CN-121991147-A - Trehalose aggregation-induced emission fluorescent probe and synthesis method and application thereof

CN121991147ACN 121991147 ACN121991147 ACN 121991147ACN-121991147-A

Abstract

The invention discloses a trehalose aggregation-induced emission fluorescent probe, a synthesis method and application thereof, belonging to the technical field of fluorescent probes, wherein the fluorescent probe with a special structure is synthesized for the first time, alanine and fluorescent molecules are directly coupled, and the trehalose participates in the metabolism of a target object, compared with biological orthogonal marking, the method has the advantages that the direct marking is more convenient, and the trehalose probe is hopeful to research sugar metabolism processes of various bacteria, which is significant to research of life science, different from metabolic marking ways of amino acid participation.

Inventors

ZHANG PENGFEI
WANG YUANYUAN
LUO YUAN
CAI LINTAO

Assignees

深圳先进技术研究院

Dates

Publication Date: 20260508
Application Date: 20231208

Claims (10)

1. A trehalose aggregation-induced emission fluorescent probe is characterized in that the structural formula of the fluorescent probe is shown as follows:
2. The use of the trehalose aggregation-induced emission fluorescent probe according to claim 1 in the preparation of luminescent materials.
3. The use of the trehalose aggregation-induced emission fluorescent probe according to claim 1 as a bio-orthogonal chemical reaction fluorescent label.
4. Use of the trehalose aggregation-induced emission fluorescent probe according to claim 1 for the preparation of a bacterial marker.
5. The use according to claim 4, wherein the bacterial markers allow for real-time localization and tracking of bacteria by fluorescent labeling of the dye.
6. The method for synthesizing a trehalose aggregation-induced emission fluorescent probe as set forth in claim 1, comprising the steps of: 1) Taking 4-halogenated triphenylamine and 5-aldehyde-2-thiophene boric acid pinacol ester as raw materials to carry out Suzuki coupling reaction in the presence of alkaline substances to prepare TPA-S; Wherein, the structural formula of TPA-S is as follows: 2) TPA-S and 4-methylpyridine are used as raw materials to react in the presence of p-toluenesulfonic acid to prepare TPAPy-S Wherein TPAPy-S has the following structural formula: 3) TPAPy-S was reacted with 4-bromo-1-butyne to produce TPAPy-S-Butyne; Wherein TPAPy-S-Butyne has the following structural formula: 4) TPAPy-S-Butyne and 6-azide-trehalose are reacted in the presence of cuprous bromide and trimethylamine to prepare the trehalose aggregation-induced emission fluorescent probe.
7. The method for synthesizing trehalose aggregation-induced emission fluorescent probe according to claim 6, wherein in step 1), 4-halogenated triphenylamine and 5-aldehyde-2-thiopheneboronic acid pinacol ester are dissolved in an organic solvent, an alkaline substance is added, nitrogen or inert gas is introduced, then a catalyst is added for reaction, and the reaction solution is subjected to purification treatment to obtain TPA-S; optionally, the 4-halogenated triphenylamine is 4-bromotriphenylamine or 4-iodotriphenylamine; Optionally, the alkaline substance is potassium carbonate or sodium carbonate; Optionally, the catalyst is a palladium catalyst; optionally, the inert gas is argon; Optionally, the organic solvent is DMF; optionally, the reaction time is 8-16h; optionally, the purification treatment comprises extraction, washing, drying and elution treatments; further alternatively, dichloromethane is used as an extractant in extraction, and ethyl acetate and n-hexane with volume ratio of 1:10-20 are used as eluents in elution treatment; further alternatively, the mass ratio of 4-halogenated triphenylamine to 5-aldehyde-2-thiopheneboronic acid pinacol ester is 2-3:1.
8. The method for synthesizing trehalose aggregation-induced emission fluorescent probe according to claim 6, wherein in step 2), 4-methylpyridine and p-toluenesulfonic acid are added into an organic solvent to be mixed, TPA-S prepared in step 1) is added to react, the reaction liquid is extracted after the reaction is finished, and the organic layer is collected to be purified; Optionally, the organic solvent is DMF; alternatively, the reaction solution is extracted with DCM and saturated saline; optionally, the reaction is reflux reaction, and the reaction time is 8-24 hours; Optionally, after the organic phases are combined, DCM and methanol with the volume ratio of 99:1 are used as eluent for purification; further alternatively, the molar ratio of 4-methylpyridine, p-toluenesulfonic acid to TPA-S is (4.5-7): 0.8-1.5.
9. The method for synthesizing trehalose aggregation-induced emission fluorescent probe according to claim 6, wherein in the step 3), TPAPy-S and 4-bromo-1-butyne are added into an organic solvent, heated for reaction, and purified to obtain TPAPy-S-Butyne; Optionally, the organic solvent is DMF; Optionally, the temperature of the heating reaction is 70-90 ℃, and the heating reaction time is 8-24 hours; optionally, the purification treatment comprises extraction, drying and elution, wherein dichloromethane is used as an extractant during the extraction, and dichloromethane and methanol with the volume ratio of 10:0.5-2 are used as the eluent during the elution; Further alternatively, the molar ratio of TPAPy-S to 4-bromo-1-butyne is 1:4-6.
10. The method for synthesizing the trehalose aggregation-induced emission fluorescent probe according to claim 6, wherein in the step 4), TPAPy-S-Butyne and 6-azide-trehalose are dissolved in an organic solvent to obtain a solution, cuprous bromide is dispersed in triethylamine and added into the solution to react, and the reaction solution is subjected to purification treatment to obtain the trehalose aggregation-induced emission fluorescent probe; Optionally, the organic solvent is DMSO; optionally, the purifying treatment comprises filtering, collecting an organic layer, drying and recrystallizing, wherein the reagent used for the recrystallization is methanol; Alternatively, the molar ratio of TPAPy-S-Butyne, 6-azide-trehalose to cuprous bromide is 1 (0.8-1.2): 0.8-1.2.

