新型潜在近红外类卟啉光敏剂的设计、合成和性能研究

Photosensitizers are the key factor in Photodynamic Therapy. Their tumor selectivity, dark toxicity, singlet oxygen quantum yield and excitation (absorption) wavelength determine the effect of the treatment. Near-Infrared light with a wavelength of 800nm penetrate the longest distance through human tissue. For such a reason, Near-Infrared absorbing porphyrinoid photosensitizers play critical roles and have a great potential in the fields of Photodynamic Therapy. On the basis of the Structure-Property relationship of known porphyrinoids, we have designed a serial of novel putative Near-Infrared absorbing porphyrinoids and will focus our efforts on synthesizing and studying the novel Texaphyrin derivatives, novel porphyrin isomers, novel expanded porphycenes and their conjugates. Our long-term goal is to develop useful therapeutical Near-Infrared photosensitizer drugs. We expect that this research will yield a serial of compounds with great potentials. It is also expected this research will deliver helpful support and provide solid basis for the future development of porphyrin chemistry.

光敏剂是光动疗法最关键的因素，其肿瘤选择性、暗毒性、单线态氧产率和最大激发波长（即吸收波长）直接决定光动疗法的效果。波长为800nm左右的近红外光对人体组织的穿透性最强，所以具有近红外吸收性能的类卟啉光敏剂在光动疗法领域有着重要的应用和巨大潜力。本项目在分析已知卟啉光敏剂的基础上，综合卟啉类似物的结构和性能关系，设计了一系列新型近红外吸收类卟啉化合物，并将聚焦合成和研究新型德州卟啉衍生物、新型卟啉异构体、新型扩展卟啉烯及它们的二聚体。我们的长远目标是最终发展出具有实际应用价值的近红外光敏剂药物。这一研究不但可以产生一批具有潜在应用前景的化合物，还能给该领域未来的发展提供支持和奠定基础。

由于波长为800nm左右的近红外光对人体组织穿透性最好，吸收波长在800nm左右的类卟啉化合物在光动疗法、生物成像等方面有着重要的应用。本项目致力于探索新型类卟啉化合物的合成，以找寻新型近红外吸收化合物，特别是适合于光动治疗的光敏剂药物。我们在分析已知医用光敏剂的基础上，尝试合成了喹喔啉并环扩展卟啉烯、双N-反转卟啉、咔唑德州卟啉衍生物、呋喃杂化Orangarin、噻吩杂化八卟啉、萘啶杂化八卟啉等类卟啉化合物，得到一批新型类卟啉及衍生物，其中既有具有近红外吸收性质的噻吩杂化八卟啉、双N-反转卟啉衍生物，也有具有良好超分子识别性能的萘啶杂化多吡咯化合物、扩展原卟啉烯、哒嗪杂化的Rosarin等新型化合物。本项研究为进一步探索新型潜在光敏剂打下了基础。