Heteroditopic Fluoroionophores for Zinc Ion - Coordination Chemistry, Photophysics, and Sensing Applications

用于锌离子的异二位氟离子载体 - 配位化学、光物理学和传感应用

• 批准号: 0809201
• 负责人: Lei Zhu
• 金额: $ 33万
• 依托单位: Florida State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2012-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0809201&HistoricalAwards=false
• 关键词: Heteroditopic; Fluoroionophores; Zinc; Ion; Coordination

Specific Objectives: Based on preliminary studies on the ditopic trans-phenylvinyl-bipy framework, the group will seek to (1) incorporate highly sensitive and selective zinc-coordination motifs into the trans-phenylvinyl-bipy framework to afford zinc-selective ditopic fluorescent probes with both sensitivity and effective concentration range suitable for physiological imaging; (2) establish general principles for achieving highly efficient intramolecular photoinduced electron transfer (PET) of trans-arylvinylbipy-based ditopic ligands in the absence of zinc, which is critical in creating large fluorescence contrast between free and zinc-bound forms of the probe molecules; (3) further develop triazolyl-containing tetradetate ligands with high sensitivity and selectivity to zinc that are amenable to ditopic ligand design; (4) develop zinc probes with both high sensitivity and large effective concentration ranges with long excitation and emission wavelengths deep in the visible region to prevent autofluorescence and photodamage of live biological samples. Intellectual Merit: (1) The heteroditopic fluoroionophoric system provides a solution to a highly challenging scientific problem, which is the development of fluorescent probes for zinc ion that are effective over its entire 6 orders of magnitude physiological concentration range. The success of the proposed project will provide fluorescent probes for zinc ion capable of quantitative profiling of zinc flux in biochemical processes over large concentration ranges. Such information is indispensable to the elucidation of the physiological roles of zinc, and, in turn, will help in the diagnosis and cure of diseases including Alzheimer's where disruption of zinc homeostasis is evident. (2) The designed molecules provide an excellent platform for studying the impact of metal ion coordination on the excited states of organic molecules, which is important on a fundamental level. In summary, the success of this application will not only fill the gap in the development of live cell imaging technologies targeting the physiologically important zinc whose concentrations may vary over enormous ranges during cellular events, but also advance understanding of zinc coordination chemistry and coordination-driven photophysical processes. Broader Impact: (1) The long-term objective of the PI's research program is the development of sensing technologies targeting substances of large physiological concentration ranges in signal transduction and metabolic pathways based upon fundamental understanding of coordination-driven photophysical processes. The principle of extending the analytical concentration range proposed herein for zinc ion can be applied to neutral and anionic species. (2) The coordination chemistry and photophysical processes studied in this application are expected to impact the development of technologies in other areas such as molecular logics and molecular electronics. (3) The diverse range of students participating in this project will receive interdisciplinary training encompassing synthetic, coordination, and analytical chemistry.

具体目标：基于对反式苯乙烯基-bipy结构的初步研究，本课题组将寻求（1）将高灵敏度和选择性的锌配位基序引入反式苯乙烯基-bipy结构中，以提供具有灵敏度和适用于生理成像的有效浓度范围的锌选择性双位荧光探针;（2）建立用于在不存在锌的情况下实现反式-芳基乙烯基bipy基双配位体的高效分子内光诱导电子转移（PET）的一般原理，这对于在探针分子的游离形式和锌结合形式之间产生大的荧光对比度是关键的;（3）进一步开发对锌具有高灵敏度和选择性的含三唑基的十四酸酯配体，其适合于双位配体设计;（四）开发具有高灵敏度和大有效浓度范围的锌探针，具有深可见光区的长激发和发射波长，以防止活体生物的自发荧光和光损伤样品 智力优势：（1）异位荧光离子体系统为高度挑战性的科学问题提供了解决方案，该科学问题是开发在其整个6个数量级生理浓度范围内有效的锌离子荧光探针。该项目的成功将为锌离子提供荧光探针，能够在大浓度范围内定量分析生化过程中的锌通量。这些信息对于阐明锌的生理作用是不可或缺的，并且反过来将有助于诊断和治疗包括阿尔茨海默氏症在内的疾病，其中锌稳态的破坏是明显的。(2)所设计的分子为研究金属离子配位对有机分子激发态的影响提供了一个很好的平台，这在基础水平上是重要的。总之，该应用的成功将不仅填补针对生理上重要的锌（其浓度在细胞事件期间可能在巨大范围内变化）的活细胞成像技术的开发中的差距，而且还促进对锌配位化学和配位驱动的生物物理过程的理解。 更广泛的影响：（1）PI研究计划的长期目标是基于对协调驱动的生物物理过程的基本理解，开发针对信号转导和代谢途径中大生理浓度范围物质的传感技术。本文提出的锌离子分析浓度范围的扩展原则可适用于中性和阴离子物质。(2)该应用中研究的配位化学和电子物理过程预计将影响其他领域的技术发展，如分子逻辑和分子电子学。(3)参与该项目的学生将接受跨学科的培训，包括合成，配位和分析化学。