CN108815529B - Spherical conjugated polymer nano particle functionalized by quaternary ammonium salt and antibacterial application thereof - Google Patents

Spherical conjugated polymer nano particle functionalized by quaternary ammonium salt and antibacterial application thereof Download PDF

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CN108815529B
CN108815529B CN201810699457.4A CN201810699457A CN108815529B CN 108815529 B CN108815529 B CN 108815529B CN 201810699457 A CN201810699457 A CN 201810699457A CN 108815529 B CN108815529 B CN 108815529B
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唐艳丽
王恋琪
张梓颀
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Abstract

The invention discloses a quaternary ammonium salt functionalized spherical conjugated polymer nano particle and antibacterial application thereof, wherein the nano particle takes a hydrophobic conjugated polymer as an inner core, quaternary ammonium salt functional group molecules form a shell on the surface through hydrophobic effect, and the spherical conjugated polymer nano particle is finally obtained, wherein the structural formula of the hydrophobic conjugated polymer is shown in the specification
Figure DDA0001713928490000011
The structural formula of the quaternary ammonium salt functional group molecule is
Figure DDA0001713928490000012
The conjugated polymer nanoparticles can realize broad-spectrum efficient antibacterial without light source or other energy under the condition of keeping out of the sun, and the antibacterial rate of the conjugated polymer nanoparticles is far higher than that of functional groups with the same concentrationThe antibacterial rate of the molecule is not easy to generate drug resistance, and a new idea is provided for the development of future antibacterial nano materials.

