New Type Of Phthalocyanine Compounds Synthesis And Activity Of Study

Cancer is one of the major causes of disease and death in the world.Photodynamic therapy(PDT),a cancer treatment method,is paid more and more attention.And it has been widely used in the treatment of lung cancer,esophageal cancer and breast cancer.A nontoxic photosensitizer preferentially accumulates in tumor tissue or vascular and then it will produce singlet oxygen with the irradiation of light of specific wavelength,which consequently induce the production of other reactive oxygen species(ROS).These ROS will lead to damage of cellular components near photosensitizer,and ultimately kill tumor cell through necrosis or apoptosis pathway.The type of light damage depends on photosensitizer's precise positioning in cells.Photosensitizer located in is more attractive in anticancer drug research,because they tend to fight tumor through the mechanism of apoptotic.Obviously,the key factor influencing the PDT is photosensitizer.Although both at home and abroad the photosensitive drug research and development has made gratifying achievements,the development of photosensitizer still significantly lags behind,which is one of the important reasons that the PDT is far from being fully developed.Therefore,the development of effective new photosensitive drugs is an arduous task for scientists.Phthalocyanine compounds,with its easily-modified structure and ideal photophysical and photochemical properties,become the focus of the study of anticancer drug.This paper aims to design,synthesize and select cationic silicon phthalocyanine photosensitizers causing apoptosis with targeting mitochondria.The specific contents include the following aspects:(1)Considering mitochondrial's bilayer lipid membrane structure and the presence of transmembrane potential,seeing silicon phthalocyanine as a nucleus,introducing a cationic group with a hydrophobic group in the axial direction,we designed four silicon phthalocyanine derivative,i.e.bis [(3,5-bis-(trimethylsilyl)methyl-4-hydroxyphenyl)carbonyl] diiodide silicon phthalocyanine(?-a),bis [(2-pyridyl-methyl of N-)ethoxy]diiodide silicon phthalocyanine(?-b),bis [2-((1-methyl)-1-imidazolyl)ethoxy] diiodide silicon phthalocyanine(?-c),bis [2-((N-methyl)-N-morpholinyl)ethoxy] diiodide silicon phthalocyanine(?-d).(2)Using silicon phthalocyanine dichloride as the starting material to react withhydroxy benzyl amine derivatives,hydroxyl ethyl pyridine,hydroxyethyl imidazole and hydroxyethyl morpholine,we get target compounds ?(a-d),and by methylation we get target compounds ?(a-b)whose structure is represented by MS and elemental analysis.(3)The photophysical properties of compound ?(a-d)were studied and compared.Compound ?(a-d)Q-band maximum absorption peak were 678,681,681 and 682 nm.With Zn Pc as reference and DMSO as solvent we test the fluorescence quantum yield of the target compound(?F)and singlet oxygen quantum yield(??).The fluorescence quantum yield of target compounds ?(a-d)is 0.329,0.200,0.308 and 0.253(?FZn Pc=0.2).The singlet oxygen quantum yield in order is 0.83,0.67,0.59 and 0.78(??Zn Pc=0.67).The singlet oxygen quantum yield of compound ?-a and ?-d are higher than that of Zn Pc.(4)The interaction between ?(a-d)and CT-DNA is studied through UV spectra and fluorescence emission under steady-state absorption determination.The binding constants is 1.63 × 10~5,2.32 × 10~5,1.28 × 10~5,1.37 × 10~5L/mol;and the fluorescence quenching constants is 1.10 × 10~5,1.21 × 10~5,1.02 × 10~5,1.14 × 10~5L/mol.The result is gotten by EB method and it shows that the binding way of ?(a-d)and CT-DNA is Ditch outside combination,and the binding capacity is comparable to that of the EB.(5)The ability of the target compound ?(a-b)to cut DNA p BR322 was tested though agarose gel electrophoresis.The order of it is ?-a>?-d>?-b>?-c,which is consistent with their ability to produce singlet oxygen.Among them the compound ?-a can completely cut p BR322 DNA,under the conditions of light 35 min and concentration of 25 M,which may be related to the generation of the active methyl group and the alkylation of DNA.All in all,we have designed and synthesized four silicon phthalocyanine compounds which have not been reported in literature.It also studied their optical physical properties,the interaction with CT-DNA and the ability to cut p BR322 DNA.The compound ?-A with its superior ability of generating singlet oxygen(comparing with Zn Pc)and good cutting p BR322 DNA activity,is expected to become a promising anti-tumor photosensitizer.