Synthesis And Bioactivity Study Of Novel Conjugated Porphyrins

Photodynamic therapy(PDT)as a new treatment of cancer had little side effects and high security,comparing with surgery,chemotherapy and radiotherapy.The porphyrin was one of the important type of photosensitizers.Porphyrin and its derivatives,known as the "color of life",bearing a stable and conjugated macrocyclic structure,play an important role in the life activities.This thesis includes main parts as follow:1.The synthesis methods and the characteristics of porphyrin were introduced.The binding mode of porphyrin and DNA was studied.The photochemical,photophysical and anti-tumor mechanism of PDT,and the development of photosensitizers were briefly describled.The properties and applications of ruthenium complexes,1,10-phenanthroline and asymmetric porphyrins were reviewed.2.Five new porphyrin compounds and their intermediates were synthesized and characterized by UV,1H NMR,MS and IR sepctrum.Specifically,the phenanthroline was conjugated with porphyrin structure through the imidazole ring,which will increase the conjugation degree of the system.Meanwhile,the water-solubility of system was improved after linking with the rutheniumcomplex.In order to improve the hydrophobic / hydrophilic balance of system,the imidazole ring was modified with butane or octadecane.3.The binding mode of DNA and porphyrins was studied by UV-visible absorption,fluorescence and cirucular dichroism spectroscopy.The results shown that porphyrin 1 interacted with DNA in a outside binding manner,porphyrin 2 and 3 in the way of outside stacking,while porphyrin 4 and 5 in an intercalative interaction manner.The binding ability of porphyrin 5 was the strongest while porphyrin 3 was the weakest.4.The singlet oxygen quantumn yield of the synthesized porphyrin was determined by DPBF method.The porphyrin 5 had a higher singlet oxygen quantumn yield related to other four compounds,which was 3.5 times that of H2 TPP.As the metal copper centre will decrease the conjugation of porphyrin macromolecular,porphyrin 3 and 4 had a low yield of singlet oxygen.5.The DNA cleavage ability of the porphyrin compounds was evaluated by the agarose gel electrophoresis.The results indicated the porphyrin-based ruthenium complexes 5 with concentration of 40 ?mol/L,could completely cleavage the DNA.However,the DNA cleavage ability of porphyrins 1,2 and 3 was very weak.In summary,the porphyrin-based ruthenium complex 5 is expected to be used as a potential photosensitizer due to the strong interaction with DNA,which will provide a basic fundation for the following cell research.