CN109517107B - Thermo-sensitive poly (propionyl aminoethyl acrylate-co-benzoyl aminoethyl acrylate) and preparation method thereof - Google Patents
Thermo-sensitive poly (propionyl aminoethyl acrylate-co-benzoyl aminoethyl acrylate) and preparation method thereof Download PDFInfo
- Publication number
- CN109517107B CN109517107B CN201811432331.7A CN201811432331A CN109517107B CN 109517107 B CN109517107 B CN 109517107B CN 201811432331 A CN201811432331 A CN 201811432331A CN 109517107 B CN109517107 B CN 109517107B
- Authority
- CN
- China
- Prior art keywords
- acrylate
- oxazoline
- temperature
- reaction
- acrylic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/34—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate
- C08F220/36—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate containing oxygen in addition to the carboxy oxygen, e.g. 2-N-morpholinoethyl (meth)acrylate or 2-isocyanatoethyl (meth)acrylate
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Medicinal Preparation (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Abstract
The invention provides temperature-sensitive poly (propionyl aminoethyl acrylate-co-benzoyl aminoethyl acrylate) and a preparation method thereof, wherein the chemical structural formula is shown as a formula (I), wherein x = 0.10-0.28, and y = 0.72-0.90; the lowest critical solution temperature is 22.6-39.2 ℃; the material is prepared by taking 2-phenyl-2-oxazoline, 2-ethyl-2-oxazoline and acrylic acid with a specific feed ratio as raw materials, performing ring-opening reaction, and performing free radical copolymerization reaction. The polymer disclosed by the invention not only has excellent temperature-sensitive characteristics, but also has good biocompatibility, is simple in preparation method, mild in condition, rapid in reaction and simple and convenient to operate, can be used in application fields with high requirements on the biocompatibility of temperature-sensitive materials, such as drug controlled release, bioseparation, immunoassay and the like, and has important research and development values.
Description
Technical Field
The invention relates to a polymer and a preparation method thereof, in particular to thermosensitive poly (propionyl aminoethyl acrylate-co-benzoyl aminoethyl acrylate) and a preparation method thereof.
Background
The temperature sensitive polymer is a macromolecule with reversible response characteristic to the temperature change of the external environment, is an important intelligent material, and is widely applied to the biomedical fields of drug controlled release, bioseparation, enzyme immobilization, immunoassay and the like. One of the most important physical parameters of a temperature-sensitive polymer is the Lowest Critical Solution Temperature (LCST) or the highest critical solution temperature (UCST), i.e. the temperature at which an aqueous polymer solution reversibly changes its physical or chemical properties with a change in temperature.
The premise that the polymer material has temperature-sensitive characteristics is that a macromolecular chain contains a hydrophilic group and a hydrophobic group which are relatively balanced, and water molecules can generate hydrogen bond action (hydrophilicity) with the macromolecular chain along with temperature change and are continuously enhanced or weakened. At present, common temperature-sensitive polymers are mainly classified into polyamides, polyethers, polyesters and the like.
Polyacrylic acid is a common water-soluble polymer, and has acid-base sensitivity due to a large amount of carboxyl on a molecular chain, but does not have temperature-sensitive characteristics. At present, the design and synthesis of polyacrylic acid-based polymer materials with temperature responsiveness through modification or group modification still face certain challenges.
Disclosure of Invention
One of the objects of the present invention is to provide a thermosensitive poly (propionylaminoethyl acrylate-co-benzoylaminoethyl acrylate).
The second purpose of the invention is to provide a preparation method of temperature-sensitive poly (propionyl aminoethyl acrylate-co-benzoyl aminoethyl acrylate).
One of the objects of the invention is achieved by:
a thermo-sensitive poly (propionylaminoethyl acrylate-co-benzoylaminoethyl acrylate) having a chemical formula as shown in formula (I):
wherein x = 0.10-0.28, y = 0.72-0.90; the minimum critical solution temperature (LCST) is 22.6-39.2 ℃, and the temperature is close to the room temperature and the body temperature.
Preferably, the molecular weight of the polymer is 2.8-5.1 × 104g/mol, the molecular weight distribution is 1.5-1.9; more preferably, the molecular weight of the polymer is 2.85 to 5.01 x 104g/mol, and the molecular weight distribution is 1.56-1.9.