Description

Spherical conjugated polymer nano particle functionalized by quaternary ammonium salt and antibacterial application thereof
Technical Field
The invention belongs to the technical field of nano particle antibiosis, and particularly relates to a novel conjugated polymer nano particle and application of the nano particle as an antibacterial material.
Background
With the emergence of drug-resistant bacteria in recent years, it has become important to develop novel antibacterial agents and antibacterial methods having high antibacterial performance without being affected by bacterial resistance. The nano antibacterial material greatly improves the antibacterial activity due to the advantages of small size, large specific surface area and the like. Compared with the traditional antibacterial agent, the nano antibacterial material has the advantages of difficult generation of drug resistance, lasting antibacterial property, broad-spectrum antibacterial property and the like. Although the common antibacterial nano materials have good antibacterial performance, most of the common antibacterial nano materials need photocatalysis and have biological toxicity to mammalian cells, especially heavy metal nano particles, so the application of the common antibacterial nano materials in biomedicine is limited.
Conjugated Polymer Nanoparticles (CPNs) are novel nano materials which are rapidly developed in recent years, and nanoparticles prepared based on conjugated polymers generally have the advantages of bright fluorescence, good colloidal stability, high biocompatibility, low cytotoxicity and the like, so that the nanoparticles are widely applied to aspects of biological imaging, diagnosis, treatment and the like.
Disclosure of Invention
The invention aims to provide a novel quaternary ammonium salt functionalized spherical conjugated polymer nanoparticle and application of the conjugated polymer nanoparticle in the aspect of antibiosis.
The quaternary ammonium salt functionalized spherical conjugated polymer nanoparticles used for solving the technical problems are nanospheres which are formed by hydrophobic conjugated polymers and quaternary ammonium salt functional group molecules through hydrophobic effect and take the hydrophobic conjugated polymers as cores and the quaternary ammonium salt functional group molecules as shells.
The structural formula of the hydrophobic conjugated polymer is shown as follows:
Figure BDA0001713928470000011
wherein R is selected from C1～C20Alkyl, aryl, heteroaryl, and heteroaryl,
Figure BDA0001713928470000012
M is an integer of 1 to 19, X1Represents Br or I, n represents polymerization degree; the number average molecular weight of the hydrophobic conjugated polymer is 10000-50000, and the preparation method comprises the following steps: adding the compound of the formula I, the compound of the formula II and palladium acetate into a mixed solvent of dimethylformamide and triethylamine according to the molar ratio of 1:1:0.036, reacting for 4 hours at 100 ℃, and separating and purifying a product to obtain the hydrophobic conjugated polymer.
Figure BDA0001713928470000021
The structural formula of the quaternary ammonium salt functional group molecule is shown as follows:
Figure BDA0001713928470000022
wherein X represents Cl or Br and p is 3, 4, 6, 8, 9, 10, 12, 14, 16 or 18.
The preparation method of the conjugated polymer nano particle comprises the following steps: the nano-particle is prepared by uniformly dispersing a hydrophobic conjugated polymer and quaternary ammonium salt functional group molecules in tetrahydrofuran under the condition of ultrasonic ice bath, quickly injecting the obtained solution into deionized water, continuing ultrasonic treatment for 10-20 minutes, and then removing tetrahydrofuran and partial deionized water.
In the preparation method, the molar ratio of the hydrophobic conjugated polymer to the quaternary ammonium salt functional group molecules is 1: 1-5, and the volume ratio of the added tetrahydrofuran to the added deionized water is 1: 1-3.
The conjugated polymer nano particle is used as an antibacterial material, and the bacteria are escherichia coli, staphylococcus aureus and the like.
The conjugated polymer nano particle takes a hydrophobic conjugated polymer as an inner core, and a cationic surfactant with a quaternary ammonium group forms a shell on the surface through hydrophobic action, so that the spherical conjugated polymer nano particle is finally obtained. The invention controls the particle size of the generated nano particles by controlling the molar ratio of the hydrophobic conjugated polymer to the quaternary ammonium salt functional group molecules, the volume ratio of the water phase to the tetrahydrofuran and the concentration of the hydrophobic conjugated polymer and the quaternary ammonium salt functional group molecules in a system. The nano particles can realize broad-spectrum efficient antibacterial without light sources or other energy under the condition of keeping out of the sun, the antibacterial rate of the nano particles is far higher than that of quaternary ammonium salt functional group molecules with the same concentration, the nano particles are not easy to generate drug resistance, and a new thought is provided for the development of future antibacterial nano materials.
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FIG. 1 is a transmission electron micrograph of conjugated polymer nanoparticles prepared in example 1.
