Design And Analytical Application Of Hypobromous Acid Specific Fluorescent Probe

Hypobromic acid（HOBr）is not only an important reactive oxygen species（ROS）in biological systems,but also one of the key components of host defense system of neutrophils.Eosinophil Peroxidase（EPO）,hydrogen peroxide（H₂O₂）and bromine ion（Br^-）can be used to release HOBr.Although the formation of HOBr is critical to the immune response,and at certain concentrations HOBr can effectively fight off pathogen invasion,excessive production of HOBr can cause damage to host tissues and lead to a range of diseases,including cardiovascular disease,cancer,asthma,neurodegenerative diseases,Alzheimer’s disease,kidney disease,cystic fibrosis,and inflammatory bowel disease.Compared with other biological detection technologies,fluorescence imaging technology has become an indispensable tool for intracellular biomolecular monitoring due to its characteristics of high sensitivity,rapid response,real-time in-situ and non-invasive measurement,and has certain advantages and potential in tracking pathophysiological microenvironment changes.In order to study the physiological and pathological processes involved in endogenous reactive species,various fluorescent probes have been developed and widely used in biological disease models.But so far,there are few reports of small molecule fluorescent probes for intracellular HOBr detection.Therefore,the design and synthesis of fluorescent probes with good selectivity and sensitivity to HOBr is of great significance for the study of the biomedical function of HOBr.With its strong oxidation and antibacterial action,HOBr can effectively kill bacteria,viruses and other microorganisms in water samples,inhibit the growth and reproduction of a series of biofilms caused by bacteria,and then slowly remove biofilms,finally achieving the purpose of purifying water samples.However,the residual HOBr in water samples not only causes certain harm to the environment,but also has certain carcinogenic risk to human body.Therefore,the detection of HOBr residues in water samples is particularly important.Based on this,this thesis designed and synthesized three new HOBr fluorescent probes using quinoline-malonitrile and naphthalimide as the matrix respectively.First,the response ability of these three probes to HOBr was studied.It was then used to detect HOBr in Myocardial ischemia reperfusion injury（MIRI）cell models and in water samples with satisfactory results.Specific research work is as follows:（1）Two kinds of fluorescent probes QM-S and QM-Se with aggregation-induced emission（AIE）characteristics were designed and synthesized.Probe QM-S and QM-Se can form S=N/Se=N bonds by HOBr-mediated S/Se ether cyclization,which is accompanied by a significant reduction in fluorescence.Probes QM-S and QM-Se have good photostability,good dispersion in aqueous biological systems,good selectivity to HOBr,high sensitivity,and low cytotoxicity.The application of probe QM-S and QM-Se to the monitoring of changes in endogenous HOBr levels demonstrated a significant increase in HOBr content in cardiomyocytes during MIRI.MIRI is effectively alleviated by drugs that inhibit oxidative stress,inflammation and iron death processes.Based on this,the probe shows good application potential in the evaluation and screening of anti-miri drugs.（2）A HOBr"off-on"fluorescent probe NDI-Se-1 based on naphthalimide matrix was designed and synthesized.By specific oxidation of HOBr,probe NDI-Se-1 was transformed from Selenoether derivatives to selenium oxide,and its fluorescence was significantly enhanced.Probe NDI-Se-1 has good selectivity,stability and sensitivity to HOBr.The portable quick test strip was prepared by the probe,and HOBr in aqueous solution was determined with good results.