阅读说明：本技术 一种基于聚集诱导发光效应的荧光聚合物及其制备方法和应用 (Fluorescent polymer based on aggregation-induced emission effect and preparation method and application thereof ) 是由 顾星桂 周良宇 王冠 杨万泰 于 2019-12-09 设计创作，主要内容包括：本发明公开了一种粒径可控且便于修饰的基于聚集诱导发光效应的多功能荧光聚合物及其制备方法和应用。所述荧光聚合物含有式(I)所示的结构式单元：<Image he="465" wi="548" file="DDA0002308776440000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>其中,n＝10～10000,R为具有聚集诱导发光功能的结构基团。将AIE可聚合单元、马来酸酐、苯乙烯、以及任选的交联剂在引发剂存在下进行沉淀聚合反应得到所述荧光聚合物。所述荧光聚合物可应用在免疫调控、细胞标记、材料抗菌、粗糙度检测中。(The invention discloses a multifunctional fluorescent polymer with controllable particle size and convenient modification based on aggregation-induced emission effect, and a preparation method and application thereof. The fluorescent polymer contains a structural formula unit shown as a formula (I): wherein n is 10-10000, and R is a structural group with aggregation-induced emission function. And carrying out precipitation polymerization reaction on the AIE polymerizable unit, maleic anhydride, styrene and an optional cross-linking agent in the presence of an initiator to obtain the fluorescent polymer. The fluorescent polymer can be applied to immune regulation, cell marking, material antibiosis and roughness detection.)

1. A fluorescent polymer based on aggregation-induced emission effects, characterized in that the fluorescent polymer comprises a unit of formula (I):

wherein n is 10-10000, and R is a structural group with aggregation-induced emission function.

2. The fluorescent polymer of claim 1, wherein:

n is 100 to 10000, and R is a group containing a tetraphenylethylene structure.

3. The fluorescent polymer of claim 2, wherein:

r is selected from the group comprising any of the following structures:

4. a method of preparing a fluorescent polymer according to any one of claims 1 to 3, comprising the steps of:

and carrying out precipitation polymerization reaction on the AIE polymerizable unit, maleic anhydride, styrene and an optional cross-linking agent in the presence of an initiator to obtain the fluorescent polymer.

5. The method of claim 4, comprising the steps of:

adding an AIE polymerizable unit, maleic anhydride, styrene and an optional cross-linking agent into a solvent, then adding an initiator, and carrying out polymerization reaction under an anaerobic condition, wherein the polymerization temperature is 40-100 ℃, and the polymerization reaction time is 10 min-5 h.

6. A method of preparing a fluorescent polymer according to claim 4 or 5, characterized in that:

the molar ratio of the styrene to the maleic anhydride is 0.01-1.5, and the preferred molar ratio is 0.01-1.0; and/or the presence of a gas in the gas,

the AIE polymerizable unit is 0.1-100% of the molar amount of maleic anhydride, and preferably 0.1-50%; and/or the presence of a gas in the gas,

the dosage of the cross-linking agent is 0-100%, preferably 0-50% of the molar dosage of the maleic anhydride.

7. A method of preparing a fluorescent polymer according to claim 4 or 5, characterized in that:

the AIE polymerizable unit is a molecule with an AIE function and modified by styryl; and/or the presence of a gas in the gas,

the crosslinking agent is selected from at least one of divinylbenzene and NN-methylene bisacrylamide; and/or the presence of a gas in the gas,

the initiator is selected from at least one of azobisisobutyronitrile, azobisisoheptonitrile and dibenzoyl peroxide; and/or the presence of a gas in the gas,

the solvent is at least one selected from ethyl acetate, propyl acetate, butyl acetate, amyl acetate, isoamyl acetate, octyl acetate, ethyl propionate and ethyl butyrate.

8. The method of claim 7, wherein:

the AIE polymerizable unit is selected from at least one of the compounds represented by the following formulas:

9. the fluorescent polymer nanoparticles based on aggregation-induced emission effect obtained by the method for preparing a fluorescent polymer according to any one of claims 4 to 8.

10. Use of the fluorescent polymer according to any one of claims 1 to 3 or the fluorescent polymer obtained by the preparation method according to any one of claims 4 to 8 in immunomodulation, cell labeling, material antibacterium, and roughness detection.

Technical Field

The invention relates to the field of new materials, in particular to a multifunctional fluorescent polymer which has controllable particle size and is convenient to modify and based on aggregation-induced emission effect, and a preparation method and application thereof.

