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1、I摘要磁共振成像(magnetic resonance imaging, MRI)是一种利用生物体不同组织在外磁场影 响下产生不同磁共振信号来成像的先进的医学影像诊断技术。为确保临床诊断的准确性， 30%以上的MRI诊断需要采用合适的MRI造影剂来提高成像对比度。由于卟啉类化合物 能选择性地富集于肿瘤组织，且与金属离子络合得到的金属卟啉类配合物的特殊结构具有 抗肿瘤作用，已被广泛用作对肿瘤的光动力治疗。由于顺磁性金属卟啉化合物具有较强的 磁共振成像(MRI)造影信号，自20世纪80年代初开始，顺磁性金属卟啉化合物就被广泛 用于“肿瘤搜寻(tumor-seeking)”研究，被认为是一类“肿瘤特
2、异性” MRI造影剂，有可 能成为兼有磁共振成像与光动力治疗双功能的潜在诊断药物。本文采用天然零毒性的窄分子量分布的低聚壳聚糖对卟琳类化合物(四羧基苯基锰卟 啉，Mn-TCPP)进行了修饰，合成了一系列卟啉-壳聚糖衍生物并研究了其体外弛豫性能， 主要包括以下几个部分：1.初步介绍了卟啉类化合物的合成及顺磁金属卟啉在磁共振成像领域的研究进展，然 后简要介绍了壳聚糖的性质、降解手段及其应用。2.合成了一系列不同聚合度的窄分子量分布的低聚壳聚糖(CS)修饰的四(4-羧基苯基） 锰(II)卟啉(Mn-TCPP)金属配合物作为一种潜在的磁共振成像(MRI)造影剂，发现该系列金 属卟啉-壳聚糖衍生物均有良
3、好的水溶性。利用红外光谱(FTIR)，紫外光谱(UV-vis)及电感 耦合等离子体发射仪(ICP-AES)等对其结构进行了表征。结果表明，窄分子量分布的低聚壳 聚糖通过酰胺键与Mn_TCPP键连。研究了配合物(Mn-TCPP-CS，n=6, 8, 20)的体外弛豫性 能，结果发现，这类造影剂的弛豫性能均高于商用磁共振成像造影剂Gd-DTPA。初步的研 宄表明Mn-TCPP-CS可作为潜在的具有肿瘤靶向性的磁共振成像造影剂。3. 采用聚合度为20的窄分子量分布的低聚壳聚糖(CS20)修饰含有不同金属离子(Fe3+， Co2+，Ni2+，Cu2+，Zn2+)的金属叶啉配合物，合成了一系列金属0卜啉
4、-壳聚糖化合物，研宄发现 该系列金属卟啉配合物均具有良好的水溶性。采用FT-IR，UV-vis，ICP-AES和质谱(MS) 对其结构进行了表征。此外，本文还合成了一些不对称卟啉化合物，重点研究了其紫外光 谱和荧光性能。江 苏 大 学 硕 士 学 位 论 文II关键词：卟啉，低聚壳聚糖，磁共振成像造影剂，弛豫率卟啉-壳聚糖衍生物的制备及性能研究ABSTRACTMagnetic resonance imaging (MRI) is a medical imaging diagnostic technique, which makes different organisms show differ
5、ent magnetic resonance signal under external magnetic fields. In order to improve diagnostic accuracy, more than 30 percent of MRI diagnosis is accompanied with MRI contrast agents to improve the quality of image. Prophyrin and its derivatives can be selectively concentrated in tumor tissues and met
6、alloporphyrins with special composition can act as anti-cancer drugs, which has been widely used in photodynamic therapy (PDT). Since 1980, paramagnetic metalloporphyrins were originated as tumor-seeking, because paramagnetic they have high magnetic resonance imaging contrast signal. The metalloporp
7、hyrins have been considered to be tumor-targeting contrast agents, which has the advantage of becoming potential diagnostic drug with MRI and PDT diflincdonality.In this paper, a series of functional complex porphyrin-chitosan derivatives Mn-TCPP-CS were synthesized as a potential MRI contrast agent
8、 was synthesized through naturally non-toxic CSn with narrow molecular weight distribution modifying with Tetra(4-carboxyphenyI) Mn(II)-porphyrin (Mn-TCPP). The main contents are divided into following parts.1.The synthesis of porphyrins and the researching progress of paramagnetic metalloporphyrins
9、 in the field magnetic resonance imaging were preliminary summarized. Then the properties of chitosan, the method of chitosan degradation and its application were introduced.2.A series of Tetra(4-carboxyphenyl) Mn(II)-porphyrin (Mn-TCPP) complexes Mn-TCPP-CSrt (n=6, 8, 20) modified using low molecul
10、ar weight chitosan with narrow molecular weight distribution as potential magnetic resonance imaging (MRI) contrast agents were synthesis. The synthesized Mn-TCPP-CS (n=6, 8? 20) showed high water-solubility. The chemical structures were characterized by fourier transform infrared spectra (FTIR), UV
11、-vis spectra, and inductively coupled plasma atomic emission spectrometry (ICP-AES), etc. The characterization results showed that Mn-TCPP was successfully linked to CSrt by an amide bond The relaxation properties in vitro of Mn-TCPP-CS were studied. The results indicated 江 苏 大 学 硕 士 学 位 论 文that the
12、 relaxivity of the synthesized Mn-TCPP-CS provided higher relaxation performance than that ofncommercial contrast agent Gd-DTPA. These preliminary studies suggested that Mn-TCPP-CS had the advantage of becoming a potential tumor-targeting contrast agent.3.A series of metaI(Fe3+, Co2+, Ni2+, Cu2+? Zn
13、2+) porphyrins modified using low molecular weight chitosan with 20 degree of polymerization (CS2)and narrow molecular weight distribution were synthesized. The results suggested that all of these complexes showed high water-solubility. The chemical structures were characterized by fourier transform
14、 infrared spectra (FTIR)，UV-vis spectra, and inductively coupled plasma atomic emission spectrometry (ICP-AES), etc. Some unsymmetrical porphyrins were also synthesized and the properties of UV-vis and fluorescent spectrum were studied.KEY WORDS: Porphyrin, Low molecular weight chitosans, Magnetic resonance imaging contrast agent, Relaxivity江 苏 大 学 硕 士 学 位 论 文HI卟啉-壳聚糖衍生物的制备及性能研宄IV目录m-M % ife.iu卟啉类化物简介 .1 1丄1卟啉类化合物的合成方法.2 1 1.1 1 Rothemund 法 .2 1.1.1.2Adler-Longo 法 .2 1.1.1.3Lindsey 法 .3 1.1.1.4郭灿城法.3U. 1.5微波激励法.3 1.1.1.6 2+2法 .4 1.1.1.7 3+1法 .
