【作者】 王力；

【导师】 张治国；

【作者基本信息】 哈尔滨工业大学 ， 光学， 2013， 硕士

【摘要】 光动力治疗是光学在生物医学领域应用最好的范例。光动力治疗的关键因素是光敏剂。卟啉则是最常用的一种光敏剂，卟啉具有肿瘤细胞靶向性、荧光性、光敏性三种特性。但其在荧光诊断上存在不足，荧光穿透深度的限制使其只能做表皮组织癌变的诊断，且在荧光诊断中需要防范光敏性带来的细胞杀伤性。为此，本文研究的目的为将具有顺磁性的金属掺杂到卟啉环内，一方面利用卟啉的靶向性，可以使金属卟啉作为人体内部肿瘤核磁成像的造影剂，一方面可以利用稀土和过渡金属特殊的能级结构，通过与卟啉能级间的相互作用，改变卟啉的光学性质，得到具有特定性质的光敏剂。本文系统的研究了金属卟啉的合成、光学性质、光敏性、能级结构及核磁增强性能。进行了金属卟啉合成工艺的研究。建立了以咪唑为溶剂，氩气为保护气的金属卟啉合成工艺，通过研究得到了最佳工艺条件；并以紫外-可见吸收谱作为表征手段，提出了对合成反应进程的评定方法。研究了合成的金属卟啉的光学性质。发现钆卟啉发生了荧光红移现象，分析认为钆卟啉的红移荧光来源于卟啉三重态到基态的跃迁，时间分辨光谱结果证明了这种假设；钕卟啉和钐卟啉的荧光峰位与血卟啉单甲醚的基本一致，表明钕和钐保留了卟啉的荧光性质，但是荧光强度减弱、寿命减小，分析认为钕和钐的能级与卟啉单重激发态能级相匹配，通过能量传递，使卟啉单重激发态电子发生无辐射弛豫，导致荧光减弱、寿命减小；锰卟啉发生了荧光猝灭现象，分析认为锰的能级与卟啉单重激发态能级相匹配，强的能量传递导致荧光消失。开展了金属卟啉的光敏性研究。建立了以DPBF作为单线态氧捕捉剂的光敏性研究体系，并在理论上提出了光敏性评价方法。定义以单位时间DPBF的消耗量为光敏剂光敏性的量度，称之为光敏性强度；结果表明钆卟啉保留了卟啉原有的光敏性强度，而钕卟啉、钐卟啉和锰卟啉则失去了光敏性。分析认为钆因能级较高而没有影响到卟啉的能级性质；而金属卟啉中，钕和钐的能级与卟啉三重态的能级相匹配，通过能量传递，使卟啉三重态粒子数猝灭，从而使之丧失了光敏性；锰卟啉光敏性的消失则来源于其荧光猝灭，电子无法布居其三重态。研究了金属卟啉的核磁增强性能。四种金属卟啉均具有核磁增强性能，其中钆卟啉和锰卟啉核磁增强性能较强。通过本文研究，得到四种金属卟啉化合物：钆卟啉具有荧光性质、光敏性和核磁增强性能；钕卟啉和钐卟啉具有荧光性质、核磁增强性能，不具有光敏性；锰卟啉不具有荧光性质、光敏性，具有核磁增强性能。更多还原

【Abstract】 Photodynamic therapy is one of the best example that optics applies in thebiomedical field. The key of photodynamic therapy is photosensitizer. Porphyrin isthe most commonly used as a photosensitizer. Porphyrin has three characteristicswhich are tumor cells targeting, fluorescence and photosensitivity. But it has a defectin the fluorescence diagnosis that it only could achieve the epidermal tissue cancerdiagnosis because of the penetration depth limit of fluorescence. The cell destructionis also needs to paid enough attention to in the fluorescence diagnosis. Therefore, thepurpose of this study was to take the paramagnetic metal into the porphyrin ring. Onthe one hand, because of the character of tumor cell targeting, this process made themetalloporphyrin as a magnetic resonance imaging contrast agent to diagnose thedeep lying tumor. One the other hand, the special energy level structure of rare-earthmetal and transition metal might change the optical property of porphyrin though theinteraction between the energy levels, and then we could get the photosensitizer withspecific properties. This paper systematically studied the synthesis, optical property,photosensitivity, energy level structure and the performance of nuclear magneticenhancement of metalloporphyrin.The synthetic technology of metalloporphyrin was studied. The optimizedsynthetic technology was established which used imidazole as solvent, argon asshielding gas. The optimum technological condition was obtained This study usedultraviolet-visible absorption spectrum as the representation, and proposed theevaluation method of synthetic reaction process.The optical property of metalloporphyrins was studied. The fluorescence redshift phenomenon of gadolinium porphyrin happened. It was proved that the red shiftfluorescence was due to the transition from porphyrin triplet energy level togroundstate. Time-resolved spectra results proved the assumption. The fluorescence peakposition of neodymium porphyrin and samarium porphyrin were identical to that ofhematoporphyrin monomethyl ether. But the fluorescence intensity intensities gotlower, and the fluorescence lifetime decreased. This proved that the energy level ofneodymium and samarium matched with porphyrin excited state energy level.Radiationless relaxation porphyrin excited state energy level of was presented throughthe energy transfer. This led the fluorescence intensity weakened, and thefluorescence lifetime decreased. Manganese porphyrin happened fluorescencequenching phenomenon. This explained that manganese matched with porphyrin excited state energy level. Strong energy transfer led fluorescence disappeared.The photosensitivity of metalloporphyrins was studied. A photosensitivityresearch system was established which used DPBF as singlet oxygen capture agent.The photosensitivity assessment method was presented in theory. This study definedthe consumption of DPBF as the verdict of photosensitivity intensity. According tothe results, Gadolinium retained the original strength of photosensitivity of porphyrins,neodymium, samarium and manganese made porphyrin lost photosensitivity. Theresult proved that gadolinium did not affect the property of porphyrin triplet energylevel due to the high level distribution. Neodymium and samarium realized matchingwith porphyrin triplet energy level, and then porphyrin triplet particle quenchedthrough the energy transfer. This led porphyrin to lost photosensitivity. Manganeseporphyrin lost photosensitivity due to fluorescence quenching. Electronic could notcloth in the triplet energy level.The nuclear magnetic enhancement performance was studied. The magneticresonance imaging proved that the four metalloporphyrins all had nuclear magneticenhancement performance. The performance of gadolinium porphyrin and manganeseporphyrin were stronger than the other two.Through the studies in this paper, four kinds of metalloporphyrin compoundwere synthetized: gadolinium porphyrin with fluorescence, photosensitivity and theperformance of nuclear magnetic enhancement; neodymium porphyrin and samariumporphyrin with fluorescence and the performance of nuclear magnetic enhancement,without photosensitivity; manganese porphyrin with the performance of nuclearmagnetic enhancement, without fluorescence and photosensitivity.更多还原