in this project may spur significant advances in our understanding of metal-cell biology. Developing near-infrared fluorescent probes for metal ions that behave well under physiological conditions is highly desirable. The project enriches education and training of graduate and undergraduate students from underrepresented minority groups by involving them in cutting-edge research activities. Students will develop laboratory expertise in microwave-assisted synthesis, spectroscopic analysis, and fluorescence imaging.The central theme of this project is that principles of organic chemistry, microwave-assisted synthesis and knowledge of photochemistry can be exploited to make an array of molecular tools capable of investigating biological metal ions. Efforts will be focused on the development of cyanine-coupled dye derivatives with good water solubility, cell permeability and photostability. This project includes the following aims: (1) to develop an efficient microwave-assisted synthesis and characterization of near-infrared dye molecules; (2) to examine the spectroscopic, computational, and electrochemical properties of cyanine-coupled dye derivatives by diverse methods; and (3) to investigate the potential of cyanine-coupled dye derivatives for imaging of metals in HeLa cells. A series of rhodamine-cyanine-coupled dyes will first be synthesized. In the presence of metals such as copper, near infrared fluorescence of these dyes occurs by a coordination-induced spirocycle-opening reaction and photo-induced electron transfer (CIPET) process. The role of various factors affecting the analytical characteristics of near-infrared probes, their selectivity and sensitivity toward specific metal ions, as well as other important characteristics will be studied. Metal ions of biological and environmental interest such as copper will be studied. An integral part of this project is the use of density functional theory (DFT) and time-dependent DFT to understand the fluorescence change by metal ions and the ability of metal-dye complexes to act as anion sensors. The detailed training program for underrepresented minority students, both undergraduate and graduate, in this area of research is expected to make an important contribution in the development of a diverse workforce for the nation.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.

通过该奖项，化学结构、动力学和机理- b项目将支持摩根州立大学的Fasil Abebe博士开发用于快速可视化和定量细胞金属离子的合成近红外荧光探针。这个具有挑战性的目标首先需要合成一系列结构相关的有机染料分子，这些分子被设计成在金属离子配位时发生结构变化。由此产生的荧光团（发光结构）有望通过高分辨率荧光显微镜对活细胞中的金属离子进行成像。本项目将探索这些染料分子的合成、光学和电化学性质。荧光探针已经成为现代生物学和生物技术中不可或缺的工具，因为它们可以提供有关活细胞内离子或分子数量的实时信息。因此，在这个项目中开发的探针可能会促进我们对金属细胞生物学的理解取得重大进展。开发在生理条件下表现良好的金属离子近红外荧光探针是非常必要的。该项目通过让未被充分代表的少数群体的研究生和本科生参与前沿研究活动，丰富了他们的教育和培训。学生将在微波辅助合成、光谱分析和荧光成像方面发展实验室专业知识。该项目的中心主题是有机化学原理、微波辅助合成和光化学知识可以被利用来制造一系列能够研究生物金属离子的分子工具。今后将重点开发具有良好水溶性、细胞渗透性和光稳定性的菁偶联染料衍生物。本项目包括以下目标：(1)开发一种高效的微波辅助近红外染料分子的合成和表征方法；(2)通过多种方法研究菁偶联染料衍生物的光谱、计算和电化学性质；(3)研究花氨酸偶联染料衍生物在HeLa细胞中金属成像的潜力。首先合成了一系列罗丹明-花青素偶联染料。在铜等金属的存在下，这些染料的近红外荧光通过配位诱导螺旋循环开启反应和光诱导电子转移（CIPET）过程发生。本文将研究各种因素对近红外探针分析特性、对特定金属离子的选择性和灵敏度以及其他重要特性的影响。对铜等具有生物和环境意义的金属离子将进行研究。这个项目的一个组成部分是使用密度泛函理论（DFT）和时间依赖的DFT来理解金属离子的荧光变化和金属染料配合物作为阴离子传感器的能力。在这一研究领域，为未被充分代表的少数民族学生提供详细的培训计划，包括本科生和研究生，预计将为国家多样化劳动力的发展做出重要贡献。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。