Regulating The Physicochemical Properties Of Conjugated Molecules And Their Biological Applications

The probe acts as a signal molecule which is widely used in chemical,environmental and biomedical research such as metal ion recognition,biomacromolecule analysis,biomolecular labeling and bioimaging.Because of excellent optical properties,environmental stability and designability,conjugated organic semiconductors become an emerging class of optical probes that exhibit superior applications in biomedical photonics over traditional fluorescent dyes.Generally,the chemical composition and structure of a conjugated organic semiconductor directly determine its important properties of a probe such as ultraviolet absorption wavelength,fluorescence quantum efficiency,energy level,and chemical stability.In order to obtain probe molecules with more targeted functions in biomedical analysis and imaging applications,scientists use rational probe molecular design strategies and effective synthesis methods to optimized the design of the probe so that it has the functions of imaging and therapeutic integration,enhanced biocompatibility,water solubility,and targeting of organelles.Fluorescence imaging is commonly used to analyze molecules and events that occur at subcellular levels,providing high temporal and spatial resolution for non-invasive bioanalytical techniques.Meanwhile,fluorescence imaging is a very important imaging method in clinical medicine that only needs simple instrument,have easy-to-read/recognized signals with high sensitivity.Due to the relaxation of the electron-excited singlet state to the triplet state,the probes not only produce fluorescence emission,but also produce photodynamic effects.Photodynamic therapy has good controllability,low toxic side effects,and can avoid the resistance of tumor cells.However,most organic conjugated semiconductor photosensitizers produce exogenous phototoxicity to non-targeted tissues during imaging;and the yield of ROS are reduced due to molecular packing effects.In order to solve the above problems,three different kinds of organic conjugated semiconducting probes including three different electrical characteristics central structural unit of perylene diimide?PDI?,pyrrolopyrroledione?DPP?and benzo[c][1,2,5]thiadiazole?BT?respectively were designed and sythesized.These probes have been tested on the cell or mouse tumor model for the integration of fluorescence imaging and photodynamic therapy.The research of this thesis mainly includes the following three aspects:1?Bioimaging and photodynamic therapy of perylene diimide derivatives?PDI?.Using the novel perylene diimide derivatives 49-Py and 49-Py-PDI-a to study the related properties of solution and nanoparticles and apply 49-Py-PDI-a NPs to bioimaging and photodynamic therapy.Both in vitro and in vivo experiments have shown that 49-Py-PDI-a NPs can be targeted to the tumor site for fluorescence imaging,and singlet oxygen can effectively kill tumor cells.The generation of singlet oxygen by 49-Py-PDI-a may be caused by molecular distortion and formation of a ruthenium structure.2?Bioimaging and photodynamic therapy of amphiphilic pyrrolopyrroledione?DPP?derivatives.We have successfully synthesized an organic conjugated small molecule pyrrolopyrroledione?DPP?derivative containing a pyridine quaternary ammonium cation.The ethyl bromide is linked by a chemical bond,which effectively solves the problem of solubility of the organic compound in water.Also,due to the binding of the positive lipophilic cation moiety to the mitochondrial negative membrane,ethyl-BD-DPP NPs can target mitochondria.Experiments show that ethyl-BD-DPP NPs have superior photodynamic quantum efficiency up to 52.26%,emission wavelength range is610-680 nm.In addition,cell experiments clearly showed that ethyl-BD-DPP NPs can be fluorescently imaged in mitochondria,and the higher the concentration of ethyl-BD-DPP NPs has the better treatment effect on Hela cells.3?Synthesis,properties and biological applications of water-soluble organic fluorescent dyes benzo[c][1,2,5]thiadiazole?BT?derivatives.In order to control the energy levels and spectra of conjugated organic molecules,we chose benzo[c][1,2,5]thiadiazole?BT?as a structural unit and synthesized a group by inserting a thiophene heteroatom ring synthesizing a set of conjugated organic molecules M₁ and M₂ and comparing their properties.Thereafter,1-?3-trimethylammoniopropyl?-4-methylpyridine dibromide is selected and covalently linked to the molecule M₂,so that weak the accumulation of M₂ and solve the problem of poor solubility of organic small molecules in water.Cell experiments have shown that M3 can produce singlet oxygen in cells and have therapeutic effects on cells,and can effectively perform two-photon fluorescence imaging on cell membranes.