基于钌-稀土异多核配合物的近红外荧光探针构建及生物成像中应用研究

Lanthanide near-infrared luminescent probes have important application prospects due to their unique luminescence properties in the field of biological fluorescence imaging. The excitation wavelength of near-infrared emitting from lanthanide ions sensitized by organic ligand locates mainly in the near ultraviolet region which limits its application in biomedical field. Therefore the design and synthesis of a series of novel near-infrared luminescent probes using visible light to excite transition metal chromophores to generate sensitized luminescence from near-infrared emitting lanthanide(III) centres and being suited to use in the field of biological fluorescence imaging will become the focus of research in this field. In this project, we will construct a series of new ruthenium-lanthanide heteropolynuclear complexes using the pyridine ligands as the bridging ligands and modifying the auxiliary ligands with the targeting group. Near-infrared luminescence properties of these complexes will be studied under different conditions, to screen out some complexes with preferable optical property for cell and animal imaging studies. The relationship between the structure and properties will be clarified, and the interaction mechanism will be further discussed. The implementation of the project will provide a new strategy and theoretical basis for the research and applications of lanthanide near infrared luminescent probes in the field of biological imaging.

稀土近红外发光探针因具有特殊的荧光性质在生物荧光成像领域具有重要的应用前景。因有机配体敏化稀土离子近红外发光的激发波长主要位于近紫外区而限制其在生物医学领域的应用。因此设计合成采用可见光激发过渡金属发色团来敏化稀土近红外发光且适用于生物荧光成像的新型近红外荧光探针分子将成为这一领域的研究热点。本项目拟以多吡啶配体为桥联配体，在辅助配体上引入靶向基团，构筑一系列新型钌-稀土异多核金属配合物。评价配合物在不同条件下的近红外发光性能，从中筛选出发光性能优异的配合物将其应用于细胞和动物荧光成像研究，阐明其结构与性质的关系，并深入探讨作用机理。本项目的实施将为稀土近红外发光探针在生物成像领域的研究和应用提供新的设计思路和理论依据。

金属配合物荧光探针应用于生物成像中的诊断和治疗的应用是目前小分子化合物生物活性研究的热点和焦点之一。本项目依据项目书的内容合成了多个含单核、异核及多核的金属配合物的荧光探针，分别研究了其在生物成像中诊断和治疗的应用。主要取得以下成果：（1）构建了基于单核、异核金属配合物的近红外发光探针，应用于对细胞中的线粒体形态变化的动态和实时荧光检测。（2）发展了含苯并呋喃环结构的钌配合物荧光染料，成功应用于细胞中线粒体成像。（3）发展了一系列双核钌配合物，具有对特殊序列选择性DNA结构探针及其抑制端粒酶活性。（4）构建了能特异性识别铜离子、汞离子荧光探针，成功应用于细胞线粒中铜离子、汞离子的识别。（5）发展了单核、双核及异核配合物，应用于大肠杆菌、金黄色葡萄球菌及烟曲霉的细菌染色及抗菌活性。（6）设计合成了能靶向富集肿瘤细胞的内质网、线粒体的金属配合物，对肿瘤细胞进行实时检测及抗肿瘤活性。发表了SCI论文6篇，申请专利一项。