CN-122010916-A - Targeted Golgi AIE ionic probe, preparation method and application

Abstract

The invention provides an aggregation-induced emission (AIE) ionic probe (E) -4- (2- (5- (4- (diphenylamino) phenyl) thiophene-2-yl) vinyl) -1- (4-sulfanylbenzyl) quinoline-1-onium hexafluorophosphate (V) salt of a targeting Golgi apparatus, namely a fluorescent probe TTQ-GA, a preparation method thereof and application thereof in detection. The benzenesulfonamide group of the probe has selective combination on a golgi protein cyclooxygenase 2 (COX-2) inhibitor SC-558 to realize golgi targeting, the hydrophobic triphenylamine part of the probe and the hydrophilic quinoline cation part of the probe enable the probe to have amphipathy, the probe does not emit fluorescence in aqueous solution, the probe can emit strong fluorescence when the molecular movement is limited and excited, the washing-free marking of the golgi is realized, the probe generates a large amount of ROS under the excitation of light, the local lipid peroxidation of the golgi is promoted to be increased, and the apoptosis of cancer cells is promoted.

Inventors

• XUE KE
• CHEN YUNYI
• WAN WENJUN
• WU QI
• ZHOU YU
• LI CHANGQING
• XU YIFAN

Assignees

• 盐城师范学院

Dates

Publication Date

20260512

Application Date

20260201

Claims (5)

1. 1. An ionic probe of Golgi apparatus targeted Aggregation Induced Emission (AIE) is characterized in that the ionic near infrared fluorescent probe has a chemical structural formula as follows: 。
2. 2. The method for preparing the Golgi apparatus targeted aggregation-induced emission ionic probe according to claim 1, wherein 5- (4- (diphenylamine) phenyl) thiophene-2-carbaldehyde (TTC), piperidine and 4-methyl-1- (4-sulfonamide benzyl) quinoline-1-onium hexafluorophosphate (V) (Q-SBN) are placed in a reaction bottle, ethanol is added into the reaction bottle, the mixture is heated to not lower than 85 ℃ under the protection of nitrogen, the reacted reaction solution is cooled to room temperature, the organic phases are extracted and combined, drying and reduced pressure concentration treatment are carried out, a crude product is obtained, dichloromethane/methanol is used as an eluent, and the crude product is purified by a column chromatography method, so that fluorescent probe (E) -4- (2- (5- (4- (diphenylamine) phenyl) thiophene-2-yl) vinyl) -1- (4-sulfonamide benzyl) quinoline-1-onium hexafluorophosphate (V) salt, namely fluorescent probe TTQ-GA, is obtained.
3. 3. The method for preparing the golgi targeted aggregation-induced emission ionic probe according to claim 4, wherein the mixed molar ratio of 5- (4- (diphenylamine) phenyl) thiophene-2-carbaldehyde (TTC) to 4-methyl-1- (4-sulfamidobenzyl) quinoline-1-onium hexafluorophosphate (V) (Q-SBN) is 1:1-1:10.
4. 4. The method for preparing the golgi targeted aggregation-induced emission ionic probe according to claim 4, wherein the reaction time is 4-48 hours.
5. 5. The method for preparing the golgi targeted aggregation-induced emission ionic probe according to claim 4, wherein the feeding ratio of dichloromethane/methanol as an eluent is 1:1-100:1.

Description

Targeted Golgi AIE ionic probe, preparation method and application Technical Field The invention relates to the field of organic fluorescent probe molecules, in particular to an ionic probe for targeting aggregation-induced emission of a Golgi apparatus, a preparation method and application thereof. . Background The golgi apparatus, which serves as a core secretory organelle of eukaryotic cells, is responsible for post-translational modification of proteins, sorting trafficking, regulation of lipid synthesis, and lysosome production. The unique polar membrane vesicle structure has a key regulation and control effect on cell homeostasis, and the structural abnormality or dysfunction of the golgi body has been confirmed to be closely related to a variety of major diseases, including neurodegenerative diseases (alzheimer's disease, parkinson's disease), tumor metastasis, metabolic syndrome and the like. Since golgi apparatus is highly dependent on the redox balance of the membrane system, its multi-layered membrane capsule structure is abnormally sensitive to oxidative stress factors such as Reactive Oxygen Species (ROS). Therefore, the method has important significance for analyzing the pathological mechanism and developing the targeted treatment strategy aiming at the precise dynamic tracing and space-time resolution imaging technology of the Golgi apparatus. In the field of development of Golgi apparatus specific fluorescent probes, the existing probes generally face the problems of poor permeability, insufficient polar retention capacity and the like of a membrane system, so that long-time living imaging has obvious limitations. The traditional probe has a light emitting mechanism based on a planar conjugated structure, aggregation fluorescence quenching (ACQ) is easy to occur in a compact film structure of a Golgi apparatus, and imaging resolution and stability are seriously affected. In recent years, probes with aggregation-induced emission (AIE) properties have shown unique advantages in maintaining dynamic tracking of the golgi membrane system due to their abnormal nature of "hydrophobic aggregation-enhanced emission". The AIE probe not only can realize long-term imaging with ultra-high signal-to-noise ratio, but also can synchronously carry out drug delivery and curative effect monitoring through functional modification. In recent years, development of light-activated aggregation-induced emission materials has been significantly advanced, but the synthesis path of the light-activated aggregation-induced emission materials still faces process bottlenecks such as lengthy multi-step organic reactions and difficult directional functional modification. The existing system has two general technical defects that firstly, the photophysical response mode is single, multi-dimensional in-situ monitoring of subcellular organelle microenvironment parameters (such as pH, viscosity and active oxygen cluster gradient) is difficult to realize synchronously, and secondly, the diagnosis and treatment function is split, and the light-emitting unit and the treatment module lack of cooperative design of a molecular layer. More notably, the current oxidative stress research is mostly dependent on exogenous stimulus factors (such as exogenous introduced H2O2, doxorubicin or peroxisome activators), and the intervention means is easy to cause imbalance of an intracellular redox network, so that subcellular organelle specific stress signals are covered by system noise, and accurate analysis of dynamic changes of key organelle microenvironments such as golgi is severely restricted. Disclosure of Invention Aiming at the defects and defects of the prior art, the invention provides an ionic probe for targeting aggregation-induced emission of a golgi apparatus, a preparation method and application thereof, wherein a benzenesulfonamide group of the probe selectively combines with a golgi apparatus protein cyclooxygenase 2 (COX-2) inhibitor SC-558 to realize the targeting of the golgi apparatus, a hydrophobic triphenylamine part of the probe and a hydrophilic quinoline cation part of the probe enable the probe to have amphipathy, the probe does not emit fluorescence in an aqueous solution, and can emit strong fluorescence when the molecular movement is limited and excited, thereby realizing the washing-free marking of the golgi apparatus, and the probe generates a large amount of ROS under the excitation of light, thereby promoting the local lipid peroxidation of the golgi apparatus and the apoptosis of cancer cells. The invention relates to an ionic probe for targeting aggregation-induced emission of a Golgi apparatus, which is characterized in that the ionic near-infrared fluorescent probe has a chemical structural formula as follows: 。 The specific molecular structure benzenesulfonamide group of the probe has selective combination on a golgi protein cyclooxygenase 2 (COX-2) inhibitor SC-558 to realize golgi targeting, the fluoresce