The second purpose of the invention is realized by the following steps:
a preparation method of thermo-sensitive poly (propionamidoethyl acrylate-co-benzoyl aminoethyl acrylate) comprises the following steps:
(a) ring opening reaction
Carrying out ring-opening reaction on acrylic acid, 2-phenyl-2-oxazoline and 2-ethyl-2-oxazoline to prepare propionylaminoethyl acrylate and benzoylaminoethyl acrylate;
wherein the molar ratio of the 2-ethyl-2-oxazoline, the 2-phenyl-2-oxazoline and the acrylic acid is 0.80-0.95: 0.05-0.20: 1;
(b) after the ring-opening reaction is completed, the propionyl aminoethyl acrylate and the benzoyl aminoethyl acrylate are subjected to free radical copolymerization reaction in the presence of an initiator to prepare the temperature-sensitive poly (propionyl aminoethyl acrylate-co-benzoyl aminoethyl acrylate).
In the step (a), the solvent used for the ring-opening reaction can simultaneously dissolve reaction raw materials (acrylic acid, 2-phenyl-2-oxazoline and 2-ethyl-2-oxazoline), ring-opening reaction products (propionylaminoethyl acrylate and benzoylaminoethyl acrylate) and an initiator; preferably, the solvent may be absolute ethanol, absolute methanol, ethyl acetate, acetone, or the like.
Preferably, in the step (a), the acrylic monomer is dissolved in the solvent, and after the acrylic monomer and the solvent are uniformly mixed, the 2-ethyl-2-oxazoline and the 2-phenyl-2-oxazoline are added to the mixture to perform a ring-opening reaction.
Preferably, in the step (a), the reaction temperature of the ring-opening reaction is room temperature, the reaction time is 5-10 h, and the ring-opening reaction is preferably carried out under stirring.
Preferably, in step (a), the Thin Layer Chromatography (TLC) method is adopted, anhydrous ether is used as a developing agent, and whether the ring-opening reaction of the oxazoline and the acrylic acid monomer is completely performed or not is observed.
In step (b), the initiator for radical copolymerization is known to those skilled in the art, and preferably, the initiator is Azobisisobutyronitrile (AIBN), Benzoyl Peroxide (BPO), azobisisoheptonitrile, or the like.
Preferably, the initiator is Azobisisobutyronitrile (AIBN), and the molar amount of the initiator is 0.5 to 2 percent of that of the acrylic acid monomer.
Preferably, in step (b), the radical copolymerization is carried out under an inert atmosphere; optionally, after the initiator is added into the reaction vessel, the air in the reaction vessel is pumped out and filled with dry high-purity nitrogen, and the process is repeated for 5 times to eliminate oxygen in the air and prevent the polymerization inhibition.
Preferably, in the step (b), the reaction temperature of the free radical copolymerization reaction is 55-80 ℃, and the reaction time is 12-18 h.
Preferably, in the step (b), the reaction mixture obtained after the free radical copolymerization reaction is poured into a dialysis bag to be dialyzed for 24 hours by using distilled water, and freeze-dried to obtain the thermo-sensitive poly (propionyl aminoethyl acrylate-co-benzoyl aminoethyl acrylate).
The potential application of the temperature-sensitive poly (propionyl aminoethyl acrylate-co-benzoyl aminoethyl acrylate) can be applied to the aspects of drug controlled release, bioseparation, immunoassay and the like, in particular to the application field with higher requirements on the biocompatibility and biodegradability of a temperature-sensitive material.
The novel high polymer material with temperature-sensitive characteristic, namely poly (propionamidoethyl acrylate-co-benzamidoethyl acrylate) (PEO-PO), is prepared by synthesizing a novel monomer by using 2-ethyl-2-oxazoline, 2-phenyl-2-oxazoline and acrylic acid with a specific feed ratio as raw materials, and then carrying out free radical copolymerization on the obtained monomer to obtain a target polymer. The preparation method is simple, mild in condition, rapid in reaction and simple and convenient to operate, can be used for rapidly synthesizing the polymer, can effectively regulate and control the hydrophilicity and the hydrophobicity of the polymer material, and promotes the macromolecular chain of the polymer to achieve the relative balance of the hydrophilicity and the hydrophobicity, so that the polymer material can be endowed with good temperature-sensitive characteristics, and more temperature-sensitive polymer materials can be provided for the field of biomedicine.
