近红外多吡咯光敏剂的合成与性质研究

Photosensitizer is the key factor for photodynamic therapy (PDT) which as a minimally invasive tumor therapy combines the photosensitizer, oxygen, and the excitation light to achieve the therapeutic effect. The development of novel photosensitizers that have strong absorption in the near infrared (NIR) region, with high selectivity in the accumulation into cells and with single component has attracted increase research interests in a diverse research fields. In this project, we plan to develop new synthetic methods for the efficient construction of tetrapyrrolic photosensitizers BTP and MTP, study their spectral properties, photochemical stabilities, structure-property relationships, and the underlying mechanism for their illumination and/or singlet oxygen generation properties. Among those, photosensitizers with good photochemical properties will then subjected for the subsequent investigations of their uptake (in cancer cells), subcellular localization, phototoxicity and dark toxicity. Finally, the substituent and electronic effects of the photosensitizers on their optical and photodynamic properties will also be investigate and compared to achieve the lead compound. The success of this project will provide new material for the diagnosis and treatment of disease besides the theoretical support and good reference for the further design of novel polypyrrole-derived NIR photosensitizers.

光动力疗法(PDT)是一种基于光敏剂、氧和激发光的微创肿瘤治疗技术, 其中光敏剂是PDT治疗的关键。发展在近红外区吸收强、能够选择性进入特定细胞、组成单一的新型光敏剂具有重要的科学意义和良好的应用前景。本项目拟发展构建新型近红外四吡咯光敏剂BTP和MTP的高效合成方法；研究目标光敏剂分子的光谱、光化学稳定性、电化学性能及其构效关系与规律性、探索发光/产生单线态氧机制；研究光化学性能良好的光敏剂在癌细胞中的吸收量，亚细胞定位，光毒性和暗毒性；分析比较染料种类，取代基位点和电子效应对于光敏剂光学和光动力学性能的影响，筛选出近红外光敏剂先导化合物,为疾病诊断和治疗提供新材料。该课题将为进一步有效设计含多吡咯的新型近红外光敏剂分子提供理论支撑和有效参考。

光动力疗法(PDT)是一种基于光敏剂、氧和激发光的微创肿瘤治疗技术, 其中光敏剂是PDT治疗的关键。发展在近红外区吸收强、能够选择性进入特定细胞、组成单一的新型 光敏剂具有重要的科学意义和良好的应用前景。本项目利用对多种稳定化的氮富烯的选择性衍生，发展了几种构建具有近红外多吡咯类化合物的高效合成方法（吡咯与卤代BODIPY的SNAr亲核取代反应；吡咯与卤代二吡咯的SNAr亲核取代反应；金属催化的C-H活化等）；发展了系列近红外荧光染料及其高效合成方法；构建了系列红外BTP和BODIPY类光敏剂染料分子并研究了其光化学和电化学性质、光/化学稳定性、单线态氧量子产率以及光动力学性质，研究了取代基对BTP光敏剂光学和光动力学性能的影响。本项目的成果将为发展新型具有近红外吸收的多吡咯类类染料和光敏剂的设计合成和应用提供有效推动。