阅读说明：本技术 一种含芘-吡啶基团的共轭聚合物及其合成方法与应用 (conjugated polymer containing pyrene-pyridine group and synthetic method and application thereof ) 是由 黄红梅 赵雅倩 肖毅 张艳然 何晓晓 张友玉 于 2019-09-11 设计创作，主要内容包括：一种含芘-吡啶基团的共轭聚合物及其合成方法与应用,所述共轭聚合物如式I或II所示；所述合成方法采用以芘衍生物与2,6-二(乙炔基)吡啶为单体,通过Sonogashira缩聚反应合成得到本发明共轭聚合物；本发明制备纳米粒子的方法：将共轭聚合物溶于易挥发溶剂中,得到浓度为60~125ppm的共轭聚合物溶液；向表面活性剂溶液中加入所述共轭聚合物溶液,超声至溶液澄清,过滤,即得。本发明共轭聚合物属于低聚合物,尺寸小,可制备粒径小于10nm的纳米粒子；所得的纳米粒子的平均粒径小于10nm,将其应用于金属离子、有机小分子和细胞成像领域,有助于提高检测方法的检测限和灵敏度。(A conjugated polymer containing pyrene-pyridine groups is shown as a formula I or II, and is synthesized by taking pyrene derivatives and 2, 6-di (ethynyl) pyridine as monomers through a Sonogashira condensation polymerization reaction to obtain the conjugated polymer.)

1. A conjugated polymer containing pyrene-pyridine group is characterized in that the chemical structural formula is shown as formula I, wherein,

n is 2-20; preferably, n is 3 to 10, more preferably, n is 4,

2. A synthesis method of a conjugated polymer containing pyrene-pyridine groups is characterized in that pyrene derivatives and 2, 6-di (ethynyl) pyridine are used as monomers, and the conjugated polymer containing pyrene-pyridine groups is synthesized through Sonogashira condensation polymerization, wherein the pyrene derivatives are shown in a formula III or IV, wherein, X ═ Cl or-Br,

3. The method for synthesizing the pyrene-pyridine group-containing conjugated polymer according to claim 2, wherein the catalyst for the Sonogashira polycondensation reaction is CuI and Pd (PPh)₃)₄(ii) a Preferably, the temperature of the Sonogashira polycondensation reaction is 35-60 ℃, and preferably 40 ℃; preferably, the amount of CuI and Pd (PPh)₃)₄The amount of the substance(s) does not exceed 10% of the amount of the pyrene derivative substance; preferably, the mass ratio of the pyrene derivative to the 2, 6-di (ethynyl) pyridine is 1: 1-1.2.

4. The method for synthesizing the pyrene-pyridine group-containing conjugated polymer according to claim 2 or 3, comprising the steps of:

(1) weighing pyrene derivative, 2, 6-di (ethynyl) pyridine, CuI and Pd (PPh) according to the proportion₃)₄then adding a mixed solution of toluene and diisopropylamine to form a reaction solution, heating the reaction solution to 40-60 ℃ in an inert gas atmosphere, reacting for 12-48 h, cooling to room temperature, filtering, washing a filter cake, collecting filtrate and washing liquid, and concentrating to obtain a crude product;

(2) Adding CHCl needed for dissolving the crude product into the crude product obtained in the step (1)₃And then adding methanol to separate out a precipitate, filtering, washing a filter cake, combining filtrate and washing liquor, and concentrating to obtain the pyrene-pyridine group-containing conjugated polymer.

5. the method for synthesizing the pyrene-pyridine group-containing conjugated polymer according to claim 4, wherein in the step (1), the volume ratio of the toluene to the diisopropylamine is 4: 1; preferably, the concentration of the pyrene derivative in the reaction solution is 0.02-0.03 mol/L, and preferably 0.025 mol/L; preferably, the washing liquid is CHCl in sequence₃And THF; preferably, in step (2), the crude CHCl required for dissolution is used₃the mass ratio of the volume of (a) to the crude product is 1.5-3.125 mL/mg; preferably, the mass ratio of the volume of the methanol to the crude product is 1.5-3.125 mL/mg.