The Lowest Critical Solution Temperature (LCST) of the novel high polymer material poly (propionyl aminoethyl acrylate-co-benzoyl aminoethyl acrylate) (PEO-PO) is 22.6-39.2 ℃, is close to room temperature and body temperature, has good temperature-sensitive characteristic, has no obvious cytotoxicity, has good biocompatibility, and lays a foundation for the practical application of the material in the field of biomedicine.
The polymer disclosed by the invention not only has excellent temperature-sensitive characteristics, but also has good biocompatibility, has potential application values in the aspects of drug controlled release, bioseparation, immunoassay and the like, and has important research and development values particularly in the application field with higher requirements on the biocompatibility of a temperature-sensitive material.
Drawings
FIG. 1 is an infrared spectrum of poly (propionamidoethyl acrylate-co-benzamidoethyl acrylate) (PEO-PO) prepared in example 1.
FIG. 2 is a hydrogen nuclear magnetic spectrum of poly (propionamidoethyl acrylate-co-benzamidoethyl acrylate) (PEO-PO) prepared in example 1.
FIG. 3 is a UV-visible spectrum of poly (propionamidoethyl acrylate-co-benzamidoethyl acrylate) (PEO-PO) prepared in example 1, i.e., the curve of the transmittance of an aqueous solution of poly (propionamidoethyl acrylate-co-benzamidoethyl acrylate) (PEO-PO) as a function of temperature.
FIG. 4 is the results of toxicity evaluation of poly (propionamidoethyl acrylate-co-benzamidoethyl acrylate) (PEO-PO) prepared in example 1 to HeLa cells.
Detailed Description
The invention is further illustrated by the following examples, which are given by way of illustration only and are not intended to limit the scope of the invention in any way.
Procedures and methods not described in detail in the following examples are conventional methods well known in the art, and the reagents used in the examples are either analytically or chemically pure and are either commercially available or prepared by methods well known to those of ordinary skill in the art. The following examples all achieve the objects of the present invention.
Example 1
(a) Typical small molecule ring opening reactions
In a 25 mL flask containing magnetons, an accurately weighed amount of 0.720 g of acrylic acid monomer and 6 mL of absolute ethanol were added, and stirred for 5min to uniformly mix acrylic acid and ethanol. Accurately weigh 0.891 g of 2-ethyl-2-oxazoline and 0.147 g of 2-phenyl-2-oxazoline and add them to the flask and stir at room temperature for 8 hours to ensure completion of the ring-opening reaction. And (3) observing whether the ring-opening reaction of the oxazoline and the acrylic monomer is completely carried out by adopting a thin-layer chromatography (TLC) method and taking anhydrous ether as a developing agent.
(b) Free radical copolymerization
After the acrylic monomer completely reacts, 0.026g Azodiisobutyronitrile (AIBN) is accurately weighed and added into a reaction bottle, air in the flask is pumped out and dry high-purity nitrogen is filled in, and the reaction is repeated for 5 times to eliminate oxygen in the air and prevent polymerization inhibition. The flask was placed on a heated magnetic stirrer and reacted at 65 ℃ for 18 h. Pouring the reaction mixture into a dialysis bag, dialyzing the reaction mixture with distilled water for 24 hours, and freeze-drying the reaction mixture to obtain poly (propionylaminoethyl acrylate-coBenzoylaminoethylacrylate) (PEO-PO) in a yield of 57.9%.
The reaction equation for this reaction is shown below:
by infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (F)1H-NMR) and ultraviolet-visible spectrum (UV) are used for carrying out structural and performance characterization on the prepared poly (propionamidoethyl acrylate-co-benzoylaminoethyl acrylate) (PEO-PO), the obtained infrared spectrum is shown in figure 1, the hydrogen nuclear magnetic spectrum is shown in figure 2, and the ultraviolet-visible spectrum, namely the change curve of the light transmittance of the aqueous solution of poly (propionamidoethyl acrylate-co-benzoylaminoethyl acrylate) (PEO-PO) along with the temperature is shown in figure 3. In addition, the molecular weight of PEO-PO was 3.64X 104 g/mol, the molecular weight distribution index is 1.86, and the x/y = 15: 85 on the molecular chain of the PEO-PO and the Lowest Critical Solution Temperature (LCST) is 31.5 ℃ through nuclear magnetic data calculation.
