双磷光发射铱配合物作为比率探针用于细胞和活体乏氧检测

Molecular oxygen is important and essential to sustain life. Hypoxia is highly related to many diseases. As a result, detection of and real-time monitoring intracellular oxygen is of great importance in clinical disease diagnosis. Phosphorescent transition-metal complexes have been widely employed in the oxygen-sensing applications because of the efficient quenching of their triplet emissive states by oxygen molecules. However, in addition to oxygen quenching, the phosphorescence intensity is also highly related to the concentration of complexes. As it is difficult to control intracellular concentration of complexes and there is a lack of easy or efficient method to measure the intracellular concentration, the application of these complexes in intracellular oxygen sensing is limited. To address this problem, in this proposed project, we will design novel dual-emissive phosphorescent iridium(III) complexes for real-time monitoring the oxygen content in living cells and small animals. Our proposed iridium(III) complexes will display two phosphorescence bands at different wavelengths. They originated from different triplet excited states with different phosphorescence quantum yields and lifetimes. Since oxygen quenching of longer-lived phosphorescence is more efficient, the intensity ratio of the two phosphorescence bands is used to reflect the oxygen content in the environment. As this ratio is independent of the concentration of complexes, dual-emissive iridium(III) complexes are more suitable for intracellular and in vivo applications. Additionally, as the dual-emission is phosphorescence in nature, the iridium(III) complexes are suitable for time-resolved imaging technologies, in which the autofluorescence is minimized.

生物组织处于乏氧状态预示着多种疾病。因此，对生物体内乏氧的检测在临床医学诊断中十分重要。鉴于氧气可以高效地猝灭磷光，很多磷光过渡金属配合物被用于氧气的检测。但是配合物的磷光强度除了受氧气影响，与配合物浓度也密切相关。而生物体中配合物的浓度很难控制或测量，因此，这些配合物无法胜任生物体内的乏氧分析。为了解决这个问题，在本项目中，我们将设计双磷光发射铱配合物，对生物体内乏氧进行比率法检测。这些配合物展现两个源于不同激发态的发光峰。它们具有独立的发射寿命。由于氧气对寿命较长的发射峰优先猝灭，那么双发射磷光的强度比率可用于反映环境中氧气的浓度。因为磷光比率不受配合物浓度的影响，所以双发射铱配合物更适用于细胞和活体内的乏氧成像。此外，配合物的双发射都是磷光，其发射寿命显著长于生物自发光，因此，可以通过时间分辨成像技术，在时间尺度上区分磷光检测信号和背景荧光，有效地减小生物组织自发光对检测结果的影响。

磷光过渡金属配合物因其优异的光物理与光化学性质，在电致发光器件、光伏电池、信息存储、生物传感等方面的应用成为国际研究的热点，吸引了国内外学者的广泛研究兴趣和科技产业界的广泛关注。其中，磷光铱配合物由于具有发光效率高、发射波长可调、Stokes 位移大、光稳定好等优点，作为一类性能优异的光电功能材料在有机光电子领域具有很好的应用前景，引起了广泛的研究兴趣。本项目围绕磷光铱配合物的激发态性质以及功能应用开展了系统研究并取得重要进展。主要研究内容包括（1）新型双磷光发射铱配合物在乏氧/富氧检测中的应用；（2）多吡啶铱配合物在区分活细胞中内/外源性分析物的应用；（3）含吡啶盐基团的电致磷光变色铱配合物及其在信息存储和安全保护中的应用。在本项目的支持下，项目负责人在Chemical Reviews、Journal of the American Chemical Society、Advanced Materials、Chemical Science、Coordination Chemistry Reviews等期刊发表SCI论文9篇，获授权美国发明专利1项、中国发明专利1项，另有6 项中国发明专利已经公开。部分研究成果获南京邮电大学科学技术奖一等奖（第四完成人）。项目负责人的研究成果获得国内外同行的高度认可，2篇论文入选ESI高被引论文，1篇论文入选ESI热点论文，1篇论文获南京市自然科学优秀学术论文奖。在本项目执行期内，项目负责人获批国家自然科学基金面上项目一项。另外，在本项目的支持下，培养或协助培养了博士/硕士研究生和本科生二十余名。