FIG. 2 shows the bactericidal activity of the conjugated polymer nanoparticles prepared in example 1 against E.coli under dark conditions.
FIG. 3 shows the bactericidal activity of conjugated polymer nanoparticles prepared in example 1 against Staphylococcus aureus under light-shielding conditions.
Detailed Description
The invention will be further described in detail with reference to the following figures and examples, but the scope of the invention is not limited to these examples.
Example 1
Under the condition of ultrasonic ice bath, 0.1mg of hydrophobic conjugated polymer c-1 and 0.1mg of hexadecyl trimethyl ammonium bromide are added into 5mL of tetrahydrofuran, the mixture is uniformly dispersed by ultrasonic, the obtained mixed solution is quickly poured into a flask containing 15mL of secondary water, the mixture is uniformly mixed by gentle shaking, and the ultrasonic treatment is continued for 15 minutes. And after the ultrasonic treatment is finished, the solution is returned to the room temperature, tetrahydrofuran in the mixed solution is removed under the room temperature condition by using a needle head to blow nitrogen, part of deionized water is removed under the heating condition, and the solution is concentrated to 5mL to obtain the conjugated polymer nano particles. As can be seen from FIG. 1, the particle size of the obtained nanoparticles was about 50 nm.
The synthetic route and the synthetic method of the hydrophobic conjugated polymer c-1 are as follows:
Figure BDA0001713928470000031
1. a50 mL round bottom flask was charged with 7.2mL (50mmol) of 1-bromohexane, 0.33g (1mmol) of tetrabutylammonium bromide, and 20mL of 50% by mass KOH aqueous solution, and after deoxygenating for 30 minutes, the reaction mixture was warmed to 75 ℃ and 1.62g (5mmol) of 2, 7-dibromofluorene was added, and reflux continued at 75 ℃ for 15 minutes. And extracting, drying and concentrating the reaction mixed solution, and then carrying out column chromatography separation to obtain the compound a-1.
2. 738.5mg (1.5mmol) of compound a-1 and 10mL of toluene are added to a 25mL round-bottom flask, 1.43mL (4.5mmol) of tributylvinyltin, 2mg (0.0095mmol) of 2, 6-di-tert-butylphenol and 47.4mg (0.0675mmol) of bis (triphenylphosphine) palladium chloride are sequentially added after deoxygenation for 30 minutes, the reaction mixture is refluxed at 100 ℃ for 7 hours, cooled to room temperature, 10mL of a 10% by mass aqueous solution of KF is added and stirred overnight, and after removal of solid residues, extraction, drying and concentration, column chromatography separation is performed to obtain compound b-1.
3. 96.7mg (0.25mmol) of the compound b-1, 1.67mL of dimethylformamide and 0.83mL of triethylamine are added into a 25mL round-bottom flask, oxygen is removed for 30min, 73.5mg (0.25mmol) of 4, 7-dibromo-2, 1, 3-benzothiadiazole, 2mg (0.009mmol) of palladium acetate and 15mg (0.049mmol) of tri-p-tolyl phosphate are sequentially added, and the reaction mixture is refluxed at 100 ℃ for 4 hours, extracted, dried, concentrated and centrifugally precipitated to obtain the hydrophobic conjugated polymer c-1. M of the hydrophobic conjugated polymer c-1 detected by gel permeation chromatographyn＝44810，Mw＝47827，PDI＝1.07。
Example 2
Under the condition of ultrasonic ice bath, 0.1mg of hydrophobic conjugated polymer c-2 and 0.1mg of hexadecyl trimethyl ammonium bromide are added into 5mL of tetrahydrofuran, the mixture is uniformly dispersed by ultrasonic, the obtained mixed solution is quickly poured into a flask containing 15mL of secondary water, the mixture is uniformly mixed by gentle shaking, and the ultrasonic treatment is continued for 15 minutes. And after the ultrasonic treatment is finished, the solution is returned to the room temperature, tetrahydrofuran in the mixed solution is removed under the room temperature condition by using a needle head to blow nitrogen, part of deionized water is removed under the heating condition, and the solution is concentrated to 5mL to obtain the conjugated polymer nano particles.
The synthetic route and the synthetic method of the hydrophobic conjugated polymer c-2 are as follows:
Figure BDA0001713928470000051
in the synthesis method, only the 1-bromohexane in example 1 needs to be replaced by the equimolar 1, 6-dibromohexane, and the other steps are the same as the synthesis method of c-1, so that the hydrophobic conjugated polymer c-2 is obtained. M of the hydrophobic conjugated polymer c-2 by gel permeation chromatography detectionn＝13958，Mw＝15078，PDI＝1.08。
Example 3
Under the condition of ultrasonic ice bath, 0.1mg of hydrophobic conjugated polymer e-3 and 0.1mg of hexadecyl trimethyl ammonium bromide are added into 5mL of tetrahydrofuran, the mixture is uniformly dispersed by ultrasonic, the obtained mixed solution is quickly poured into a flask containing 15mL of secondary water, the mixture is uniformly mixed by gentle shaking, and the ultrasonic treatment is continued for 15 minutes. And after the ultrasonic treatment is finished, the solution is returned to the room temperature, tetrahydrofuran in the mixed solution is removed under the room temperature condition by using a needle head to blow nitrogen, part of deionized water is removed under the heating condition, and the solution is concentrated to 5mL to obtain the conjugated polymer nano particles.
The synthetic route and the synthetic method of the hydrophobic conjugated polymer e-3 are as follows:
Figure BDA0001713928470000061