Example 2
(a) Typical small molecule ring opening reactions
In a 25 mL flask equipped with magnetons, an accurately weighed amount of 0.720 g of acrylic acid monomer and 6 mL of anhydrous methanol were added, and stirred for 5min to uniformly mix acrylic acid and ethanol. Accurately weighed 0.951 g of 2-ethyl-2-oxazoline and 0.074 g of 2-phenyl-2-oxazoline, were added to the flask and stirred at room temperature for 10 hours to ensure completion of the ring-opening reaction. And (3) observing whether the ring-opening reaction of the oxazoline and the acrylic monomer is completely carried out by adopting a thin-layer chromatography (TLC) method and taking anhydrous ether as a developing agent.
(b) Free radical copolymerization
After the acrylic monomer completely reacts, 0.034g of Azobisisobutyronitrile (AIBN) is accurately weighed and added into a reaction bottle, air in the flask is pumped out and dry high-purity nitrogen is filled, and the reaction is repeated for 5 times to eliminate oxygen in the air and prevent polymerization inhibition. The flask was placed on a heated magnetic stirrer and reacted at 60 ℃ for 12 h. Pouring the reaction mixture into a dialysis bag, dialyzing the reaction mixture with distilled water for 24 hours, and freeze-drying the reaction mixture to obtain poly (propionylaminoethyl acrylate-coBenzoylaminoethylacrylate) (PEO-PO) in a yield of 65.3%. PEO-PO has a molecular weight of 2.85X 104g/mol, molecular weight distribution index of 1.71, x/y = 10: 90 on PEO-PO molecular chain, and Lowest Critical Solution Temperature (LCST) of 39.2 ℃.
Example 3
(a) Typical small molecule ring opening reactions
In a 25 mL flask containing magnetons, an accurately weighed amount of 0.720 g of acrylic acid monomer and 6 mL of anhydrous ethyl acetate were added, and stirred for 6 min to uniformly mix acrylic acid and ethanol. Accurately weigh 0.916 g of 2-ethyl-2-oxazoline and 0.110 g of 2-phenyl-2-oxazoline and add them to the flask and stir at room temperature for 6 hours to ensure completion of the ring-opening reaction. And (3) observing whether the ring-opening reaction of the oxazoline and the acrylic monomer is completely carried out by adopting a thin-layer chromatography (TLC) method and taking anhydrous ether as a developing agent.
(b) Free radical copolymerization
After the acrylic monomer completely reacts, 0.020 g of azodiisobutyronitrile is accurately weighed and added into a reaction bottle, air in the flask is pumped out and dry high-purity nitrogen is filled, and the reaction is repeated for 5 times to eliminate oxygen in the air and prevent polymerization inhibition. The flask was placed on a heated magnetic stirrer and reacted at 70 ℃ for 15 h. Pouring the reaction mixture into a dialysis bag, dialyzing the reaction mixture with distilled water for 24 hours, and freeze-drying the reaction mixture to obtain poly (propionylaminoethyl acrylate-coBenzoylaminoethylacrylate) (PEO-PO) in a yield of 68.4%. PEO-PO has a molecular weight of 3.08X 104g/mol, molecular weight distribution index of 1.90, x/y = 12: 88 on PEO-PO molecular chain, and Lowest Critical Solution Temperature (LCST) of 35.9 ℃.
Example 4
(a) Typical small molecule ring opening reactions
In a 25 mL flask containing magnetons, an accurately weighed amount of 0.720 g of acrylic acid monomer and 6 mL of anhydrous acetone were added, and stirred for 5min to uniformly mix acrylic acid and ethanol. Accurately weigh 0.842 g of 2-ethyl-2-oxazoline and 0.221 g of 2-phenyl-2-oxazoline and add them to the flask and stir at room temperature for 5 h to ensure completion of the ring-opening reaction. And (3) observing whether the ring-opening reaction of the oxazoline and the acrylic monomer is completely carried out by adopting a thin-layer chromatography (TLC) method and taking anhydrous ether as a developing agent.
