【作者】 陈楚珺；

【导师】 黄齐茂；

【作者基本信息】 武汉工程大学 ， 制药化学， 2018， 硕士

【摘要】 卟啉化合物具有好的光敏性,能够作为光动力疗法中的光敏剂,被广泛的应用于癌症的治疗,具有广阔的应用前景。本文以吡咯和苯甲醛为原料,合成5,10,15,20-四苯基卟啉,以此为母体通过对卟吩环中β位选择性硝化,得到β-硝基四苯基卟啉,并对硝基进行还原反应生成β-氨基-四苯基卟啉,在此基础上与甲醛反应,得到了β位桥连双卟啉化合物,并合成了对应的金属配合物。对中间体和目标产物通过质谱、核磁共振氢谱和中红外光谱和拉曼光谱等表征手段对其结构进行分析;通过循环伏安法对中间体的电化学性质进行分析;利用紫外-可见吸收光谱、荧光发射光谱对中间体和产物的光学性质进行研究;利用紫外-可见吸收光谱测定单线态氧、紫外-可见光谱滴定法和荧光光谱滴定法对目标化合物的生物活性进行了研究。本文的主要工作如下:(1)以吡咯和苯甲醛为原料,丙酸为溶剂,合成5,10,15,20-四苯基卟啉;(2)以5,10,15,20-四苯基卟啉为原料,使用醋酸铜以N,N’-二甲基甲酰胺为溶剂合成金属铜离子配位的5,10,15,20-四苯基铜卟啉;(3)以5,10,15,20-四苯基铜卟啉为原料,以醋酸、醋酸酐和氯仿为溶剂与硝酸铜反应,对卟吩环的β位选择性硝化,得到β-硝基-5,10,15,20-四苯基卟啉;(4)以β-硝基5,10,15,20-四苯基铜卟啉为原料,与硫酸反应得到β-硝基-5,10,15,20-四苯基卟啉;(5)以β-硝基-四苯基卟啉为原料,与氯化亚锡反应得到还原产物β-氨基-5,10,15,20-四苯基卟啉;(6)以β-氨基-5,10,15,20-四苯基卟啉为原料,与醋酸铜以N,N’-二甲基甲酰胺为溶剂,反应得到β-氨基-5,10,15,20-四苯基铜卟啉;(7)以β-氨基-5,10,15,20-四苯基卟啉为原料,氯仿为溶剂与甲醛发生缩合反应,得到β-桥连双卟啉化合物。并以此为原料,分别与乙酸铜,乙酸镍反应生成铜卟啉和镍卟啉;(8)通过分离提纯,对中间体和产物通过核磁共振氢谱、质谱和红外光谱等手段对其结构进表征和分析;(9)通过循环伏安法和拉曼光谱对卟啉中间体的性质进行研究;(10)通过紫外-可见吸收光谱和荧光发射光谱分析取代基、溶剂、浓度对卟啉化合物光学性质的影响;(11)以1,3-二苯基异苯并呋喃为活性氧捕捉剂,通过紫外分光光度计来检测卟啉化合物在远红外光的照射下,产生单线态氧的能力,发现β-桥连双卟啉衍生物具有良好的单线态氧的能力;(12)通过紫外可见吸收光谱滴定法测定β-桥连双卟啉衍生物与小牛胸腺DNA的结合模式和结合程度,分析其发生了表面自堆积的外部键合;(13)通过荧光光谱滴定法,使卟啉化合物与小牛胸腺DNA结合后,结论得出其会导致卟啉化合物荧光发射光谱的动态猝灭。更多还原

【Abstract】 As a good light sensitivity,porphyrin can be used as photosensitizer in photodynamic therapy and treatment of cancer with a broad prospect of application.In this paper,5,10,15,20-tetraphenyl porphyrin was synthesized by pyrrole and benzaldehyde.Then,the β-nitro-tetraphenyl porphyrin was obtained by selective nitrification in porphyrin ring,and the β-amino-tetraphenyl porphyrin was generated by nitro reduction reaction.On this basis,beta bit-bridged double porphyrin compounds were synthesized by formaldehyde through condensation reaction.Further,a series of porphyrin complexes with metal ions were synthesized by metal complex reaction.Moreover,intermediates and target products were characterized through hydrogen nuclear magnetic resonance,mass spectro metry,middle infrared spectrum and raman spectroscopy.What’s more,Electrochemical properties were studied by cyclic voltammetry.When determined the ability of singlet oxygen generation,we tested it through ultraviolet-visible spectroscopy.In the end,the biological activity of target products with DNA were tested through ultraviolet-visible spectroscopy titration method and fluorescence spectroscopy titration method.The main works of this dissertation are composed as follows:(1)5,10,15,20-tetraphenyl porphyrin was synthesized as raw materials by distillation of pyrrole and benzaldehyde,acrylic acid as solvent.(2)Center core metal ligand 5,10,15,20-(copper)tetraphenyl porphyrin was prepared with 5,10,15,20-tetraphenyl porphyrin and Cupric Acetate Monohydrate in solvent of N,N’-dimenthyl formaide.(3)5,10,15,20-(copper)tetraphenyl porphyrin was taken as raw materials to react with acetic acid,acetic anhydride,copper nitrate in the solvent of chloroform,finally,theβ-nitro-5,10,15,20-(copper)tetraphenyl porphyrin was synthesized.(4)Using β-nitro-5,10,15,20-tetraphenyl copper porphyrin as raw material,then,put it react with sulfuric acid to obtain β-nitro-5,10,15,20-tetraphenyl porphyrin.(5)β-nitro porphyrin as raw material,was reacting with stannous chloride to getβ-amino-5,10,15,20-tetraphenyl porphyrin.(6)β-amino-5,10,15,20-(copper)tetraphenyl porphyrin was synthesized byβ-amino-5,10,15,20-tetraphenyl porphyrin which was regarded as raw material reacting with copper acetate.(7)The β-amino-5,10,15,20-tetraphenyl porphyrin was taken as raw meterial to react with formaldehyde,then β-aminoporphyrin derivatives were obtained by the condensation reaction.Based on that,the copper-porphyrin and nickel-porphyrin were generated by the reaction of copper acetate and nickel acetate respectively.(8)The structure of intermediates and target products were characterized by hydrogen nuclear magnetic resonance,mass spectrometry and infrared spectroscopy.(9)The properties of intermediates were studied by cyclic voltammetry and Raman spectroscopy.(10)The effects of substitutions and solvents on the optical properties of porphyrin compounds were analyzed by ultraviolet-visible spectroscopy and fluorescence emission spectroscopy.(11)1,3-Diphenylisobenzofuran as an active oxygen scvenger,the ability to produce singlet oxygen was detected by ultraviolet spectrophotometer to detect the porphyrin compounds under the irradiation of far-infrared light,it was found that theβ-aminoporphyrin derivatives had good single-line oxygen capacity.(12)After determining the combination of porphyrin compounds and calf thymus DNA by ultraviolet-visible spectrometric titration,we found their combination mode was the external bond which has been deposited on the surface.(13)Fluorescence spectrum titration was used to determined the fluorescence quenching degree and quenching patterns of porphyrin compounds with calf thymus DNA.In the end,the conclusion is that it can cause the dynamic surge of the fluorescence emission spectra of porphyrin compounds.更多还原