1. a100 mL round-bottomed flask was charged with 6mL (75mmol) of triethylene glycol monomethyl ether, 10mL of CH2Cl2And 2.07mL (15mmol) of triethylamine was added thereto while cooling on ice, and 1.42g (7.5mmol) of p-toluenesulfonyl chloride was dissolved in 10mL of CH2Cl2Dropwise adding the mixture into the solution, reacting at normal temperature overnight, extracting, drying, concentrating, and performing column chromatography separation to obtain a compound a-3.
2. Adding 30mL of anhydrous acetone, 1.27g (4mmol) of the compound a-3 and 1.4g (16mmol) of LiBr into a 100mL round-bottom flask, heating the mixed solution to 85 ℃, refluxing for reaction overnight, cooling to room temperature, extracting, drying, concentrating, and separating by column chromatography to obtain the compound b-3.
3. 0.4g (1.76mmol) of compound b-3, 0.23g (0.71mmol) of 2, 7-dibromofluorene, 0.02g (0.06mmol) of tetrabutylammonium bromide, 2mL of DMSO and 0.56mL of 50% KOH aqueous solution are added into a 50mL round bottom flask, the temperature is raised to 100 ℃, the reaction is refluxed overnight, then the mixture is cooled to room temperature, and the compound c-3 is obtained after extraction, drying and concentration and column chromatography separation.
4. 924.6mg (1.5mmol) of compound c-3 and 10mL of toluene are added to a 25mL round-bottom flask, 1.43mL (4.5mmol) of tributylvinyltin, 2mg (0.0095mmol) of 2, 6-di-tert-butylphenol and 47.4mg (0.0675mmol) of bis (triphenylphosphine) palladium chloride are sequentially added after deoxygenation for 30 minutes, the reaction mixture is refluxed at 100 ℃ for 7 hours, cooled to room temperature, 10mL of a 10% by mass aqueous solution of KF is added and stirred overnight, and after removal of solid residues, extraction, drying and concentration, column chromatography separation is performed to obtain compound d-3.
5. 127.7mg (0.25mmol) of compound d-3, 1.67mL of dimethylformamide and 0.83mL of triethylamine were added to a 25mL round-bottomed flask, and after deoxygenation for 30min, 73.5mg (0.25mmol) of 4, 7-dibromo-2, 1, 3-benzothiadiazole, 2mg (0.009mmol) of palladium acetate and 15mg (0.049mmol) of tri-p-tolyl phosphate were sequentially added to the flask, and the reaction mixture was refluxed at 100 ℃ for 4 hours, extracted, dried, concentrated and then centrifuged to precipitate to obtain conjugated polymer e-3. M of the hydrophobic conjugated polymer e-3 detected by gel permeation chromatographyn＝16589，Mw＝23420，PDI＝1.41。
Example 4
Example 1 application of the conjugated Polymer nanoparticles prepared in example 1 as antibacterial Material
Staphylococcus aureus and Escherichia coli stored at-80 ℃ were streaked onto TSB agar plates and LB agar plates, respectively, and incubated overnight in a water-proof incubator at 37 ℃ for first-generation activation. Single colonies on agar plates were picked and placed in 25mL medium and incubated in a shaker at 37 ℃ for about 12 hours to their logarithmic growth phase. The bacteria in the logarithmic growth phase were collected by centrifugation, washed twice with 0.9% NaCl solution, the supernatant was removed, and finally 0.9% NaCl solution was added to obtain a bacterial suspension.
Conjugated polymer nanoparticles (final concentrations of 0, 0.2, 0.5, 0.8, 1.0, 1.5, 2.0. mu.g/mL, respectively) and bacterial suspension (final concentration of 2X 10)7cfu/mL) were mixed and incubated in a dark environment for 30 minutes and 60 minutes, respectively. After the incubation was completed, the cells were stained with a SYTO 9/PI mixed dye and the viability of the cells was measured by flow cytometry. The sampling amount is 100000 signals, the signal collection selects FL1(530 + -15 nm) channel to collect green fluorescence signal, and FL2(585 + -20 nm) channel to collect red fluorescence signal. At the same time, a blank control experiment and an antibacterial experiment of Cetyl Trimethyl Ammonium Bromide (CTAB) with the same concentration were carried out for each treatment. The results of the bacteriostatic ratio are shown in fig. 2 and fig. 3.
As can be seen from FIG. 2, the antibacterial effect of the Escherichia coli and the conjugated polymer nanoparticles is almost consistent after incubation for 30 minutes and 60 minutes in the dark, which indicates that the nanoparticles complete the process of binding to the bacteria and destroying the bacterial membrane in 30 minutes, and the antibacterial activity is positively correlated with the concentration of the nanoparticles, and when the concentration of the nanoparticles is 0.8. mu.g/mL, the mortality rate of the bacteria reaches 91%.
As can be seen from FIG. 3, the antibacterial process of the conjugated polymer nanoparticles to Staphylococcus aureus can be completed within 30 minutes, the change trend of the antibacterial activity is basically consistent with that of the antibacterial activity of Escherichia coli, and the antibacterial rate can reach 96% due to the fact that the gram-positive bacteria have tougher cell walls than the gram-negative bacteria in structure and 1.0 μ g/mL of nanoparticles are incubated for 30 minutes in a dark condition. And from the figure we can also see that 0 to 1.0 μ g/mL CTAB has almost no antibacterial activity, and the antibacterial rate of the nanoparticles at this concentration can exceed 90%, which indicates that the antibacterial performance of the conjugated polymer nanoparticles is not derived from CTAB but is realized by the combined action of forming nanoparticles with the conjugated polymer. The experimental results show that the conjugated polymer nanoparticles have efficient broad-spectrum antibacterial activity under the condition of keeping out of the sun.