(b) Free radical copolymerization
After the acrylic monomer completely reacts, 0.025 g of Azobisisobutyronitrile (AIBN) is accurately weighed and added into a reaction bottle, the air in the flask is pumped out and is filled with dry high-purity nitrogen, and the reaction is repeated for 5 times to eliminate the oxygen in the air and prevent the polymerization inhibition. The flask was placed on a heated magnetic stirrer and reacted at 55 ℃ for 18 h. Pouring the reaction mixture into a dialysis bag, dialyzing the reaction mixture with distilled water for 24 hours, and freeze-drying the reaction mixture to obtain poly (propionylaminoethyl acrylate-coBenzoylaminoethylacrylate) (PEO-PO) in a yield of 75.1%. PEO-PO has a molecular weight of 5.01X 104g/mol, molecular weight distribution index of 1.69, x/y = 23: 77 on the PEO-PO molecular chain, and minimum critical solution temperature (LCST) of 25.9 ℃.
Example 5
(a) Typical small molecule ring opening reactions
In a 25 mL flask containing magnetons, an accurately weighed amount of 0.720 g of acrylic acid monomer and 6 mL of absolute ethanol were added, and stirred for 5min to uniformly mix acrylic acid and ethanol. Accurately weigh 0.792 g of 2-ethyl-2-oxazoline and 0.294 g of 2-phenyl-2-oxazoline and add them to the flask and stir at room temperature for 6 h to ensure completion of the ring-opening reaction. And (3) observing whether the ring-opening reaction of the oxazoline and the acrylic monomer is completely carried out by adopting a thin-layer chromatography (TLC) method and taking anhydrous ether as a developing agent.
(b) Free radical copolymerization
After the acrylic monomer completely reacts, 0.0289g of azodiisoheptonitrile is accurately weighed and added into a reaction bottle, the air in the flask is pumped out and is filled with dry high-purity nitrogen, and the reaction is repeated for 5 times to eliminate the oxygen in the air and prevent the polymerization inhibition. The flask was placed on a heated magnetic stirrer and reacted at 80 ℃ for 12 h. Pouring the reaction mixture into a dialysis bag, dialyzing the reaction mixture with distilled water for 24 hours, and freeze-drying the reaction mixture to obtain poly (propionylaminoethyl acrylate-coBenzoylaminoethylacrylate) (PEO-PO) in 73.2% yield. PEO-PO has a molecular weight of 3.56X 104g/mol, molecular weight distribution index of 1.54, x/y = 28: 72 on the PEO-PO molecular chain, and minimum critical solution temperature (LCST) of 22.6 ℃.
Comparative example 1
In a 25 mL flask containing magnetons, an accurately weighed amount of 0.720 g of acrylic acid monomer and 6 mL of absolute ethanol were added, and stirred for 5min to uniformly mix acrylic acid and ethanol. Accurately weigh 0.990 g of 2-ethyl-2-oxazoline and add it to the flask and stir at room temperature for 8 hours to ensure completion of the ring opening reaction.
After the acrylic monomer completely reacts, 0.026g Azodiisobutyronitrile (AIBN) is accurately weighed and added into a reaction bottle, air in the flask is pumped out and dry high-purity nitrogen is filled in, and the reaction is repeated for 5 times to eliminate oxygen in the air and prevent polymerization inhibition. The flask was placed on a heated magnetic stirrer and reacted at 65 ℃ for 18 h. The reaction mixture was poured into a dialysis bag and dialyzed against distilled water for 24 hours, followed by freeze-drying to obtain polyacrylamide ethyl acrylate (PEO) at a yield of 83.7%.
Comparative example 2
(a) Typical small molecule ring opening reactions
In a 25 mL flask containing magnetons, an accurately weighed amount of 0.720 g of acrylic acid monomer and 6 mL of absolute ethanol were added, and stirred for 5min to uniformly mix acrylic acid and ethanol. Accurately weigh 0.743 g of 2-ethyl-2-oxazoline and 0.368 g of 2-phenyl-2-oxazoline, add them to the flask and stir at room temperature for 10 h to ensure completion of the ring-opening reaction. And (3) observing whether the ring-opening reaction of the oxazoline and the acrylic monomer is completely carried out by adopting a thin-layer chromatography (TLC) method and taking anhydrous ether as a developing agent.
