Design,Synthesis And Biological Application Of Naphthalimide Fluorescent Compounds Based On ICT/TICT/PET Mechanism

The abnormal expression of small molecules in the cell system will affect the normal operation of the physiological activities of the whole life.Due to the complexity of cells,it is not a simple matter to detect changes in small molecules in a specific intracellular system.Fluorescent probes have excellent characteristics such as small molecular weight,easy operation and chemical stability.It usually relies on fluorescence microscopy imaging technology,which can detect,visualize and characterize the morphology and dynamic phenomena of organisms in a multi-dimensional manner at the molecular level,so as to realize the detection and analysis of small molecules in organisms and biological imaging.This is of great significance for the elucidation and lucubration of the mechanism of action of small molecules in life and the relationship with human diseases.At the same time,it promotes the development of biology and medical research.Therefore,in this work,two cases of naphthalimide fluorescent probes based on the linking arm inducing effect to regulate the ICT/TICT/PET mechanism were designed and synthesized,which realized the application value of fluorescent probes in biorecognition and bioimaging.Intracellular p H is an important factor related to cell metabolism and pathological conditions.It is a key biomarker of cell abnormalities and affects the basic life activities of the body.Therefore,it is important to find a suitable method to monitor small changes in p H.In order to be able to monitor the physical and chemical properties of p H changes,a naphthalimide fluorescent probe（NI-OH）was designed and synthesized with a methylene chain as a linking arm for inducing effect and regulating the mechanism of intramolecular charge transfer（ICT）.Spectral experiments show that the fluorescence intensity of the probe NI-OH will change in the presence of different p H values.Cell experiments show that the fluorescent probe NI-OH has negligible cytotoxicity.It can be seen that the probe NI-OH can perform biochemical analysis of p H changes in organisms,and has the potential for cell imaging of p H changes in organisms.The oxidative damage to DNA caused by abnormal levels of hydrogen sulfide in cells is closely related to human diseases.Therefore,it is of great significance to establish a new type of visual detection and analysis method for the oxidative damage caused by hydrogen sulfide to DNA in vivo.Based on a series of previous studies,this work has designed and synthesized a series of fluorescent probes（NT-N₃-1,NT-N₃-2,NT-N₃-3）with naphthalimides as fluorophores,methylene chains of different lengths as link arms,and azide groups as recognition groups.With NT-N₃-2 and NT-N₃-3 as the contrast molecules,the fluorescent probe NT-N₃-1 can achieve high-efficiency and specific binding of hydrogen sulfide-DNA,so as to detect DNA damage caused by hydrogen sulfide in biological systems.When the probe molecule NT-N₃-1 is in a free state in the solution,the molecule undergoes photo-induced electron transfer（PET）,and the fluorescence is very weak.When the molecule encounters the hydrogen sulfide-DNA dual target molecule,the probe molecule promotes the molecule’s intramolecular charge transfer（ICT）and twisted intramolecular charge transfer（TICT）through the coordinated changes of the structure and conformation of its recognition group,achieving simultaneous specific detection of H₂S and DNA oxidative damage caused by H₂S in biological systems.