JP7206612B2 - block copolymer - Google Patents

Description

The present invention relates to a block copolymer that hydrophilizes the surface of a hydrophobic substrate.

Surface hydrophilization of hydrophobic substrates is widely used to impart functions such as antifogging or antifouling properties, antistatic properties, and biocompatibility to surfaces. As a method, plasma treatment, glow discharge treatment, ion etching, etc., a method of generating hydrophilic functional groups on the surface of a hydrophobic polymer base material, a surface active agent coating on the base material surface or a base material A method such as direct kneading into the powder has been used (see, for example, Non-Patent Document 1). However, these methods have problems such as damage to the substrate due to treatment under severe conditions and difficulty in permanently maintaining the hydrophilic surface.

On the other hand, a method of hydrophilizing the surface of a hydrophobic polymer substrate using a photoreactive polymer has also been proposed (see Patent Documents 1, 2 and 3). These methods are efficient and simple, but the reactivity of the photoreactive groups used is low, and uniform hydrophilization cannot be achieved without high-intensity UV irradiation for a relatively long time. In the case of weak resistance, there is a problem that the base material is damaged by ultraviolet irradiation. Furthermore, since a random copolymer is used, cross-linking occurs within or between polymer molecules, resulting in insufficient fixation to the substrate.

Japanese Patent Publication No. 3-505979 JP 2010-59346 A JP 2017-186536 A

Koichi Ochi, Chemistry of Surface Analysis and Modification (Edited by The Adhesion Society of Japan), Nikkan Kogyo Shimbun, 2003, pp.97-145

An object of the present invention is to provide a block copolymer capable of efficiently and simply hydrophilizing a hydrophobic (substrate) surface, and a surface modifier containing the block copolymer.

The inventor of the present invention made earnest studies to solve the above problems. As a result, a block copolymer having a hydrophilic functional group and a highly photoreactive functional group in the side chain was found. can be made hydrophilic, and have completed the present invention.

That is, the present invention is as follows.
[1] A block copolymer having a structure represented by the following general formula (1) and having a number average molecular weight of 1,000 to 1,000,000.

(Wherein, m and n independently represent an integer of 1 or more, Z represents a group represented by —O— or —N(R ₃ )—, A is —O— or —CH ₂ — R ₁ , R ₂ and R ₃ each independently represent a hydrogen atom or a C ₁ -C ₆ hydrocarbon group, R ₄ represents a C ₃ -C ₆ divalent hydrocarbon group , R ₅ represents a fluorine atom, and p represents an integer of 0 to 4.)
[2] The block copolymer according to [1], wherein in the general formula (1), Z and A are groups represented by -O-.
[3] The block copolymer according to [1] or [2], wherein the value of m/(m+n) is from 0.02 to 0.7.

The present invention will be described in detail below.

In the above general formula (1), the C ₁ to C ₆ hydrocarbon groups represented by R ₁ , R ₂ and R ₃ are not particularly limited, but methyl group, ethyl group, propyl group, isopropyl group, cyclopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, cyclobutyl group, pentyl group, neopentyl group, isopentyl group, 1-methylbutyl group, 1-ethylpropyl group, cyclobutylmethyl group, cyclopentyl group, hexyl group, 1-methylpentyl group, 4-methylpentyl group, 1-ethylbutyl group, 2-ethylbutyl group, cyclohexyl group and phenyl group.

The C ₃ to C ₆ divalent hydrocarbon group represented by R ₄ is not particularly limited, but may be -(CH ₂ ) ₃ -, -(CH ₂ ) ₄ -, -(CH ₂ ) ₅ -, - (CH ₂ ) ₆ —, phenylene group and the like are exemplified. If the number of carbon atoms in the divalent hydrocarbon group represented by R ₄ is 2 or less, the glass transition temperature of the block copolymer increases and the molecular mobility of the side chain decreases. is consumed in the cross-linking reaction between the block copolymers rather than in the reaction with the substrate, and the rate of immobilization of the block copolymer on the surface of the substrate decreases. On the other hand, when the carbon number of the divalent hydrocarbon group represented by R ₄ exceeds 6, the azide group concentration in the block copolymer decreases, the cross-linking points decrease, and the block copolymer to the substrate surface It is not preferable because the fixation rate is lowered.

