Design, Synthesis And Activities Of Phthalocyanine Photosensitizers

In 2012,there were about 14 million new cases of cancer worldwide,about 800million patients died of cancer.Cancer has became one of the key treats to the health of residents,the prevention and treatment of cancer is very grim.Photodynamic therapy?PDT?is a new disease treatment.PDT is lower toxicity,repeatable an higher selectivity compared with traditional cancer treatment.The photosensitizer would accumulate in tumor tissue after intravenous injection into the human body,with the light irradiation of corresponding wavelength,the photosensitizer would cause a series of photodynamic reactions to kill the cancer cells and achieve the effect of treatment of cancer.Because of lack of oxygen in solid tumor,PDT was limited in the treatment of tumors.Thus,the key of improving of the efficacy of PDT is the development of high sensitivity and non oxygen dependent photosensitizer.Because of its excellent photophysical properties and the characteristics of easy to be modified,Phthalocyanine compounds is one of the focus of the study of antitumor.This thesis aims to design,synthesize and screen out cationic silicon phthalocyanine photosensitizer of high sensitivity and non oxygen dependent photosensitizer.The concrete content includes the following aspects:?1?According to the strategy that cationic groups with hydrophobic groups are introduced axially in the matrix of silicon phthalocyanine,three axially substituted siliconphthalocyaninecompoundsaredesignedincludingbis[?3-dimethylaminomethyl-4-hydroxyphenyl?ester)]silicon phthalocyanine iodide?1a?,bis[3-dimethylaminomethyl-4-hydroxybenzene)acetate]silicon phthalocyanine iodide?1b?,bis?3,5-bis-?dimethylamino?methyl-4-hydroxybenzene?ethyl ester)]silicon phthalocyanine iodide?1c?.?2?The target compound 1a-1c were synthesized by condensation,mannich reaction,esterification and methylation with dichlorosilicate phthalocyanine as raw materials.The structures of the target compounds were characterized by 1H NMR,and HRMS.?3?The photophysical properties of target compound 1a-1c were studied.The Q band maximum absorption of compound 1a-1c located at 687nm,688nm,689nm respectively.The fluorescence quantum yield??_F?and singlet oxygen quantum yield??_??of 1a-1c were mesured respectively,with no substitution of zinc phthalocyanine?ZnPc?as the reference,DMSO as solvent.The fluorescence quantum yield is 0.28,0.13,0.23,the singlet oxygen quantum yield is 0.78,0.51,0.54,the inglet oxygen quantum yield produced by the compound 1a is increased 15.6%compared with ZnPc.?4?The interaction of the compound with CT-DNA was investigated by using ultraviolet visible absorption,fluorescence,The binding constant?K?of compound1?a-c?binding to CT-DNA is measured to be 1.55×10⁵ L/mol,1.88×10⁵ L/mol,1.51×10⁵ L/mol.The result show that the three compound may bind with CT-DNA in a mode including outside groove-face binding.?5?The pBR322 plasmid DNA cleavage ability of compound 1a-1c was studied by gel electrophoresis.The result show that the three compounds own good light cutting activity.The order of cleavage ability is same as the singlet oxygen quantum yield.In summary,three axially modified and unreported silicon phthalocyanines were designed and synthesized,its photophysical and photochemical properties and the interaction of the compound with CT-DNA and the cleavage ability to pBR322plasmid DNA was investigated.Compond 1a is an effective ¹O₂ ptotosensitizer and fluorescence quantum yield and good cleavage ability to pBR322 DNA,suggesting that compound 1a is expected to be a photosensitizer with certain development prospects.