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

具体目标：在对双视反式苯基乙烯基-bipy框架进行初步研究的基础上，本小组将寻求(1)将高灵敏度和选择性的锌配位基序纳入反式苯基乙烯基-bipy框架中，以提供灵敏度和有效浓度范围均适合生理成像的锌选择性双视荧光探针；(2)建立在缺乏锌的情况下实现反式芳基乙烯基双位配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自由形式和锌结合形式之间产生大的荧光对比至关重要；(3)进一步开发对锌具有高灵敏度和选择性的含三唑基四detate配体，适合双位配体设计；(4)研制高灵敏度、大有效浓度范围、激发波长长、发射波长深可见区的锌探针，防止活体生物样品的自身荧光和光损伤。智力优势：(1)异位氟离子体系解决了一个极具挑战性的科学问题，即开发在整个6个数量级生理浓度范围内有效的锌离子荧光探针。该项目的成功将提供锌离子荧光探针，能够在大浓度范围内定量分析生物化学过程中的锌通量。这些信息对于阐明锌的生理作用是必不可少的，反过来，将有助于诊断和治疗包括阿尔茨海默病在内的锌体内平衡明显破坏的疾病。(2)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，这在基础层面上具有重要意义。综上所述，该应用的成功不仅填补了活细胞成像技术发展的空白，而活细胞成像技术的目标是生理上重要的锌，锌的浓度在细胞活动中可能在很大范围内变化，而且还促进了对锌配位化学和配位驱动光物理过程的理解。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光物理过程的基本理解，开发针对信号转导和代谢途径中生理浓度范围较大的物质的传感技术。本文提出的扩大锌离子分析浓度范围的原理可应用于中性和阴离子。(2)在此应用中研究的配位化学和光物理过程有望影响其他领域的技术发展，如分子逻辑学和分子电子学。(3)参与该项目的各类学生将接受包括合成化学、协调化学和分析化学在内的跨学科培训。

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.