Background

In recent years, polymer fluorescent nanoparticles show more and more important functions and values in the fields of biomedicine, photoelectric devices and the like. Especially in biomedical fields, such as cancer diagnosis and treatment and cell imaging, higher requirements are put on the polymer fluorescent nanoparticles, such as particle size uniformity, surface modifiability, and stability of particle structure. Currently, the method for preparing polymeric fluorescent nanoparticles mainly includes the following four (Li K, liub. polymer-encapsulated organic nanoparticles for fluorescent imaging [ J ]. Chemical Society Reviews,2014,43(18): 6570): self-assembly, emulsion, polymerization, and co-precipitation. The self-assembly method is characterized in that a certain hydrophilic chain segment is modified by oil-soluble fluorescent molecules through a chemical method, and micelles with fluorescent properties are spontaneously formed when the hydrophilic chain segment is dispersed in water. The emulsification method is to dissolve fluorescent molecules in an oil phase and then to drop the fluorescent molecules into an aqueous phase solution containing an emulsifier and a polymer, and to realize the preparation of the nanoparticles by high-speed stirring, however, the method has the defects of easy phase separation in the preparation process, poor particle size uniformity and a large amount of emulsifier. The polymerization method generally refers to an emulsion polymerization method, and specifically, fluorescent nanoparticles are prepared by chemically modifying fluorescent molecules to give double bonds, and then adopting a traditional emulsion polymerization method. The method can prepare the nano particles with uniform and stable particles, but the prepared nano particles contain a large amount of emulsifier on the surface, which limits the wide application of the method. The coprecipitation method is a main approach for preparing the polymer nanoparticles at present, and is specifically implemented by dissolving fluorescent molecules in a water-soluble organic solvent, then dropwise adding the obtained solution into a water-soluble polymer solution, and obtaining the fluorescent nanoparticles under the action of ultrasonic dispersion.

On the other hand, most of fluorescer molecules used in the preparation process of the traditional polymer fluorescent nanoparticles have the phenomenon of Aggregation-induced quenching (Aggregation-induced quenching), and the existence of the phenomenon causes that the content of fluorescent molecules in the prepared fluorescent nanoparticles is very low, so that the polymer fluorescent molecules with higher fluorescent molecule loading rate cannot be obtained. Aggregation Induced Emission (AIE) phenomenon effectively solves the deficiency of ACQ phenomenon, and a material with AIE properties can emit strong fluorescence in a state of molecular Aggregation.

Disclosure of Invention

In order to solve various problems of the current fluorescent nanoparticles and meet the special requirements of future biomedical or industrial production, the invention provides a multifunctional fluorescent polymer with excellent optical properties and based on an aggregation-induced emission effect, and a preparation method and application thereof.

One of the objects of the present invention is to provide a fluorescent polymer based on aggregation-induced emission effect, comprising a structural formula unit represented by formula (I):

wherein n is 10-10000, and R is a structural group with aggregation-induced emission function.

Preferably, n is 100 to 10000, and R is a group containing a tetraphenylethylene structure.

Wherein R is more preferably selected from the group consisting of:

the invention also aims to provide a preparation method of the fluorescent polymer based on the aggregation-induced emission effect, which comprises the following steps: and carrying out precipitation polymerization reaction on the AIE polymerizable unit, maleic anhydride, styrene and an optional cross-linking agent in the presence of an initiator to obtain the fluorescent polymer.

Preferably, the preparation method may comprise the steps of: adding an AIE polymerizable unit, maleic anhydride, styrene and an optional cross-linking agent into a solvent, then adding an initiator, and carrying out polymerization reaction under an anaerobic condition, wherein the polymerization temperature is 40-100 ℃, and the polymerization reaction time is 10 min-5 h.

In a preferred embodiment according to the invention: dissolving an AIE polymerizable unit, maleic anhydride, styrene and an optional cross-linking agent in a required solvent, adding an initiator, introducing nitrogen to remove oxygen for 10min, heating to start a polymerization reaction, stopping the reaction after a certain time, centrifugally washing for several times by using an organic solvent, and putting into a vacuum oven to obtain the clean polymer fluorescent nanoparticles.

The AIE polymerizable unit is a polymerizable unit with AIE properties, specifically refers to a molecule with AIE functions and containing styryl modification, and specific functionality is endowed to the polymer particles.

The AIE polymerizable unit is preferably at least one selected from the group consisting of compounds represented by the following formulae:

wherein, the English name of TPE-V is ((2- (4- ((4-vinylbenzyl) oxy) phenyl) ethene-1,1,2-triyl) tribenzene);

wherein the English name of the TPE-VBC is (Z) -2- ((4- (1,2-diphenyl-2- (4- ((4-diphenyl) oxy) phenyl) (phenyl) methyl) malononitril;

wherein, the English name of TPE-VTP is (Z) -2- ((4- (1,2-diphenyl-2- (4- ((4-diphenyl) oxy) phenyl) (thiophen-2-yl) methyl) malononitrile.