(b) Free radical copolymerization
After the acrylic monomer completely reacts, 0.030 g of Azobisisobutyronitrile (AIBN) is accurately weighed and added into a reaction bottle, air in the flask is pumped out and dry high-purity nitrogen is filled, and the reaction is repeated for 5 times to eliminate oxygen in the air and prevent polymerization inhibition. The flask was placed on a heated magnetic stirrer and reacted at 65 ℃ for 12 h. Pouring the reaction mixture into a dialysis bag, dialyzing the reaction mixture with distilled water for 24 hours, and freeze-drying the reaction mixture to obtain poly (propionylaminoethyl acrylate-coBenzoylaminoethylacrylate) (PEO-PO) in a yield of 71.2%.
Comparative example 3
(a) Typical small molecule ring opening reactions
In a 25 mL flask containing magnetons, an accurately weighed amount of 0.720 g of acrylic acid monomer and 6 mL of anhydrous ethyl acetate were added, and stirred for 5min to uniformly mix acrylic acid and ethanol. Accurately weigh 0.594 g of 2-ethyl-2-oxazoline and 0.588 g of 2-phenyl-2-oxazoline and add them to the flask and stir at room temperature for 5 hours to ensure completion of the ring-opening reaction. And (3) observing whether the ring-opening reaction of the oxazoline and the acrylic monomer is completely carried out by adopting a thin-layer chromatography (TLC) method and taking anhydrous ether as a developing agent.
(b) Free radical copolymerization
After the acrylic monomer completely reacts, 0.025 g of Azobisisobutyronitrile (AIBN) is accurately weighed and added into a reaction bottle, the air in the flask is pumped out and is filled with dry high-purity nitrogen, and the reaction is repeated for 5 times to eliminate the oxygen in the air and prevent the polymerization inhibition. The flask was placed on a heated magnetic stirrer and reacted at 70 ℃ for 15 h. Pouring the reaction mixture into a dialysis bag, dialyzing the reaction mixture with distilled water for 24 hours, and freeze-drying the reaction mixture to obtain poly (propionylaminoethyl acrylate-coBenzoylaminoethylacrylate) (PEO-PO) in a yield of 65.5%.
Example 6
The temperature-sensitive characteristics of the polymer materials prepared in examples 1 to 5 and comparative examples 1 to 3 were tested, and the test results are shown in table 1 below.
TABLE 1
Note: EO, PO and AA respectively represent 2-ethyl-2-oxazoline, 2-phenyl-2-oxazoline and acrylic monomers.
Example 7
Cytotoxicity evaluation was performed on PEO-PO prepared in example 1 using 3- (4, 5-dimethylthiazole-2) -2, 5-diphenyltetrazolium bromide salt (thiazole blue) Method (MTT). HeLa cells in Dulbecco's modified Eagle's medium, maintained at 37 ℃ in 5% CO2Under air conditions, 10% bovine serum was added. In the laboratory, the 6-well plate concentration was 1.5X 104cells/mL were incubated for one day, and then polymer solutions of varying concentrations (0.2, 1, 5, 25, and 125. mu.g/mL) were added. After 1-3 days of culture, the cells were washed twice with FBS and absorbance was measured at 570nm, and then the survival rate of HeLa was calculated.
The results of toxicity evaluation of the PEO-PO prepared in example 1 to HeLa cells are shown in FIG. 4. As can be seen from the figure, after the HeLa cells are cultured in PEO-PO solutions with the concentrations of 0.2, 1, 5, 25 and 125 mug/mL for 1-3 days, the survival rate of the HeLa cells is higher than 93%. That is, PEO-PO had no significant inhibitory effect, i.e., no significant cytotoxicity, on the growth of HeLa cells. Therefore, the novel temperature-sensitive polymer material can have certain application value in the aspects of drug controlled release, biological separation, immunoassay and the like, and particularly has higher requirements on the biocompatibility and biodegradability of the temperature-sensitive material in the application field.
