EuroTracker Dyes: Synthesis and Application in Functional Cell Imaging

EuroTracker 染料：合成及其在功能细胞成像中的应用

• 批准号: EP/L019124/1
• 负责人: David Parker
• 金额: $ 45.59万
• 依托单位: Durham University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FL019124%2F1
• 关键词: EuroTracker; Dyes; Synthesis; Application; Functional

The visualisation of certain living cells or microbes by optical microscopy requires the introduction of bright, luminescent dyes or stains, that can light up selected parts of the cell effectively.We will develop bright complexes of the rare earth element, europium, (EuroTracker dyes) as optical probes that emit light efficiently and report information back to the observer about their chemical or biological environment. These probes have been designed to allow them to be excited by the light sources that are available in microscopes used by physical scientists, biochemists and cell biologists, to study the interior composition of cells or related small compartments. By examining series of closely related probes, we shall define systems that locate to a particular compartment of a cell, allowing it to be visualised selectively. The optical probes that are currently used are based either on organic compounds, on large man-made proteins or on so-called quantum dots; each of these probes suffer from problems of low chemical stability, a tendency to fade and, in certain cases, they are rather toxic to the living cell. Thus we aim to change the thinking of the microscopy community and to pave the way for such emissive metal complexes to be used as stains and probes in biology. These metal complex probes emit light over longer timescales than conventional probes, and so their is more time to collect the emitted light after pulsed excitation and only short exposure times to the light that is used to excite them. The long emission lifetime avoids problems in data acquisition that are associated with light scattering and background autofluorescence. In parallel, we shall develop instrumentation methods that allow the spectral signature of these probes to be recorded quickly using fast imaging methods. We shall work with microscope manufacturers and with optics specialists to this end. This will allow changes in chemical composition within a cell to be tracked on a 10 second timescale. As a first step, we shall develop probes that can report on pH change and on the amount of sodium, magnesium and zinc within a specific cell compartment, allowing changes in the amount of these important metal ions to be tracked in living cells in real time. By adopting a modular approach to probe design, different metal ions can be examined subsequently, by introducing the appropriate metal-binding moiety into the probe structure.

通过光学显微镜观察某些活细胞或微生物需要引入明亮的发光染料或染色剂，它们可以有效地照亮细胞的选定部分。我们将开发稀土元素铕的明亮复合物（EuroTracker 染料）作为光学探针，可以有效地发光并向观察者报告有关其化学或生物环境的信息。这些探针的设计目的是让它们能够被物理科学家、生物化学家和细胞生物学家使用的显微镜​​中的光源激发，以研究细胞或相关小隔室的内部组成。通过检查一系列密切相关的探针，我们将定义定位到细胞特定区室的系统，从而使其能够选择性地可视化。目前使用的光学探针基于有机化合物、大型人造蛋白质或所谓的量子点；这些探针中的每一种都存在化学稳定性低、容易褪色的问题，并且在某些情况下，它们对活细胞具有相当大的毒性。因此，我们的目标是改变显微镜界的思维，并为此类发射金属配合物用作生物学染色剂和探针铺平道路。这些金属络合物探针比传统探针在更长的时间范围内发光，因此它们在脉冲激发后有更多时间收集发射的光，并且对用于激发它们的光的曝光时间较短。较长的发射寿命避免了与光散射和背景自发荧光相关的数据采集问题。与此同时，我们将开发仪器方法，允许使用快速成像方法快速记录这些探针的光谱特征。为此，我们将与显微镜制造商和光学专家合作。这将允许在 10 秒的时间尺度内跟踪细胞内化学成分的变化。第一步，我们将开发能够报告特定细胞室中 pH 变化以及钠、镁和锌含量的探针，从而能够实时跟踪活细胞中这些重要金属离子含量的变化。通过采用模块化方法进行探针设计，通过将适当的金属结合部分引入探针结构中，可以随后检查不同的金属离子。

项目成果

Synthesis, stereocontrol and structural studies of highly luminescent chiral tris-amidepyridyl-triazacyclononane lanthanide complexes.

高发光手性三酰胺吡啶基三氮杂环壬烷镧系配合物的合成、立体控制和结构研究。

• DOI: http://dx.10.1039/c3dt53000k
• 发表时间: 2014
• 期刊: 2003)
• 作者: Neil ER

Selective ion pair recognition of citrate and zinc ions in water by ratiometric luminescence signaling

通过比率发光信号选择性离子对识别水中柠檬酸根和锌离子

• DOI: http://dx.10.1039/c4ra07894b
• 发表时间: 2014
• 期刊: RSC Adv.
• 作者: McMahon B

Very bright, enantiopure europium(iii) complexes allow time-gated chiral contrast imaging.

非常明亮的对映体纯铕(iii)络合物可实现时间选通手性对比成像。

• DOI: http://dx.10.1039/c6cc07313a
• 发表时间: 2016
• 期刊: Chemical communications (Cambridge, England)
• 作者: Frawley AT

Enantioselective cellular localisation of europium(iii) coordination complexes.

铕(iii)配位络合物的对映选择性细胞定位。

• DOI: http://dx.10.1039/c7sc04422d
• 发表时间: 2018
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Frawley AT

Bright, highly water-soluble triazacyclononane europium complexes to detect ligand binding with time-resolved FRET microscopy.

明亮、高度水溶性的三氮杂环壬烷铕络合物，可通过时间分辨 FRET 显微镜检测配体结合。

• DOI: 10.1002/anie.201406632
• 发表时间: 2014-09-26
• 期刊: Angewandte Chemie
• 作者: M. Delbianco;V. Sadovnikova;Emmanuel Bourrier;G. Mathis;L. Lamarque;J. Zwier;D. Parker
• 通讯作者: D. Parker