Synthesis And Properties Study Of Multiorganelle-Targeting Near-Infrared Viscosity Fluorescent Probes

Organelles,including mitochondria,lysosomes,Golgi apparatus,endoplasmic reticulum etc.,are considered to be micro-organs with specific morphological structures and functions in the cytoplasm.They play a key role in keeping the regular work of the cells.In addition,organelles do not only perform their own functions but also contact with each other.Viscosity plays an important role in biological diffusion processes such as biomolecular interactions,enzyme catalysis,and signal transmission.Abnormal viscosity in organelles will directly affect the diffusion of metabolites and cause the dysfunction of the organelles,which further leads to various diseases.Fluorescent probes provide an efficient means to detect viscosity in vivo owing to their non-invasiveness,fast response speed,simple operation and sensitivity.Among these probes,near-infrared fluorescent probes have received extensive attention due to their advantages such as low background interference and deep tissue penetration.Currently,most of the reported viscosity-fluorescent probes can only target a single organelle or do not reach the near-infrared region.So,it is essential to design near-infrared viscosity fluorescent probes to target multiple organelles.In this paper,a series of fluorescent probes were designed and synthesized to identify the viscosity.The identification performance and bioimaging applications of probes were also investigated.The principal findings are as follows:1.Taking 4’-amino-2’-hydroxyacetophenone as raw material,the multiorganelle-targeting near-infrared viscosity fluorescent probe DHDM was designed and synthesized based on the twisted intramolecular charge transfer theory.The probe DHDM has excellent viscosity detection performance.Under the excitation wavelength of 650 nm,with the increase of the viscosity,the fluorescence intensity of the probe at 710 nm gradually increased due to the hindered rotation of the carbon-carbon single bond.The fluorescence intensity of probe DHDM increased about 260-fold,and the fluorescence quantum yield also increased from 0.012 to 0.636.When log η was in the range of 0.83-2.07,there was a good linear relationship between log I710 and log η.In addition,the probe DHDM also showed good anti-interference and stability.Further cell experiments demonstrated that the probes DHDM,DMPC,DEPC,and DHDV could simultaneously target multiple organelles,and the localization of mitochondria was independent of membrane potential.Besides,drug stimulation experiments illustrated that the four probes could detect intracellular viscosity changes,which provide a simple and effective tool for studying the activity of organelles with changing viscosity signals.2.Using 3-aminophenol and 4-bromo-1-naphthonitrile as raw materials,a viscosity responsive fluorescent probe DCIC containing push-pull electron groups,which can target various organelles was synthesized.The probe DCIC had good selectivity and anti-interference towards viscosity,and displayed good stability under both low and high viscosity conditions.Under the excitation wavelength of 500 nm,the fluorescence intensity of the probe at 630 nm continued to increase as the viscosity of the test system enhanced.When log η was in the range of 0.83-2.07,there was a good linear relationship between log I630 and log η.The fluorescence intensity of probe increased about 180-fold,and the fluorescence quantum yield also increased from 0.009 to 0.197.Besides,the probe DCIC can simultaneously target four organelles including mitochondria,lysosomes,endoplasmic reticulum and Golgi apparatus and locate mitochondria independently of membrane potential.In addition,DCIC can detect lysosome viscosity changes obviously due to the quenching of fluorescence intensity under acidic conditions.