Synthesis And In Vitro Biological Activities Of Novel Amino And Bisphosphonic Esters Axially Substituted Silicon Phthalocyanines

Because of the hexacoordinated silicon,silicon phthalocyanines(SiPcs)can be subsitituted axially.The functionalization of axial position can improve properties by enhancing steric hindrance.Amine plays crucial roles in a number of cell processes including cell proliferation and differentiation.Bisphosphonic esters can result in tremendous success in anti-tumor treatment in vivo by direct suppression cancer growth through anti-invasive,anti-angiogenic and immunomodulatory actions.It was found that the combination use of a photosensitizer with anticancer drugs could generate synergistic effect and result in significant enhancement of anticancer efficacy,reducing side effects and retarding drug-resistance problem.In this thesis,amino chain of different lengths axially substituted silicon phthalocyanines have been synthesized and characterized.The long amino chain axially substituted silicon phthalocyanine is better.On this basis,we synthesize bisphosphonic esters axially substituted silicon phthalocyanine.We also investigate their photophysical,photochemical and in vitro biological properties.Main contents of the thesis are as follows:1 2-(2-amino ethoxy)ethanol and ethanol amine axially substituted silicon phthalocyanines have been synthesized from dichloro silicon phthalocyanine,which have been characterized through NMR(1H,13C),MALDI-TOF,Element Analysis and IR.2 Absorption spectra show the two SiPcs exhibit good solubility in water except for organic solvents.The fluorescence intensities both increase as the pH decreases.3 In vitro cytotoxicity and fluorescence imaging are carried on Hela cells.The extraction method demonstrates that the long amino chain axially substituted SiPc enhance the cellular uptake,which is corresponding with the intracellular fluorescence results.Bright fluorescence emitted by the SiPcs are observed in mitochondria.The two SiPcs show lower dark toxicity and higher phototoxicity,which means they are promising photosensitizers for PDT.4 Bisphosphonic esters axially substituted silicon phthalocyanine has been synthesized from the long amino chain substituted SiPc,which has been characterized through NMR(1H,13C,31P),MALDI-TOF,Element Analysis and IR.5 Photophysical and photochemical properties show that conjugated bisphosphonic esters motif has little influence on the properties of the SiPc,such as the electronic absorption,fluorescence spectra and singlet oxygen quantum yield.However,fluorescence quantum yield is higher.6 In vitro cell studies are carried on A549 lung cancerous cells and HELF normal lung cells.The extraction method demonstrates that the cellular uptake and intracellular fluorescence of A549 cells are higher than that of HELF cells.Bright fluorescence emitted by the bisphosphonic esters substituted SiPc is observed in mitochondria and lysosome.The conjugate shows higher phototoxicity in A549 cells comparing to that of HELF cells.Bisphosphonic esters substituted SiPc shows higher cytotoxicity upon exposure to red-light than that of the amino substituted SiPc.Under the condition of low concentrations amino substituted SiPc almost shows no dark toxicity,but bisphosphonic esters substituted SiPc show dark toxicity.These results suggest that bisphosphonic esters axially substituted SiPc is a photosensitizer with PDT and chemotherapy.