6. A method for preparing nano particles by using a conjugated polymer containing pyrene-pyridine groups is characterized by comprising the following steps:

S1: dissolving the conjugated polymer of claim 1 in a volatile solvent to obtain a conjugated polymer solution with a concentration of 60-125 ppm;

S2: and adding the conjugated polymer solution into a surfactant solution, performing ultrasonic treatment until the solution is clear, and filtering to remove macromolecular substances to obtain the nano particles.

7. The method for preparing nanoparticles from pyrene-pyridine group-containing conjugated polymer according to claim 6, wherein the surfactant is selected from one of PEG-COOH, PEG-b-PPG-b-PEG, DSPE-PEG-Mal and DSPE-mPEG2000, wherein PEG-COOH is a surfactant of formula V, PEG-b-PPG-b-PEG is a surfactant of formula VI, DSPE-PEG-Mal is a surfactant of formula VII, DSPE-mPEG2000 is a surfactant of formula VIII,

8. the method for preparing the nano particles by adopting the pyrene-pyridine group-containing conjugated polymer according to the claim 6 or 7, wherein the mass ratio of the surfactant to the conjugated polymer is 20-30: 1; more preferably, the mass ratio of the surfactant to the conjugated polymer is 25: 1; preferably, the concentration of the surfactant solution is 0.001 g/mL-0.02 g/mL; more preferably, the concentration of the surfactant solution is 0.001 g/mL.

9. The method for preparing nanoparticles by using the pyrene-pyridine group-containing conjugated polymer according to any one of claims 6 to 8, wherein the volatile solvent is one or more selected from dichloromethane, chloroform, tetrahydrofuran and methanol.

10. Nanoparticles prepared from a pyrene-pyridine group-containing conjugated polymer, characterized in that they are prepared by the method of any one of claims 6 to 9.

Technical Field

The invention relates to a conjugated polymer material and the application field thereof, in particular to a synthetic method of a conjugated polymer containing pyrene-pyridine groups, and a method for preparing nano particles by adopting the conjugated polymer and the application thereof.

background

In recent years, conjugated polymers have received much attention as a new type of chemical and biological sensing material. Conjugated Polymers (CP) have macromolecules with a p-conjugated backbone with high quantum yields. It is widely used in the fields of light emitting diodes, solar cells, plastic lasers, biochemical sensing, and the like (chem.soc.rev.2010,39,2411). Conjugated Polymer Nanoparticles (CPNs) have been the focus of research in biochemical sensors due to their many unique attributes such as high light absorption quality, high brightness, good photostability, good compatibility and tunable spectral properties (adv. funct. mater.2019,29, 1806818).

currently, there are many studies on the use of CPNs for cellular imaging, cancer, etc. disease detection in the context of complex organisms (Adv Polym sci.2015, 12, 324). It has been reported that reducing the size of CPNs can reduce non-specific interactions and thereby increase detection limits and sensitivity (jadv. mater.,2012,24, 3498-3504).

In 2004, Masuhara and co-workers prepared nanoparticles with (3- [2- (N-dodecylcarbamoyloxy) ethyl ] thiophene-2, 5-diyl) (P3DDUT) in the size range of 40-400nm and studied its spectral properties (Chem Phys Chem.,2004,5, 1609-1615). Mecking and colleagues synthesized various fluorescent conjugated polymer nanoparticles with a size of about 30nm by Acyclic Diene Metathesis (ADMET) polycondensation, Glaser coupling reaction, and Sonogashira coupling reaction in aqueous miniemulsion (J Am Chem Soc. 2009131, 14267-14273).

It has been reported that nanoparticles with a size of 20 to 200nm can be non-specifically internalized into cells, significantly compromising the selectivity and sensitivity of the detection process (chem.