Claims (9)
1. A thermo-sensitive poly (propionylaminoethyl acrylate-co-benzoylaminoethyl acrylate) is characterized in that the chemical structural formula is shown as the formula (I):
wherein x = 0.10-0.28, y = 0.72-0.90; the lowest critical solution temperature is 22.6-39.2 ℃;
the acrylic acid-2-oxazoline-2-phenyl-oxazoline-2-methyl-acrylic acid is prepared from acrylic acid, 2-phenyl-2-oxazoline and 2-ethyl-2-oxazoline, wherein the molar ratio of the 2-ethyl-2-oxazoline, the 2-phenyl-2-oxazoline and the acrylic acid is 0.80-0.95: 0.05-0.20: 1.
2. The thermo-sensitive poly (propionylaminoethyl acrylate-co-benzoylaminoethyl acrylate) according to claim 1, wherein the molecular weight is 2.8-5.1 x 104g/mol, and the molecular weight distribution is 1.5-1.9.
3. The method for preparing temperature-sensitive poly (propionylaminoethyl acrylate-co-benzoylaminoethyl acrylate) according to claim 1, comprising the steps of:
(a) ring opening reaction
Carrying out ring-opening reaction on acrylic acid, 2-phenyl-2-oxazoline and 2-ethyl-2-oxazoline to prepare propionylaminoethyl acrylate and benzoylaminoethyl acrylate;
wherein the molar ratio of the 2-ethyl-2-oxazoline, the 2-phenyl-2-oxazoline and the acrylic acid is 0.80-0.95: 0.05-0.20: 1;
(b) free radical copolymerization
After the ring-opening reaction is completed, the propionyl aminoethyl acrylate and the benzoyl aminoethyl acrylate are subjected to free radical copolymerization reaction in the presence of an initiator to prepare the temperature-sensitive poly (propionyl aminoethyl acrylate-co-benzoyl aminoethyl acrylate).
4. The method for preparing temperature-sensitive poly (propionylaminoethyl acrylate-co-benzoylaminoethyl acrylate) according to claim 3, wherein the solvent used in the ring-opening reaction in step (a) is absolute ethanol, absolute methanol, ethyl acetate or acetone.
5. The preparation method of the temperature-sensitive poly (propionylaminoethyl acrylate-co-benzoylaminoethyl acrylate) according to claim 3, wherein in the step (a), the reaction temperature of the ring-opening reaction is room temperature, and the reaction time is 5-10 h.
6. The method for preparing temperature-sensitive poly (propionylaminoethyl acrylate-co-benzoylaminoethyl acrylate) according to claim 3, wherein in step (a), the acrylic acid monomer is dissolved in the solvent, and after being uniformly mixed, the 2-ethyl-2-oxazoline and the 2-phenyl-2-oxazoline are added thereto to perform the ring-opening reaction.
7. The method for preparing temperature-sensitive poly (propionylaminoethyl acrylate-co-benzoylaminoethyl acrylate) according to claim 3, wherein in step (b), the initiator of radical copolymerization is azobisisobutyronitrile, benzoyl peroxide or azobisisoheptonitrile, and the molar amount is 0.5-2% of the acrylic acid monomer.
8. The preparation method of the temperature-sensitive poly (propionylaminoethyl acrylate-co-benzoylaminoethyl acrylate) according to claim 3, wherein in the step (b), the free radical copolymerization is performed under an inert atmosphere, the reaction temperature is 60-80 ℃, and the reaction time is 12-18 h.