Claims (5)

1. A spherical conjugated polymer nanoparticle functionalized by quaternary ammonium salt is characterized in that: the nano-particle is a nano-sphere which is formed by hydrophobic conjugated polymer and quaternary ammonium salt functional group molecules through hydrophobic effect and takes the hydrophobic conjugated polymer as an inner core and the quaternary ammonium salt functional group molecules as an outer shell;
the structural formula of the hydrophobic conjugated polymer is shown as follows:
Figure DEST_PATH_IMAGE002
wherein R is selected from C1～C20Alkyl, aryl, heteroaryl, and heteroaryl,
Figure DEST_PATH_IMAGE004
、
Figure DEST_PATH_IMAGE006
、
Figure DEST_PATH_IMAGE008
M is an integer of 1 to 19, X1Represents Br or I, n represents polymerization degree; the number average molecular weight of the hydrophobic conjugated polymer is 10000-50000;
the structural formula of the quaternary ammonium salt functional group molecule is shown as follows:
Figure DEST_PATH_IMAGE010
wherein X represents Cl or Br, p is 3, 4, 6, 8, 9, 10, 12, 14, 16 or 18;
the nano-particle is prepared by uniformly dispersing a hydrophobic conjugated polymer and quaternary ammonium salt functional group molecules in tetrahydrofuran under the condition of ultrasonic ice bath, quickly injecting the obtained solution into deionized water, continuing ultrasonic treatment for 10-20 minutes, and then removing tetrahydrofuran and partial deionized water.
2. The quaternary ammonium salt functionalized spherical conjugated polymer nanoparticles according to claim 1, wherein: the molar ratio of the hydrophobic conjugated polymer to the quaternary ammonium salt functional group molecules is 1: 1-5.
3. The quaternary ammonium salt functionalized spherical conjugated polymer nanoparticles according to claim 1, wherein: the volume ratio of the added tetrahydrofuran to the deionized water is 1: 1-3.
4. Use of the quaternary ammonium salt functionalized spherical conjugated polymer nanoparticles of claim 1 as an antibacterial material.
5. The use of quaternary ammonium salt functionalized spherical conjugated polymer nanoparticles according to claim 4 as antibacterial material, characterized in that: the bacteria are escherichia coli or staphylococcus aureus.
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Publication number Priority date Publication date Assignee Title
CN103053517A (en) * 2013-01-18 2013-04-24 陕西师范大学 Synthesis method and application of fluorescence DNA-polyphenylene acetylene hydrogel
CN105001193A (en) * 2015-07-15 2015-10-28 陕西师范大学 Cationic water-soluble oligothiophene acetylene compound, and preparation method and application thereof
CN105963697A (en) * 2016-05-31 2016-09-28 陕西师范大学 Composite antibacterial agent based on fluorescent conjugated polymer and upconversion nanometer material and using method thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103053517A (en) * 2013-01-18 2013-04-24 陕西师范大学 Synthesis method and application of fluorescence DNA-polyphenylene acetylene hydrogel
CN105001193A (en) * 2015-07-15 2015-10-28 陕西师范大学 Cationic water-soluble oligothiophene acetylene compound, and preparation method and application thereof
CN105963697A (en) * 2016-05-31 2016-09-28 陕西师范大学 Composite antibacterial agent based on fluorescent conjugated polymer and upconversion nanometer material and using method thereof

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
"A Molecular Brush Approach to Enhance Quantum Yield and Suppress Nonspecifi c Interactions of Conjugated Polyelectrolyte for Targeted Far-Red/Near-Infrared Fluorescence Cell Imaging";Kan-Yi Pu etal;《Adv. Funct. Mater》;20101231(第20期);第2771页图1 *
"Efficient bacteria capture and inactivation by cetyltrimethylammonium bromide modified magnetic nanoparticles";Yinjia Jin etal;《Colloids and Surfaces B: Biointerfaces》;20151201;第136卷;第660页左栏第1-3段，右栏1段；第661页右栏1-2段，第664页右栏2段 *
Conjugated Polymer Based Nanoparticles as Dual-ModalProbes for Targeted In Vivo Fluorescence and Magnetic Resonance Imaging;Kai Li et al;《Adv. Funct. Mater》;20121231(第22期);第3107–3115页 *
Conjugated-Polyelectrolyte-Based Polyprodrug: Targeted and Image-Guided Photodynamic and Chemotherapy with On-Demand Drug Release upon Irradiation with a Single Light Source;Youyong Yuan etal;《Cancer Nanotechnology》;20141231(第53期);第7163 –7168页 *
Tuning Antibacterial Activity of Cyclodextrin-Attached Cationic Ammonium Surfactants by a Supramolecular Approach;Chengcheng Zhou;《ACS Appl. Mater. Interfaces》;20171231(第9期);第31657-31666页 *

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