精确结构的水溶性金/银团簇可控合成、性质及其在生命科学中的应用探索

The precise structure of metal nanoclusters is essential to research the relationship between the accumulation of atoms and properties. In this project, we will synthesize some water-soluble ligands, which are similar to the biomimetic molecules. And then these water-soluble ligands will be used to react with the water-insoluble Au/Ag nanoclusters with defined structure, by the ligand-exchange methods in two-phase system. With the help of various modern analytic technologies and controlled reaction conditions, the water-insoluble ligands will be replaced by parts or all the water-soluble ligands with the same metal core. Thus, a new method to synthesize water-soluble gold/silver nanoclusters with high yields will be established. And these nanoclusters will possess precise structure and good biocompatibility. Based on this, we can research that how the ligands affect the physicochemical properties and the size of metal core of the metal nanoclusters. In combination with theoretical calculation, the interaction mechanism of the gold/silver nanoclusters’ structure and the biological molecules, cell can be studied. And on this basis, the subcellular localization groups can be connected onto the surface of the water-soluble ligands, and new metal nanoclusters with the functions of subcellular localization will be obtained, which can enhance the aggregative ability in organelles for nanoclusters induced by their ultrasmall size. After that, we also can explore the targeting ability of the metal nanoclusters in the cell. This project will hopefully lay the foundation for synthesizing efficient, safe and high-quality Au/Ag nanoclusters in accurate medical field.

精确的结构是研究团簇中原子的堆积方式与性质关系的基础。本项目拟设计合成水溶性仿生物分子配体，将系列具有明确结构的非水溶性金/银团簇，采用两相可控配体交换方法，结合多种现代分析技术跟踪，精确控制配体交换条件，在团簇核保持不变的前提下，使外围配体被水溶性配体部分或全部交换。建立可控高效合成精确结构的水溶性金/银团簇的新方法,合成具有精确结构的生物相容性好的水溶性金/银团簇。研究配体的改变与团簇的物理化学性质、金属核与配体的表/界面性质变化的关系。结合理论计算，探讨金/银团簇的结构与生物分子及在细胞中的作用机理。在此基础上，应用后合成方法将精确结构的水溶性金/银团簇引入亚细胞定位基团，获得亚细胞靶向的水溶性金/银团簇，提高团簇超小尺寸带来的可以在细胞器中聚集的潜力, 研究其在细胞中的靶向作用。为开发面向精准医学的高效、安全、质量可控的金/银团簇奠定基础。

对生物活性物质（离子、信号小分子、蛋白质等）进行实时、原位的检测为了解这些物质在细胞,特别是亚细胞中所执行的生物功能十分必要。由于具有超小的尺寸（<2纳米）、强荧光、优异的光和生物稳定性、以及独特的无机金属核-有机壳结构，金/银团簇有望成为新一代生物成像与检测材料。.本项目中我们建立原位两相配体交换、再生长等结构精确的金属团簇合成新策略，合成系列具有明确结构的非水溶性金/银团簇，解析了100余种金属团簇的晶体结构。构建了从单金属到四金属的M29金属团簇库。通过疏水性团簇的胶束组装与两相配体交换等方法，建立可控高效合成精确结构的水溶性金/银团簇的新方法,合成具有精确结构的生物相容性好的水溶性金/银团簇，实现了功能导向性水溶性金/银团簇的靶向合成。合成短肽ECGaa保护的发光金团簇，应用表面配体的特异性识别自发负载万古霉素。基于精确结构基础上，研究团簇的前线分子轨道与其理化性质之间的量子化学规律，部分阐明了团簇结晶诱导、自由电子内缩等荧光发生机制。通过表面配体的振动/转动受限实现荧光增强，设计合成了系列具有高光量子产率的具有精确结构的金/银团簇。开展了精确结构的金属团簇在生物应用方面的研究探索。结合理论计算，探讨金/银团簇的结构与生物分子的作用机理。将水溶性金属团簇成功应用于细胞成像。通过团簇表面配体修饰实现团簇分子的细胞器靶向成像。构建了基于荧光团簇的多层次组装材料，实现了精确结构团簇在生物体内的多功能高效诊疗。本项目的实施为开发面向精准医学的高效、安全、质量可控的金/银团簇奠定了基础。