Synthesis And Optical Properties Of Fluorescent Probes Containing Oxazopyridine Unit

Due to the advantages of convenience,rapidity,high specificity and sensitivity,fluorescent probes were favored by many scientists.This made the research field of fluorescent probes had been expanding constantly.Nowadays,the application of fluorescent probes in biology and medicine has begun to shine brilliantly.However,most of the existing fluorescent probes had the defects of poor photostability and biocompatibility,which greatly limited their application in biology.Especially,the problem of poor biocompatibility directly affects the biological application,so it is urgent to solve this problem.In recent years,most scientists have also studied the improvement methods on this problem,in which structural modification was the common method.In recent years,most scientists have continued to investigate this issue in the hope of developing improved methods,among which structural modification was a commonly used method.However,this method often involved complex synthetic methods and low efficiency.Considering that nitrogen heterocycles are an essential part of most drug molecules,their excellent biocompatibility is beyond doubt.In view of this,nitrogen heterocycles with good biological activity were introduced into the design of fluorescent probes in order to improve the biocompatibility of probes or markers.In this paper,based on a large number of studies,oxazo[4,5-b]pyridine heterocycle unit and similar units with excellent biological activity were selected as the basic scaffold of fluorescent probes,which were mainly divided into four parts.The specific research contents were as follows:1.Fluorescent probes la-c were obtained by linking oxazo[4,5-b]pyridine heterocycle with three photogenic precursors(coumarin,triphenylamine and phenothiazine)via double bonds.Probes la-c had large Stokes shift(up to 224 nm),high fluorescence quantum yields(83%,37%,75%in tetrahydrofuran,respectively)and excellent photostability.In addition,cytotoxicity test showed that probes la-c had low cytotoxicity.Meanwhile,cell imaging showed that probes lb-c could specifically locate in lipid droplets in cells,and probe la had the ability of dual organelle targeting mitochondria and lipid droplets,so oxazo[4,5-b]pyridine unit could improve the biocompatibility of fluorescent probes.2.In order to improve the biological activity of probes and reduce aggregation,four novel fluorescent probes 7a-d were synthesized by using 1-iodooctadecane protonated oxazo[4,5-b]pyridine unit as sacffolds and four photogenic precursors with excellent optical properties.The modified probes had high photostability(over 80%),obvious solvation effect and low cytotoxicity,and could be specifically located in the cell membrane.Meanwhile,the optical test of probes 7a-d showed that the introduction of oxazo[4,5-b]pyridine unit reduced the possibility of the probes away from aggregation in the solution.Moreover,the time-dependent test of the probes showed that the introduction of oxazo[4,5-b]pyridine unit could extend the retention time of the probes from about 10 min of the commercial cell membrane fluorescent marker(DiO and DiD)to more than 3 hours,which was of great significance to further study the cell membrane.3.On the basis of the previous chapters,a series of red endoplasmic reticulum fluorescent probes 8b-d were synthesized by combining alkyl chains of different lengths with oxazolo[4,5-b]pyridine units and then linking the derivatives with coumarin.Probes 8b-d showed excellent selectivity and low cytotoxicity.Importantly,after 30 min of continuous laser confocal irraditations,the fluorescence of probes 8b-d had no obvious change,which indicated that the probes had excellent anti-photobleaching.In addition,probes 8b-d appeared to be highly sensitive to viscosity.4.Based on the studies in previous three parts,we expanded the types of nitrogen hetercycles and further studied the cell membrane probes.By linking benzaldehyde with benzoindole,benzoxazole and benzothiazole,three viscosity sensitive fluorescent probes 11a-c were obtained.Probes 11a-c had high photostability and low cytotoxicity.Moreover,probes 11a-c showed OFF-ON response to viscosity at 563 nm,599 nm and 601 nm respectively,which exhibited high viscosity sensitivity and specificity.