Disclosure of Invention

the invention aims to solve the technical problem of overcoming the defects in the prior art and provides a conjugated polymer containing pyrene-pyridine groups, and a synthetic method and application thereof. The conjugated polymer belongs to an oligomer, has small size and is beneficial to preparing nano particles with small particle size.

the invention further aims to solve the technical problems that: provides a method for preparing nano particles by adopting a conjugated polymer containing pyrene-pyridine groups, and the particle size of the nano particles prepared by the method is less than 10 nm. .

the technical scheme adopted by the invention for solving the technical problems is as follows:

A conjugated polymer containing pyrene-pyridine groups has a chemical structural formula shown as a formula I, wherein n is 2-20; preferably, n is 3 to 10; more preferably, n is 4,

The synthesis method of the pyrene-pyridine group-containing conjugated polymer comprises the steps of taking a pyrene derivative and 2, 6-di (ethynyl) pyridine as monomers, and carrying out Sonogashira condensation polymerization reaction to synthesize the pyrene-pyridine group-containing conjugated polymer, wherein the pyrene derivative is shown as a formula III or IV, X is-Cl or-Br,

Preferably, the catalyst for Sonogashira polycondensation reaction is CuI and Pd (PPh)₃)₄。

Preferably, the temperature of the Sonogashira polycondensation reaction is 35-60 ℃, and preferably 40 ℃.

Preferably, the amount of CuI and Pd (PPh)₃)₄The amount of the substance(s) is not more than 10% of the amount of the pyrene derivative substance. The higher the levels of tetrakis (triphenylphosphine) palladium and CuI, the faster the reaction, but if the levels are too high, it will be detrimental to the formation of a polymer of the desired uniform degree of polymerization.

preferably, the mass ratio of the pyrene derivative to the 2, 6-di (ethynyl) pyridine is 1.0: 1.0-1.2.

Preferably, the synthesis method comprises the following steps:

(1) Weighing pyrene derivative, 2, 6-di (ethynyl) pyridine, CuI and Pd (PPh) according to the proportion₃)₄Then, adding a mixed solution of toluene and diisopropylamine to form a reaction solution, heating the reaction solution to 40-60 ℃ in an inert gas atmosphere, reacting for 12-48 h, cooling to room temperature, filtering, washing a filter cake, collecting filtrate and washing liquid, and concentrating to obtain a crude product;

(2) Adding CHCl needed for dissolving the crude product into the crude product obtained in the step (1)₃And then adding methanol to separate out a precipitate, filtering, washing a filter cake, combining filtrate and washing liquor, and concentrating to obtain the pyrene-pyridine group-containing conjugated polymer.

Preferably, in step (1), the volume ratio of toluene to diisopropylamine is 4: 1.

Preferably, in the step (1), the concentration of the pyrene derivative in the reaction solution is 0.01 to 0.03mol/L, and preferably 0.025 mol/L.

preferably, in step (1), the washing liquid is CHCl₃And THF.

Preferably, in step (2), the crude CHCl required for dissolution is used₃the mass ratio of the volume of (a) to the crude product is 1.5-3.125 mL/mg.

preferably, in the step (2), the mass ratio of the volume of the methanol to the crude product is 1.5-3.125 mL/mg.

Preferably, the Pd (PPh)₃)₄The synthesis method comprises the following steps: PdCl₂mixing triphenylphosphine and dimethyl sulfoxide in a mass ratio of 1: 5-10: 50-150 (more preferably 1: 6-8: 80-120), under the protection of nitrogen,Stirring and heating to 140-160 ℃, keeping the temperature for reaction for 12-18 min, then changing the color of the solution from yellow to red, dripping hydrazine hydrate at the speed of 0.5-1.5 mL/min according to the mass ratio of the hydrazine hydrate to the dimethyl sulfoxide of 1: 60-100 (more preferably 1: 70-90), standing, cooling, filtering, pumping and washing filter residues with ethanol for more than or equal to 4 times, and washing with diethyl ether for more than or equal to 2 times to obtain the Pd (PPh)₃)₄。

Preferably, the synthesis method of the 2, 6-di (ethynyl) pyridine comprises the following steps:

(a) Weighing 26-dibromopyridine and Pd (PPh) according to the substance ratio of 1:0.05:0.05 in turn₃)₄And CuI, adding a mixed solution of toluene and diisopropylamine with a volume ratio of 4:1, then adding 2 times of equivalent of trimethylsilylacetylene, reacting for 12h, filtering, concentrating, and separating by a column to obtain an intermediate

(b) Dissolving the intermediate obtained in the step (a) into a mixed solution of tetrahydrofuran and methanol with the volume ratio of 1:1, and adding 7 times of equivalent of K₂CO₃Stirring for 12 hours, filtering, concentrating the filtrate, and separating by a column to obtain the 2, 6-di (ethynyl) pyridine.

the technical scheme adopted for further solving the technical problems is as follows:

a method for preparing nanoparticles by using the conjugated polymer containing pyrene-pyridine groups comprises the following steps:

S1: dissolving the conjugated polymer containing pyrene-pyridine groups in a volatile solvent to obtain a conjugated polymer solution with the concentration of 60-125 ppm;

S2: adding a surfactant into deionized water, performing ultrasonic treatment for 10min to form a surfactant solution, adding the conjugated polymer solution into the surfactant solution, performing ultrasonic treatment until the solution is clear, and filtering to remove macromolecular substances to obtain the nanoparticles.

The concentration of the conjugated polymer solution is too low, so that the conjugated polymer is difficult to agglomerate to form nano particles, and the yield is low; the high concentration makes the agglomeration of the conjugated polymer easier to agglomerate, and makes the particle size of the formed nano particles larger. The ultrasonic treatment to clarify the solution means that the volatile solvent is completely volatilized by ultrasonic treatment, so that the aqueous solution of the nano particles is formed.

preferably, the surfactant is selected from one or more of PEG-COOH, PEG-b-PPG-b-PEG, DSPE-PEG-Mal and DSPE-mPEG2000, wherein PEG-COOH is a surfactant shown in formula V, PEG-b-PPG-b-PEG is a surfactant shown in formula VI, DSPE-PEG-Mal is a surfactant shown in formula VII, and DSPE-mPEG2000 is a surfactant shown in formula VIII.

preferably, the mass ratio of the surfactant to the conjugated polymer is 20-30: 1, and more preferably, the mass ratio of the surfactant to the conjugated polymer is 25: 1.

Preferably, the concentration of the surfactant solution is 0.001 g/mL-0.02 g/mL; more preferably, the concentration of the surfactant solution is 0.001 g/mL.

Preferably, the volatile solvent is selected from one or more of dichloromethane, chloroform, tetrahydrofuran and methanol; more preferably, the volatile solvent is dichloromethane.

preferably, the filtration is across a 0.22 μm water film.

preferably, the ultrasonic time is 0.5-24 h; more preferably, the ultrasonic time is 12-20 h.

The nano particles prepared by the method also belong to the protection scope of the invention.

The invention has the beneficial effects that:

(1) The conjugated polymer belongs to an oligomer, has small polymerization degree and small molecular weight, is easy to form nanoparticles with small particle size, contains pyrene and pyridine groups, is easy to agglomerate through the pi-pi action of aromatic rings, avoids the problem that the agglomeration is difficult when the concentration of the conjugated polymer is too low, and is easier to form nanoparticles; further, the pyrene group of the conjugated polymer has strong fluorescence emission, so that detection and imaging are facilitated; the lone pair electrons on the pyridine group have strong electron affinity and electron transmission performance, and are easy to coordinate with metal ions to generate fluorescence quenching in the detection process, so that the detection of the metal ions is facilitated;

(2) According to the synthetic method of the conjugated polymer, the oligomeric conjugated polymer is successfully synthesized through Sonogashira polycondensation reaction, and although the Sonogashira polycondensation reaction is common coupling reaction, the conjugated polymer is successfully synthesized through the limitation of raw materials of pyrene derivatives and 2, 6-di (ethynyl) pyridine and the limitation of conditions such as reaction temperature, reaction time and the like;