Description

Trehalose aggregation-induced emission fluorescent probe and synthesis method and application thereof Technical Field The invention belongs to the technical field of fluorescent probes, relates to a fluorescent probe and a synthesis method and application thereof, and in particular relates to a trehalose aggregation-induced emission fluorescent probe and a synthesis method and application thereof. Background Aggregation-Induced Emission (AIE) is a special phenomenon of luminescence, which refers to the phenomenon that certain molecules (organic molecules or polymers) do not emit light in solution or solid state, but emit intense light in an aggregated form. The aggregation-induced emission phenomenon is generated from the degree of freedom of the spatial environment in which the molecules are located, so that the aggregation-induced emission material has high quantum yield, long lifetime and good optical stability unlike a general emission material. The AIE material has great application potential, especially in the field of biological imaging, and may be used as fluorescent probe for cell or tissue imaging. The bio-orthogonal chemical reaction is a chemical reaction which occurs under physiological conditions, can carry out nondestructive and efficient biological metabolism modification on biomolecules, and is an ideal biological modification technology. After incubation with bio-orthogonal functional group modification on the target (e.g., bacteria, etc.), the active chemical groups are expressed, and then the corresponding bio-orthogonal group modified fluorophores are introduced to achieve efficient fluorescent labeling of the target through covalent bonds. However, the current probe materials capable of realizing fluorescent labeling of targets are relatively deficient, and particularly, the fluorescent labeling probe materials for bacteria are rarely reported, and the bacterial glycometabolism process has important significance for research of life science. Disclosure of Invention The invention aims to provide a trehalose aggregation-induced emission fluorescent probe, a synthesis method and application thereof, wherein the fluorescent probe is a novel functional probe synthesized for the first time, has a novel structure and stable light emitting property, and can effectively mark bacteria. In order to achieve the above purpose, the invention is realized by adopting the following technical scheme: therefore, the invention provides a trehalose aggregation-induced emission fluorescent probe, wherein the structural formula of the fluorescent probe is shown as the formula (I): The invention discloses application of the trehalose aggregation-induced emission fluorescent probe in preparation of luminescent materials. The invention discloses application of the trehalose aggregation-induced emission fluorescent probe as a bio-orthogonal chemical reaction fluorescent marker. The invention discloses application of the trehalose aggregation-induced emission fluorescent probe in preparation of bacterial markers. Preferably, the bacterial markers realize real-time positioning and tracking of bacteria through fluorescent labeling of dyes. Further preferably, the bacteria are pneumobacteria. Still more preferably, the pneumococcal bacteria is klebsiella pneumoniae. The invention also provides a synthesis method of the trehalose aggregation-induced emission fluorescent probe, which comprises the following steps: The method comprises the following steps: 1) Taking 4-halogenated triphenylamine and 5-aldehyde-2-thiophene boric acid pinacol ester as raw materials to carry out Suzuki coupling reaction in the presence of alkaline substances to prepare TPA-S; Wherein, the structural formula of TPA-S is as follows: 2) TPA-S and 4-methylpyridine are used as raw materials to react in the presence of p-toluenesulfonic acid to prepare TPAPy-S Wherein TPAPy-S has the following structural formula: 3) TPAPy-S was reacted with 4-bromo-1-butyne to produce TPAPy-S-Butyne; Wherein TPAPy-S-Butyne has the following structural formula: 4) TPAPy-S-Butyne and 6-azide-trehalose are reacted in the presence of cuprous bromide and trimethylamine to prepare the trehalose aggregation-induced emission fluorescent probe. In certain preferred embodiments, in the step 1), 4-halogenated triphenylamine and 5-aldehyde-2-thiophene boric acid pinacol ester are dissolved in an organic solvent, alkaline substances are added, nitrogen or inert gas is introduced, a catalyst is added for reaction, and the reaction solution is subjected to purification treatment to prepare TPA-S; optionally, the 4-halogenated triphenylamine is 4-bromotriphenylamine or 4-iodotriphenylamine; Optionally, the alkaline substance is potassium carbonate or sodium carbonate; Optionally, the catalyst is a palladium catalyst; optionally, the inert gas is argon; Optionally, the organic solvent is DMF; optionally, the reaction time is 8-16h; optionally, the purification treatment comprise