Ligand-regulated Phosphorescent Iridium Complex For Photodynamic Therapy Of Tumor Cells

In recent years,photodynamic therapy has been widely used in the medical field because of its minimally invasive and non-thermal advantages.However,most of the photosensitizers used in PDT treatment need to be improved in their ability to generate singlet oxygen,as well as absorption and emission wavelengths,which have certain limitations on their applications in the biomedical field.The excitation and emission wavelengths of the cyclic metal phosphorescent iridium complex are easy to adjust.At the same time,due to the heavy atom effect of its metal iridium,it is easy to be excited by suitable light and then pass through the intersystem to the triplet state,and transfer energy to the oxygen molecule.Produce singlet oxygen for photodynamic therapy.In order to expand the application of iridium complexes in the field of PDT,this thesis has carried out the following three tasks:In recent years,photodynamic therapy(PDT)has been widely used in the medical field because of its minimally invasive and non-thermal advantages.However,the singlet oxygen generation capacity and excitation wavelength of most photosensitizers need to be improved,which limits their application scope.The metal phosphorescent iridium complex has easy adjustment of excitation and emission wavelengths.At the same time,due to the heavy atom effect of its metal iridium,it is easy to pass through intersystem crossing to realize singlet to triplet state after being excited by light,thereby producing singlet oxygen for Photodynamic therapy.Therefore,in order to expand the application of iridium complexes in the field of PDT,this thesis has carried out the following three tasks:(1)The iridium complex DF-Ir-PTZ containing a phenothiazine structure was designed and synthesized for photodynamic therapy.First,the structure of the iridium complex was characterized by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.The ultraviolet absorption method was used to test the quantum yield of singlet oxygen produced by the iridium complex.The results showed that DF-Ir-PTZ was 0.357 and the control molecule DF-Ir-CHO was 0.040.Through the tests of singlet oxygen and reactive oxygen species,the experimental results show that DF-Ir-PTZ has the ability to produce ¹O₂in cells under light conditions.Finally,five kits for detecting cell viability were used to explore the effect of DF-Ir-PTZ on cell viability under light conditions.The results all showed that DF-Ir-PTZ has low toxicity under dark conditions,but it can be induced under light conditions.In addition,the photosensitizer DF-Ir-PTZ shows high binding affinity to proteins.(2)Based on the work in the previous chapter,BT-Ir-PTZ was designed and synthesized by increasing the degree of conjugation on the main ligand and used for photodynamic therapy.The quantum yield of singlet oxygen produced by BT-Ir-PTZ in the solution was tested by the ultraviolet absorption method.We found that increasing the degree of conjugation on the main ligand of the iridium complex can improve the ability of the photosensitizer to produce singlet oxygen.Similarly,through singlet oxygen and reactive oxygen detection experiments,it is shown that BT-Ir-PTZ has the ability to produce ¹O₂in cells under light conditions.Finally,four kits for detecting cell viability were used to explore the effect of BT-Ir-PTZ on cell activity under light conditions.The experimental results all show that the ¹O₂generated by BT-Ir-PTZ under light conditions induces cell apoptosis.(3)On the basis of the work in chapter 2,five iridium complexes BT-Ir-2CF₃,BT-Ir-2Cl,BT-Ir-2Br,BT-Ir-2NH₂and BT-Ir-2CN were synthesized by maintaining the main ligand and changing the structure of the auxiliary ligand.First,the structures of all iridium complexes were characterized by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.The ability of these complexes to produce ¹O₂and ROS was tested by ultraviolet absorption method,fluorescence emission method and electron paramagnetic resonance technology.The experimental results show that the different substituent groups on the N^N auxiliary ligand of the metal iridium complex will affect the production of photosensitizers.Through the singlet oxygen kit staining fluorescence imaging,it is found that the ability of these five iridium complexes to produce ¹O₂in the cell is consistent with the result in the solution.Finally,a variety of kits for detecting apoptosis were used to explore the effects of BT-Ir-2CN,BT-Ir-2Br,and BT-Ir-2NH₂on cells under light conditions.The results show that these three complexes can generate ¹O₂induces cell apoptosis.In addition,through cell fluorescence imaging,it is found that the complex BT-Ir-2NH₂has a specific staining effect on mitochondria and has excellent photostability in cells,which improves the application potential of BT-Ir-2NH₂in fluorescence imaging.The above research work provides a useful reference for the structural design of iridium complexes in photodynamic therapy.