The crosslinking agent is preferably at least one selected from divinylbenzene and NN-methylene bisacrylamide.

The initiator is not particularly limited, and conventional radical polymerization initiators such as azobisisobutyronitrile, azobisisoheptonitrile, and dibenzoyl peroxide may be used.

The solvent in which the polymerization reaction is carried out is preferably one or more mixed solvents of ethyl acetate, propyl acetate, butyl acetate, amyl acetate, isoamyl acetate, octyl acetate, ethyl propionate, ethyl butyrate and the like.

The maleic anhydride and the styrene are used as main monomers for polymerization reaction, and the molar ratio of the styrene to the maleic anhydride is preferably 0.01-1.5, and more preferably 0.01-1.0.

The AIE polymerizable unit is preferably 0.1 to 100 mol%, more preferably 0.1 to 50 mol% of maleic anhydride.

The dosage of the cross-linking agent is preferably 0-100%, more preferably 0-50% of the molar dosage of the maleic anhydride.

The amount of the initiator is the usual amount for radical polymerization, and is preferably 0.1 to 10 percent, more preferably 1 to 10 percent of the molar amount of the maleic anhydride.

In the method, the reaction temperature can be adjusted according to the particle size of the target product, and the preferable adjustable range is 50-80 ℃.

The polymerization reaction time is preferably 10min to 2 h.

The method of the invention can also comprise the steps of washing and drying the obtained fluorescent polymer by using an organic solvent.

Specifically, the polymer particles obtained by the reaction may be washed with an organic solvent, and then dried, wherein the organic solvent is preferably one or more mixed solvents of ethyl acetate, butyl acetate, isoamyl acetate, acetone, ethanol, isopropanol, diethyl ether, acetonitrile, petroleum ether, and the like.

The preparation method overcomes the defects of the preparation method of the polymeric fluorescent nanoparticles in the prior art, such as poor stability, wide particle size distribution, large amount of emulsifier, low effective loading rate of fluorescent molecules, incapability of realizing particle structure design and the like.

The invention also aims to provide fluorescent polymer nanoparticles based on aggregation-induced emission effect, which are obtained by the preparation method of the fluorescent polymer.

The particle size range of the fluorescent polymer nano particles is 50-700 nm, and the particle size distribution range is 0.01-0.15.

The fourth purpose of the invention is to provide the application of the fluorescent polymer or the fluorescent polymer obtained by the preparation method in immune regulation, cell marking, material antibiosis and roughness detection.

The preparation of the fluorescent polymer nano-particle with functionalized surface and controllable particle size can be realized by adjusting and changing the technical means in the invention, and the obtained polymer particle has the following characteristics:

(1) the particles prepared by the method can undergo the growth process from small to large, so that the polymerization reaction can be stopped according to the polymerization reaction time to obtain the polymer fluorescent particles with controllable particle size, wherein the particle size range is 50-700 nm, and the particle size distribution range is 0.01-0.15.

(2) The emulsifier is not additionally added in the polymerization process, and the obtained polymer fluorescent particles have clean surfaces and do not contain any other redundant components.

(3) The polymer structure contains maleic anhydride, and the surface functionalization of the polymer particles can be realized through the reaction of the maleic anhydride and protein or other amino-containing groups.

(4) Different dye loadings, up to 50% dye loading, can be achieved by adjusting the amount of polymerizable units having AIE properties used in the polymerization process. The characteristic is that the traditional fluorescent nanoparticle preparation method cannot be realized.

(5) The polymer structure contains groups with AIE properties, and the change of the functions of the polymer particles, such as sterilization function and the like, can be realized by changing the structure of the luminescent groups.

(6) By utilizing the adjustability of the particle size of the polymer particles, a simple roughness detection reagent can be prepared so as to be applied to devices or large-scale equipment which are inconvenient for precise measurement.

Drawings

FIG. 1: example 1 Infrared Spectroscopy of polymeric fluorescent particles.

FIG. 2: the polymerization time interval was 10min, and the obtained polymer particles were subjected to electron micrograph and particle size distribution.

FIG. 3: fluorescence photograph of natural killer cell labeled by polymer fluorescent particle.

FIG. 4: fluorescent photograph of polymer fluorescent particles for measuring glass roughness.

Detailed Description

While the present invention will be described in detail with reference to the following examples, it should be understood that the following examples are illustrative of the present invention and are not to be construed as limiting the scope of the present invention.

The starting materials used in the embodiments of the present invention are commercially available.