Preparation Of Activatable Near-infrared Fluorescent Probes Based On Xanthene And Their Detection And Imaging Applications

Hydrogen peroxide and alkaline phosphatase are important biomarkers in organisms,which play important roles in the physiological and pathological processes.Real-time detection of the levels of hydrogen peroxide and alkaline phosphatase in organisms is of great significance for promoting in-depth study of their functions in organisms and early diagnosis of diseases.The activatable near-infrared fluorescence probe has the advantages of high sensitivity and can specifically detect these biomarkers.In this paper,two kinds of activatable near-infrared fluorescent probes based on xanthene have been developed to detect hydrogen peroxide and alkaline phosphatase,respectively.The main contents are as follows:(1)A novel activatable near-infrared fluorescent probe TCF-Y-B based on xanthene as the electron donor and tricyanofuran(TCF)as the electron receptor has been designed and synthesized for the detection of hydrogen peroxide.The fluorescent dye TCF-Y-OH is synthesized by Suzuki coupling reaction and then coupled with borate group as the recognition group for hydrogen peroxide to form the fluorescent probe TCF-Y-B.When the probe reacts with hydrogen peroxide,the borate group on TCF-Y-B is turned into hydroxyl,resulting in the departure of the recognition group and releasing the fluorescent dye TCF-Y-OH which emits strong fluorescence at 770 nm.In addition,the selectivity of the probe TCF-Y-B for hydrogen peroxide detection has also been investigated.(2)A xanthene-based AIE-type activatable fluorescent probe QY-Tri-P has been designed and synthesized for the detection of alkaline phosphatase.Based on quinoline(acceptor)and xanthene(donor),the fluorophore QY-Tri is synthesized through Suzuki coupling,Knoevenagel condensation and other reactions,and then a phosphate group is introduced as the recognition unit for alkaline phosphatase to form the probe QY-Tri-P.After the enzymatic reaction of the probe QY-Tri-P and alkaline phosphatase,the phosphate group is cleaved,and thus releasing the fluorescent dye QY-Tri which emits strong fluorescence signal at 780 nm.The probe QYTri-P has low cytotoxicity and good biological safety,and can be used for fluorescence imaging and photoacoustic imaging of endogenous alkaline phosphatase in the mouse model of liver injury induced by acetaminophen(APAP).With the help of three-dimensional MSOT images,accurate positioning of APAP-injured liver regions can be achieved.