(3) the method for preparing the nano particles successfully prepares the nano particles with the particle size of less than 10nm by regulating the concentration of a conjugated polymer solution and combining the characteristic of small polymerization degree of the conjugated polymer of the invention and adopting a microemulsion method, and the application of the method in the fields of detecting metal particles, organic micromolecules and cell imaging is favorable for obviously reducing the detection limit of the detection method and improving the sensitivity of the detection method;

(4) the nano particles prepared by the method have excellent water dispersibility, the polymer is easy to dissolve in organic solvents such as tetrahydrofuran, dichloromethane, trichloromethane, methanol and the like, and the application range is wide; the size of the nano particles can be regulated and controlled by changing the concentration of the polymer in dichloromethane, so that the method is suitable for different detection methods; meanwhile, the method is simple and easy to implement and low in investment cost.

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of a conjugated polymer synthesized in example 1 of the present invention;

FIG. 2 is an enlarged view of a portion of FIG. 1;

FIG. 3 is a TEM image of nanoparticles prepared by example 3 using the conjugated polymer synthesized in example 1;

FIG. 4 is a graph showing the size distribution of nanoparticles prepared by using the conjugated polymer synthesized in example 1 in example 3;

FIG. 5 is a graph showing an ultraviolet absorption spectrum and a fluorescence spectrum of the nanoparticle solution prepared in example 3;

FIG. 6 is a TEM image of a synthetic polymeric nanoparticle of comparative example 1;

FIG. 7 is a width dimension distribution diagram of the synthesized polymer P1 nanorods of comparative example 1;

FIG. 8 is a length dimension distribution diagram of the synthesized polymer P1 nanorods of comparative example 1.

Detailed Description

the present invention will be further described with reference to the following examples and the accompanying drawings.

The nitrogen used in the embodiment of the invention is high-purity nitrogen with the purity of more than or equal to 99.999 percent; the argon gas is high-purity argon gas with the purity of more than or equal to 99.999 percent. The chemical reagents used in the examples of the present invention, unless otherwise specified, are commercially available in a conventional manner.

Reference example 1: synthesis of tetrakis (triphenylphosphine) palladium

PdCl₂Mixing triphenylphosphine and dimethyl sulfoxide according to the mass ratio of 1: 5-10: 50-150 (more preferably 1: 6-8: 80-120), stirring and heating to 140-160 ℃ under the protection of nitrogen, keeping the temperature for reaction for 12-18 min, enabling the color of the solution to turn red from yellow, stopping the reaction at the speed of 0.5-1.5 mL/min by using hydrazine hydrate and dimethyl sulfoxide according to the mass ratio of 1: 60-100 (more preferably 1: 70-90), standing, cooling, filtering, performing suction washing on filter residues with ethanol for more than or equal to 4 times, and performing dropwise addition washing with diethyl ether for more than or equal to 2 times.

Reference example 2: synthesis of 2, 6-di (ethynyl) pyridine

A50 mL three-necked flask was charged with 0.95g (4mmol) of 2, 6-dibromopyridine and Pd (PPh)₃)₄0.232g (0.2mmol) and CuI 38.1mg (0.2mmol), 15mL of toluene are added under nitrogen: diisopropylamine was mixed with 4:1 solvent, and 1.1mL of trimethylsilylacetylene was slowly added through a syringe. After 12 hours reaction at room temperature (25 ℃), the filtrate was black, and insoluble matter was removed, the filtrate was concentrated to obtain the product as a white solid in petroleum ether: and (4) taking dichloromethane as a developing agent, and passing through a column. The obtained filtrate was spin-dried to obtain 600mg of an intermediate.

The product was dissolved in 18mL tetrahydrofuran: to a 1:1 methanol solvent was added 3.54g K₂CO₃After stirring at room temperature (25 ℃) for 12 hours, the insoluble material was filtered off, the filtrate was concentrated, and the crude product was purified by distillation with petroleum ether: dichloromethane 1:1 as developing solvent, and separating through column to obtain 300mg of product.