In the block copolymer having the structure represented by the general formula (1), m and n each independently represent an integer of 1 or more. Here, the value of m/(m+n) is preferably 0.02 to 0.7, more preferably 0.05 to 0.5. Within this range, it is excellent in terms of compatibility between the adhesion to the substrate and the effect of inhibiting protein adsorption.

The following general formula (2) included in the general formula (1)

2-methacryloyloxyethylphosphorylcholine represented by is preferred.

The following general formula (3) included in the general formula (1)

(Wherein, R ₂ , R ₄ , R ₅ , A, Z, m and p have the same meanings as defined above). ) propyl methacrylate, 4-(4-azidophenoxy)butyl methacrylate, 5-(4-azidophenoxy)pentyl methacrylate, 6-(4-azidophenoxy)hexyl methacrylate, 3-(4-azido-2,3,5, 6-tetrafluorophenoxy)propyl methacrylate, 4-(4-azidophenyl)butyl methacrylate, 4-(4-azido-2,3,5,6-tetrafluorophenyl)butyl methacrylate, 3-(4-azidophenoxy) Propyl acrylate, 4-(4-azidophenyl)butyl acrylate, 3-(4-azidophenoxy)propyl methacrylamide, 3-(4-azido-2,3,5,6-tetrafluorophenoxy)propyl methacrylamide, 3 Structural units derived from monomers such as -(4-azidophenoxy)propylacrylamide, 4-(4-azidophenyl)butylmethacrylamide, 4-(4-azidophenyl)butylacrylamide are exemplified, From this point of view, structural units derived from 3-(4-azidophenoxy)propyl methacrylate are preferred.

The arrangement of the structural unit represented by general formula (2) and the structural unit represented by general formula (3) is a block structure. By having a block structure, a hydrophilic segment and a hydrophobic segment are introduced into the polymer to exhibit surface activity, and the hydrophobic structural units are selectively adsorbed and immobilized on the surface of the hydrophobic substrate. In the random structure, cross-linking reactions between polymer molecules and within polymer molecules proceed, so that the amount immobilized on the substrate surface is reduced. Also, after immobilization on the substrate, some of the hydrophobic structural units are exposed on the outermost surface, which is not preferable.

The number average molecular weight of the block copolymer having the structure represented by general formula (1) can be selected in the range of 1,000 to 1,000,000. from the viewpoint of 10,000 to 500,000 is preferable. In addition, the polydispersity (Mw/Mn), which is represented by the ratio of the weight average molecular weight (Mw) and the number average molecular weight (Mn), is not particularly limited. It is preferably about 1 to 5 from the viewpoint of the stability of the coating film.

The block copolymer having the structure represented by the general formula (1) may have structural units derived from other monomers within the scope of the effects of the present invention. Structural units derived from other monomers include, but are not limited to, polystyrene, poly(α-methylstyrene), polyvinylbenzyl chloride, polyvinylaniline, sodium polystyrenesulfonate, polyvinylbenzoic acid, polyvinylphosphoric acid, polyvinylpyridine, polydimethyl Styrenic polymers such as aminomethylstyrene and polyvinylbenzyltrimethylammonium chloride; Polyolefins such as polyethylene, polypropylene, polybutadiene, polybutene and polyisoprene; Poly(halogenated olefins) such as polyvinyl chloride, polyvinylidene chloride and polytetrafluoroethylene; Polyvinyl esters such as polyvinyl acetate and polyvinyl propionate, and polyvinyl alcohol which is a saponified product thereof; nitrile-based polymers such as polyacrylonitrile; polymethacrylic acid, polyperfluoroalkyl methacrylate, polyethyl acrylate, polyacrylic acid, polydimethyl Examples include (meth)acryl-based polymers such as aminoethyl acrylate; (meth)acrylamide-based polymers such as polyacrylamide, polymethacrylamide, polydimethylaminopropylacrylamide, and the like.