9. The method for preparing temperature-sensitive poly (propionamidoethyl acrylate-co-benzoyl aminoethyl acrylate) according to claim 3, wherein in the step (b), the reaction mixture obtained after the radical copolymerization is poured into a dialysis bag and dialyzed with distilled water for 24 h, and then freeze-dried to obtain the temperature-sensitive poly (propionamidoethyl acrylate-co-benzoyl aminoethyl acrylate).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811432331.7A CN109517107B (en) | 2018-11-28 | 2018-11-28 | Thermo-sensitive poly (propionyl aminoethyl acrylate-co-benzoyl aminoethyl acrylate) and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811432331.7A CN109517107B (en) | 2018-11-28 | 2018-11-28 | Thermo-sensitive poly (propionyl aminoethyl acrylate-co-benzoyl aminoethyl acrylate) and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109517107A CN109517107A (en) | 2019-03-26 |
| CN109517107B true CN109517107B (en) | 2020-11-24 |
Family
ID=65794478
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811432331.7A Expired - Fee Related CN109517107B (en) | 2018-11-28 | 2018-11-28 | Thermo-sensitive poly (propionyl aminoethyl acrylate-co-benzoyl aminoethyl acrylate) and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109517107B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2560726C1 (en) * | 2014-07-30 | 2015-08-20 | Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Иркутский государственный университет" | Method of obtaining tetrazole-containing paired polymers |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103113595B (en) * | 2012-12-31 | 2014-11-19 | 中科院广州化学有限公司 | Fluorescent block-grafted copolymer with temperature sensitivity and preparation method and application thereof |
| CN103881040A (en) * | 2014-03-10 | 2014-06-25 | 同济大学 | Preparation method of temperature and CO2 double-responsive block copolymer nano micelle |
| CN108484824A (en) * | 2018-04-18 | 2018-09-04 | 苏州科技大学 | A kind of temperature sensing polymer and its preparation method and use |
-
2018
- 2018-11-28 CN CN201811432331.7A patent/CN109517107B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2560726C1 (en) * | 2014-07-30 | 2015-08-20 | Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Иркутский государственный университет" | Method of obtaining tetrazole-containing paired polymers |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109517107A (en) | 2019-03-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wei et al. | Thermosensitive hydrogels synthesized by fast Diels–Alder reaction in water | |
| US11452697B2 (en) | Intracellular delivery vehicle | |
| Virtanen et al. | Aggregation in aqueous poly (N-isopropylacrylamide)-block-poly (ethylene oxide) solutions studied by fluorescence spectroscopy and light scattering | |
| Jiménez et al. | Hydrogen bond-directed formation of stiff polymer films using naturally occurring polyphenols | |
| Bostan et al. | Controlled release of 5-aminosalicylicacid from chitosan based pH and temperature sensitive hydrogels | |
| US20030120028A1 (en) | Thermal responsive, water-soluble polymers | |
| Zhang et al. | Poly (N‐isopropylacrylamide)‐based comb‐type grafted hydrogel with rapid response to blood glucose concentration change at physiological temperature | |
| Komatsu et al. | Facile preparation of degradable thermoresponsive polymers as biomaterials: Thermoresponsive polymers prepared by radical polymerization degrade to water-soluble oligomers | |
| CN108948413A (en) | The method that wave polymerization prepares thymopeptide-5 molecule imprinting hydrogel | |
| CN109517107B (en) | Thermo-sensitive poly (propionyl aminoethyl acrylate-co-benzoyl aminoethyl acrylate) and preparation method thereof | |
| CN109467639B (en) | Thermo-sensitive poly (acetamido ethyl acrylate-co-benzoyl amino ethyl acrylate) and preparation method thereof | |
| Wei et al. | Preparation of thermosensitive hydrogels by means of tandem physical and chemical crosslinking | |
| CN109943001B (en) | Self-assembly of azophenyl micromolecule photo-control temperature-sensitive macromolecule PNIPAm in ionic liquid | |
| CN102304194A (en) | Thermal sensitivity adjustable biocompatible core-shell structured polymer nanogel and preparation method thereof | |
| Leemans et al. | Synthesis of new amphiphilic block copolymers. Block copolymer of sulfonated glycidyl methacrylate and alkyl methacrylate | |
| CN110129030B (en) | Preparation and application of block polymer nano-material fluorescent probe with stimulus responsiveness | |
| CN104926976B (en) | Glycosaminoglycan similar to object and its synthetic method and its in vitro embryonic stem cell proliferation and orientation Neural Differentiation in application process | |
| Elshaarani et al. | Glucose-responsive nanostructured hydrogels with enhanced elastic and swelling properties | |
| CN107177585B (en) | Enzyme immobilization carrier and preparation method thereof | |
| CN109988780A (en) | High-performance genophore and its application based on glycidyl methacrylate | |
| CN106750383B (en) | Polyethylene glycol hydrogel material and preparation method thereof | |
| Xu et al. | Fabrication of a novel temperature sensitive poly (N-isopropyl-3-butenamide) hydrogel | |
| CN111393562B (en) | Temperature-responsive polyhydroxyethyl methacrylate and preparation method thereof | |
| CN102942651A (en) | Galactose-base temperature-sensitive microgel and preparation method thereof | |
| CN113493545B (en) | Composition and method for producing linear polymer by light-operated RAFT polymerization in living cells |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20201124 Termination date: 20211128 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |