Ultrasensitive Detection Of Synthetic Synthesis And Biological Applications Of Hypobromous Acid Fluorescent Probes

Bromine has been reported as the 28th essential element for human health,which can generated hypobromous acid with hydrogen peroxide under the catalysis of heme peroxidase.HOBr is a ROS very similar to HOCl.Moreover,HOBr has strong antibacterial properties,is considered as an important part of the human immune system.But,the excessive generation and accumulation of HOBr in vivo is harmful to organisms and its damaging effects are connected to a wide range of diseases,including,cardiovascular disease,kidney disease,and cancers.Therefore,HOBr,as one of the important reactive small molecules,plays an important role in physiological and pathological processes in organisms.However,the detection method of HOBr is very scarce both in tradition analytical method and fluorescence analysis method.In 2014,Hudson reported that HOBr is an important cofactor in the formation of sulfilimine crosslinks in collagen IV.Inspired by the research,we designed and synthesized two reactive fluorescent probes,and prvovided a new method for further study of the physiological and pathological functions of HOBr.This paper mainly includes the following two aspects of work:1.We synthesized a visible fluorescence probe BPP based on the Suzuki cross-coupling reaction principle for ultrasensitive detection of HOBr,and its application in biological imaging.It was the first time that we develop a reaction-based visible fluorescent probe for imaging HOBr based on a specific cyclization catalyzed by HOBr.The probe itself is small conjugated system.When the interaction with HOBr,HOBr makes the methylthio and amino to form cyclic-sulfilimine.The degree of conjugation system increased and the fluorescence spectra occured red shift greatly.It would avoid the background interference of probe itself,greatly improving the signal-to-noise ratio.Under simulated physiological conditions,the fluorescence intensity of the probe showed a good linear relationship with the concentration of HOBr in the range from 0 to 100 nM.The regression equation was F= 0.48 + 2.64[HOBr]nM,with a linear coefficient of 0.9960.The detection limit(3S/m)was determined to be 17 pM,which is realized to image HOBr with instantaneous,high selectivity,ultrasensitive detection.In addtion,the probe was successfully applied to image native HOBr in HepG2 cells and zebrafish native.2.We chose rhodamine 110 as a fluorophore,and synthesized a mitochondria-targeting near-infrared(NIR)fluorescent probe RhSN-mito for ultrasensitive detection of HOBr.The probe was successfully applied to image HOBr in living cells and zebrafish.When compared to visible light ones,near-infrared(NIR)probes are optimal for biological imaging due to minimal photodamage,deep tissue penetration,and bioautotluorescence avoidance.Under simulated physiological conditions,the fluorescence intensity of the probe showed a good linear relationship with the concentration of HOBr in the range from 0 to 100 nM.The regression equation was F= 0.64+1.94[HOBr]nM,with a linear coefficient of 0.9975.The detection limit(3S/m)was determined to be 20 pM,which is realized to image HOBr with instantaneous,high selectivity,ultrasensitive detection.In addtion,the probe was successfully applied to image native HOBr in HepG2 cells and zebrafish.