Examples of the block copolymer of the present invention include block copolymers having a structure represented by the following general formula (4), wherein Z and A are groups represented by —O—.

(In the formula, m, n and _R4 have the same meanings as above.)
A block copolymer having a structure represented by the above general formula (1) can be produced by a conventional method basically based on the technical level of those skilled in the art, including preparation of monomer compounds and polymerization thereof. For example, although the monomers to be used are not particularly limited, 2-methacryloyloxyethylphosphorylcholine, 3-(4-azidophenoxy)propyl methacrylate, 4-(4-azidophenoxy)butyl methacrylate, 5-(4-azidophenoxy) Pentyl methacrylate, 6-(4-azidophenoxy)hexyl methacrylate, 3-(4-azido-2,3,5,6-tetrafluorophenoxy)propyl methacrylate, 4-(4-azidophenyl)butyl methacrylate, 4-( 4-azido-2,3,5,6-tetrafluorophenyl)butyl methacrylate, 3-(4-azidophenoxy)propyl acrylate, 4-(4-azidophenyl)butyl acrylate, 3-(4-azidophenoxy)propyl methacrylamide, 3-(4-azido-2,3,5,6-tetrafluorophenoxy)propylmethacrylamide, 3-(4-azidophenoxy)propylacrylamide, 4-(4-azidophenyl)butylmethacrylamide, 4 A monomer such as -(4-azidophenyl)butylacrylamide is used.

There are no particular restrictions on polymerization, and any of radical polymerization, ionic polymerization, and coordination polymerization may be used as long as it is a living polymerization method, but living radical polymerization is preferably used from the viewpoint of simplicity of operation. Examples of the living radical polymerization method include ATRP (group transfer living radical polymerization) and RAFT (reversible addition-fragmentation chain transfer) polymerization. The ATRP method is a radical polymerization method in which a copper complex consisting of metallic copper or a copper compound and a ligand is used as a catalyst, and an organohalogen compound is used as a polymerization initiator. There is an equilibrium between the "seed" and the "dormant species" in which the radical is capped by a halogen atom, and this equilibrium is greatly biased toward the dormant species, and the radical concentration in the reaction system is kept low. It is a method that suppresses the bimolecular termination reaction that causes a reaction and enables the polymerization of uniform polymer chains. In the presence of an appropriate chain transfer agent, RAFT polymerization proceeds by a reversible chain transfer reaction, and can synthesize a polymer with a high chain end functional group ratio. These living radical polymerization methods are useful for synthesizing block copolymers, but the ATRP method, in which the end of the polymer molecule is a halogen atom that is not bulky, is preferred.

The ATRP polymerization initiator is not particularly limited as long as it is an organic halide, but ethyl 2-bromoisobutyrate, methyl 2-bromopropionate, 2-hydroxyethyl 2-bromoisobutyrate, α? Bromopropionitrile, ethyl 2-chloroisobutyrate, methyl 2-chloropropionate, 2-hydroxyethyl 2-chloroisobutyrate, α-chloropropionitrile and 2-bromoisobutyric acid. These halides may be used alone or in combination.

Among the catalysts for the ATRP method, metallic copper is pure copper such as powdered copper or copper foil. Examples of copper compounds include, but are not limited to, chlorides, bromides, iodides, cyanides, oxides, hydroxides, acetates, sulfates, nitrates, and the like. A copper atom can have a valence of 0, 1, or 2 depending on its electronic state, but the valence is not limited. Polydentate amines used as ligands are exemplified below, but are not limited to these. Ligands are 2,2'-bipyridine, 4,4'-di-(5-nonyl)-2,2'-bipyridine, N-(n-propyl)pyridylmethanimine, N-(n-octyl) pyridylmethanimine, N,N,N',N'',N''-pentamethyldiethylenetriamine, N-propyl-N,N-di(2-pyridylmethyl)amine, hexamethyltris(2-aminoethyl)amine , N,N-bis(2-dimethylaminoethyl)-N,N′-dimethylethylenediamine, 2,5,9,12-tetramethyl-2,5,9,12-tetraazatetradecane, 2,6,9 ,13-tetramethyl-2,6,9,13-tetraazatetradecane, 4,11-dimethyl-1,4,8,11-tetraazabicyclohexadecane, N′,N″-dimethyl-N′,N ''-bis((pyridin-2-yl)methyl)ethane-1,2-diamine, tris[(2-pyridyl)methyl]amine, 2,5,8,12-tetramethyl-2,5,8, 12-tetraazatetradecane, N,N,N',N'',N''',N'''',N''''-heptamethyltetraethylenetetramine, N,N,N',N'- Examples include, but are not limited to, tetrakis(2-pyridylmethyl)ethylenediamine, polyethyleneimine, and the like.

