| Fluorescent probe is a kind of fine chemicals widely used.It has the characteristics of small yield,high technical content,strong commodity and high added value of products.It can be designed as a kit with specific uses according to the specific needs of life science research and clinical medical diagnosis.In virtue of fluorescent probes,we can study the content and distribution of the substance to be tested in cells,tissues and organisms,and reveal the physiological and pathological mechanisms related to the level of the substance to be tested,which plays an important role in the component analysis,mechanism determination,drug screening,diagnosis and treatment of related diseases.Hypochlorous acid(HClO)is a common active oxygen species in living organisms.It has strong oxidizing ability and plays an important role in the life activities of living organisms by participating in various oxidative metabolism and physiological processes.Lipid droplets are intracellular organelles that store lipids and proteins,mainly in adipocytes,hepatocytes,and the adrenal cortex.Lipid droplets are closely related to a variety of metabolic and pathological processes,such as diabetes,obesity,atherosclerosis and cancer.They are biomarkers for clinical studies of related diseases and can regulate numerous biological metabolic processes.The level of HCl O in lipid droplets is closely related to the pathogenesis of various diseases.However,H hypochlorous acid(HCl O),which can be localized in lipid droplets at present,is a common active oxygen species in living organisms.Hclo has strong oxidation activity and participates in a variety of oxidative metabolism and physiological processes,playing an important role in the life activities of organisms.Lipid droplets are intracellular organelles that store lipids and proteins,mainly in adipocytes,hepatocytes,and the adrenal cortex.Lipid droplets are closely related to a variety of metabolic and pathological processes,such as diabetes,obesity,atherosclerosis and cancer.They are biomarkers for clinical studies of related diseases and can regulate numerous biological metabolic processes.The level of HCl O in lipid droplets is closely related to the pathogenesis of various diseases.However,at present,there are few studies on fluorescent probes that can image HCl O in situ in lipid droplets,which makes it difficult to research and develop therapeutic drugs for the pathogenesis of related diseases.Therefore,the development of fluorescent probes that can detect HCl O levels in lipid droplets will contribute to the pathogenesis,diagnosis and treatment of related diseases.Hypobromic acid(HBrO),as one of the common active oxygen species in living organisms,has strong oxidizing ability and plays an important role in the life activities of living organisms by participating in various oxidative metabolism and physiological processes in living organisms.Abnormal HBr O level can cause oxidative damage and metabolic disorders in organisms,leading to the generation and development of a variety of diseases.Currently,studies have shown that inflammation,cardiovascular disease,neurodegenerative diseases and cancer pathological causes are associated with abnormal HBr O levels.However,the concentration of HBr O in organisms is low,and it is easy to be interfered by HCl O,so the detection is difficult.The ratio fluorescent probe has two signal output peaks,which can eliminate background interference and provide more accurate detection results.It has high sensitivity and anti-interference ability.Therefore,the design and synthesis of ratio HBr O fluorescent probes can overcome the existing problems and provide a new direction for the study of the pathological mechanism of related diseases and the design and development of drugs.Based on the above background,this thesis mainly completed the following two parts of research work:(1)Based on the biaryl structure,we first designed and screened the fluorescent dye BA-1 for selective imaging lipid droplets.On this basis,a fluorescent probe BA-HCl O targeting lipid droplet was designed and synthesized to study the distribution of lipid droplet and the change of HCl O concentration during the formation of foam cells.The monothioketone in the structure of BAHCl O can react with HCl O to transform into carbonyl group,which can generate the fluorescent dye BA-1 in lipid droplets,realizing the simultaneous detection of HCl O and lipid droplets.Probe BA-HCl O has the advantages of simple structure,easy synthesis,high specificity and rapid response to HCl O.In cell imaging,the fluorescence of probe BA-HCl O was significantly enhanced when lipid droplets and HCl O were present simultaneously.On this basis,the probe was applied to the foam cell model,and the results showed that the probe could simultaneously image and detect the distribution of intracellular lipid droplets and the production of HCl O,indicating that during the formation of foam cells,intracellular lipid droplets accumulated continuously and the concentration of HCl O gradually increased.The probe BA-HCl O will contribute to the study of foam cell formation and related mechanisms,and provide new clues for the diagnosis and treatment of atherosclerosis.(2)A ratiomatric fluorescent probe BL-HBr O based on the structure of coumarin and benzopyran was found,which could respond to HBr O sensitively,rapidly and selectively to perform ratio fluorescence imaging on intracellular HBr O.The experimental results showed that the response of probe BL-HBr O to HBr O was not interfered by other reactive oxygen species,and the change of intracellular HBr O level was characterized by ratio fluorescence signal,which provided a new fluorescence imaging tool for exploring the physiological and pathological processes involved in HBr O.The specific response mechanism of the probe and its biological application are under further investigation.The probe BL-HBr O will contribute to the study of the pathological mechanism of HBr O-related diseases and provide new ideas for the prevention,diagnosis and treatment of related diseases. |
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