无机/有机杂化强双光子吸收材料的制备、构效关系及生物学应用探索

It is a key problem to study the relationships between the structures and properties for specific apllication in the fields of material science. Recently, researchers have mainly focused on the preparation and relationships between the structures and properties of organic materials with two-photon absorption. In the item, the novel hybrid materials bearing strong two-photon absorption, which are consisted of inorganic and organic moieties, will be obtained to overcome the shortcomings of the organic materials with large conjugation system, multibranches, low solubility and stability. Small organic molecules with synergistic effect as ligands will be designed and synthesized to prepared the novel hybrids having strong two-photon absorption for the application in biology. Based on the connections between the structure and properties, the mechanisms of two-photon absorption process, the combining model between the organic and inorganic moieties, the orbital matched fashion, and the energy transfer pathway will be systematically investigated for the novel two-photon absorbing hybrid materials, combining both the crystal structural determination with theoretical calculations, and using modern techniques, such as time-resolved fluorescene, tunable femotosecond laser and IR spectra in situe et. al.. The following important problems will be solved, such as merged functions, complementary advantages, synergetic effect and tunable fluorescence from organic and inorganic units. The achievements of the research will guide on the design, synthesis, assembly and directed preparation for the excellent hybrids with strong two-photon absorption. The materials will be applied to the areas of ion sensor and bioimaging. The original results will be achieved in the frontier field of the two-photon absorption materials based on the systematic research work.

以应用为导向的构效关系是材料领域中关键科学问题。近年来，人们对有机双光子吸收材料的制备及构效关系进行了较多的研究。本项目以无机/有机杂化双光子材料在生物学中的应用为导向，克服有机材料共轭体系大、枝数多、溶解性差和稳定性低的缺点，设计合成具有协同效应的有机小分子配体，选择不同无机组分为中心体，制备新型无机/有机杂化强双光子吸收材料，探讨其在生物学中的应用。在研究过程中，以构效关系为主线，将晶体结构测试与理论计算结合，利用时间分辨荧光光谱、可调谐飞秒激光光谱和现场红外光谱等先进技术，系统地研究无机与有机组分结合方式、轨道匹配、电子转移机制、能量传递等与双光子效应的关系；解决如何实现无机与有机组分的功能复合、效应协同及发光波段可控等关键问题；制备综合性能优秀的无机/有机杂化强双光子吸收新材料，探索材料在离子识别和生物显影等方面的应用。本项目的系统研究工作将在双光子吸收材料前沿领域取得原创性成果。

以应用为导向的构效关系是材料领域中关键科学问题。本项目以无机-有机杂化双光子材料在生物学中的应用为导向，设计合成具有协同效应的有机小分子配体，选择不同无机组分，制备新型无机-有机杂化强双光子吸收材料，探讨其在生物学中的应用。主要成果如下：.1、设计合成了己基咔唑双酮有机配体和Zn(II)、 Cd(II) 配合物的单晶，利用光电子能谱证实了不同金属离子在配合物中参与电子离域。由晶体结构数据和含时密度泛函理论(TD-DFT)计算了配体及配合物的HOMO、LUMO、吸收光谱、荧光光谱、基态和激发态偶极矩。结果表明：锌配合物在极性溶液中在近红外区显示最大双光子吸收，对活体细胞染色。2、设计合成了近红外三阶非线性光学性质的希夫碱类Pt 配合物TDPt；生物学研究表明它对正常细胞很低的毒性，对人体癌细胞有较强的杀伤作用。双光子生物显影研究结果表明，TDPt 与细胞作用表现出优秀的双光子荧光性质；通过共聚焦显微技术和TEM技术研究了该类顺铂配合物与细胞的作用机理，发现它对人体乳腺癌细胞的溶酶体具有良好的定位效果。该研究成果对研究铂配合物的抗癌机理提供了新的思路。3、设计了系列含硫醚的新型三联吡啶（D-A型）有机配体及其锌配合物材料；系统研究了它们的吸收光谱、荧光光谱、双光子荧光和单线态荧光寿命。此配合物对人体肝癌细胞和斑马鱼组织具有高的识别能力，在双光子激发波长为750nm时，可清晰地定位癌细胞的内质网和斑马鱼的肠道系统。4、设计合成了四种以连接醚氧链三吡啶为配体的锌配合物，发现具有较小共轭体系的配体在配位后有明显的双光子截面增强。发现小分子配合物可以同时着色细胞膜和细胞核；在斑马鱼幼鱼的模型中，发现该分子特异的聚集于中枢神经系统及视网膜系统。在小鼠模型中，尾静脉注射后的小鼠的血脑屏障不仅有效的被标记，而且在脑组织中也大量的发现了该类探针的存在。该研究首次发现了金属荧光配合物对哺乳动物血脑屏障的渗透性，为今后设计类似的荧光诊疗探针提供了重要依据。