As the polymerization solvent, for example, known radical polymerization solvents such as water, THF, dioxane, acetone, 2-butanone, ethyl acetate, isopropyl acetate, benzene, toluene, DMF, DMSO, methanol, ethanol, isopropanol and mixtures thereof are used. For example, it can be produced by diluting the monomer concentration to 0.01 to 5 mol/L and the polymerization initiator concentration to 1 to 100 mmol/L, and reacting at 0 to 80° C. for 1 to 72 hours. . The polymerization mode is not particularly limited, and examples thereof include bulk polymerization, solution polymerization, suspension polymerization, emulsion polymerization, dispersion polymerization, and precipitation polymerization. Solution polymerization is preferably used because of the simplicity of operation.

The block copolymer of the present invention can be used for various surface modifications such as surface hydrophilization and suppression of protein adsorption. The details of how to use the block copolymer of the present invention will be described later.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a block copolymer that is efficient, simple, excellent in durability, and capable of hydrophilizing the surface of a hydrophobic substrate and suppressing protein adsorption. By using the block copolymer of the present invention, the surface of various hydrophobic polymer substrates can be efficiently and easily hydrophilized.

EXAMPLES The present invention will be described in more detail below based on examples, but the present invention is not limited to these examples.

In the following examples, the physical properties were measured and evaluated by the following methods.
(1) Block copolymer composition ratio It was determined by proton nuclear magnetic resonance spectroscopy ( ¹ H-NMR) spectroscopy using a nuclear magnetic resonance spectrometer (JNM-ECZ400S, manufactured by JEOL Ltd.). Measurement was performed using heavy water as a heavy solvent.
(2) Physical properties of block copolymer Measured by chromatography (GPC). As the GPC apparatus, Tosoh HLC-8320GPC was used, and as the column, Tosoh TSKgel GMH _HR -L was used, the column temperature was set at 40° C., and tetrafluoroethanol was used as the eluent. Using polymethyl methacrylate (PMMA) as a standard sample, molecular weight conversion was performed in terms of PMMA.
(3) Hydrophilicity The effect of immobilizing the block copolymer on the hydrophilicity of the substrate was evaluated by underwater contact angle measurement. This contact angle measurement was evaluated by the water contact angle (180−θ) obtained from the contact angle θ measured using the captive bubble method in which air bubbles are brought into contact with the film surface in water. In the actual measurement, after immersing the measurement sample in pure water overnight, the contact angle was measured by contacting the surface with air bubbles in water at room temperature and normal pressure using a feeler gauge.

Example 1 [Synthesis of block copolymer]
2-Methacryloyloxyethylphosphorylcholine (2.0 g, 6.7 mmol), ethanol 14 mL, copper (II) bromide (3.0 mg, 0.014 mmol), 2,2'-bipyridine (25 .4 mg, 0.16 mmol) and copper (I) bromide (9.6 mg, 0.07 mmol) were added and stirred. After 30 minutes of nitrogen bubbling, ethyl 2? Bromoisobutyrate (9.96 μL, 0.07 mmol) was added and polymerized at 40° C. for 4 hours. The polymer at this stage had Mn=24,000 and Mw/Mn=1.3. After that, a solution of 3-(4-azidophenoxy)propyl methacrylate (0.39 g, 1.47 mmol) dissolved in 6 mL of ethanol was added, and polymerization was continued at 50° C. for 10 hours. The polymerization reaction solution was dropped into 200 mL of THF for reprecipitation, and the precipitated polymer was washed with a THF/methanol 10/1 (volume ratio) solution. After that, it was dissolved in methanol, the copper catalyst was removed by adsorption with silica gel, and dried under reduced pressure to obtain a block copolymer of yellow-brown powder. The obtained block copolymer had Mn=27,000 and Mw/Mn=1.4. The composition ratio was determined from the integral ratio of ¹ H-NMR, and the value of m/(m+n) in the following structural formula (7) was 0.07.
Structural formula of block copolymer (5)

