Synthesis And Properties Research Of Near-Infrared Fluorescent Probes For Fe²⁺ Based On N-oxide Chemistry

Iron is an important transition metal in biological systems,involving in many important physiological processes.Under physiological conditions,iron mainly exists in Fe2+and Fe3+.Abnormal Fe2+ concentration may affect many disease processes,such as cancer,Alzheimer’s disease and Parkinson’s disease.Hence,the development of a method that could efficiently detect Fe2+ in vivo is of great significance.Optical imaging of fluorescent metal ion probes have attracted extensive attention.Near-infrared(NIR,650-900 nm)fluorescent probes are widely used in vivo imaging because they can penetrate relatively deeply into tissues,low autofluorescence background and cause less damage to biological samples.In this thesis,we used N-oxide bond as a recognition site and developed two fluorescent probes for detection of Fe2+.The main research work is as follows:Based on N-oxide chemistry,we designed a near-infrared fluorescent probe DCI-Fe(II)for detection of Fe2+.The probe uses the dicyanoisophorone derivatives as fluorophore and N-O bond as a recognition site to detect Fe2+ through the Fe2+-mediated deoxygenation.DCI-Fe(II)shows highly selective turn-on near-infrared(NIR)fluorescence(～120-fold enhancement at 700nm)for Fe2+ with a rapid response(5 min),high sensitivity(51 nM of detection limit),and large Stokes shift(195 nm).Moreover,the probe has low cytotoxicity and can be used to real-time monitor exogenous and endogenous Fe2+ in living cells.DCI-Fe(II)also exhibits excellent NIR fluorescent bioimaging ability in the lipid droplets.With the probe,it was confirmed that the content of endogenous Fe2+ in cancer cells is higher than that in normal cells.More importantly,the probe can be used for the detection of Fe2+ in mice.Based on the above results,we further developed a ratiometric and near-infrared fluorescent probe for the detection of Fe2+.The piperazinyl group is used to connect coumarin and dicyanoisophorone derivatives to construct the fluorophore based on the FRET mechanism,and the N-O bond was also used as the recognition site.Fluorescent probe NRF-Fe(Ⅱ)shows high selectivity and sensitivity for the detection of Fe2+,accompanied by distinct ratiometric and near-infrared fluorescence signal change.In addition,NRF-Fe(II)can be used to real-time monitor exogenous and endogenous Fe2+in living cells and detects Fe2+ in mice.Moreover,probe NRF-Fe(II)can be used to monitor Fe2+ level in drug-induced liver injury.