Example 2 [Immobilization on hydrophobic polymer film surface]
By preparing a solution containing 2% by mass of the block copolymer synthesized in Example 1 (solvent: methanol) on a polyvinylidene fluoride (PVDF) film (manufactured by GL Sciences, Smart Bag 2F) cut into 4 cm × 4 cm. After spin-coating the prepared surface modifier at 2000 rpm for 1 minute, UV irradiation (21 mJ/cm ² ) was performed for 2 seconds using a high-pressure mercury lamp (H400P manufactured by Toshiba Lighting & Technology Co., Ltd.). After that, the film substrate was spray-washed with methanol and water to obtain a film substrate with a modified surface.

Example 3 [Evaluation of surface hydrophilicity (wettability) by underwater contact angle measurement]
The contact angle of the film substrate on which the block copolymer prepared in Example 2 was immobilized was 5.4°, indicating high hydrophilicity.

Example 4 [Immobilization on PVDF porous membrane]
A PVDF porous membrane (MV020 manufactured by Microdyne Nadia) was immersed in a solution containing 2% by mass of the block copolymer synthesized in Example 1 (solvent: methanol) for 5 minutes, then at room temperature under a nitrogen atmosphere. and left to dry for 2 hours. Then, UV irradiation (21 mJ/cm ² ) was performed for 2 seconds using a high-pressure mercury lamp (H400P manufactured by Toshiba Lighting & Technology Co., Ltd.). After that, it was washed by irradiating ultrasonic waves for 2 seconds each in ultrapure water and methanol at room temperature. As a result, a surface-modified PVDF porous membrane was obtained.

Example 5 [Confirmation of protein adsorption amount suppression effect]
Insulin (manufactured by Wako Pure Chemical Industries) was used as a sample protein. A 1 cm×1 cm piece of the surface-modified porous membrane prepared in Example 4 was cut. After shaking (80 rpm) for 2 hours in an insulin solution (0.1 mg/mL, diluted with PBS, 5 mL) at room temperature, the cells were washed with PBS. A sample was placed in a φ12×10 5 test tube, 1 mL of BCA reagent manufactured by Thermo Scientific and 1 mL of 4 wt % sodium dodecyl sulfate in PBS were added and heated at 60° C. for 1 hour. After that, the absorbance of the extract at a wavelength of 562 nm was measured using a spectrophotometer (UH5300, manufactured by Hitachi High-Tech Science Co., Ltd.) to quantify the amount of insulin adsorbed to the membrane, which was 0.1 μg/cm ² . rice field. It was shown that the ability of the PEGMA unit to suppress protein adsorption was effectively functioning on the surface-modified porous membrane surface.

Example 6 [Synthesis of block copolymer]
2-methacryloyloxyethylphosphorylcholine (1.1 g, 3.8 mmol), ethanol 8 mL, copper (II) bromide (1.7 mg, 0.008 mmol), 2,2'-bipyridine (14 .4 mg, 0.09 mmol) and copper (I) bromide (5.5 mg, 0.04 mmol) were added and stirred. After nitrogen bubbling for 30 minutes, ethyl 2-bromoisobutyrate (5.68 μL, 0.04 mmol) was added and polymerized at 40° C. for 4 hours. The polymer at this stage had Mn=22,700 and Mw/Mn=1.3. Then, 3-(4-azidophenoxy)propyl methacrylate (0.66 g, 2.53 mmol), 2,2′-bipyridine (464 mg, 2.97 mmol), copper (I) bromide (181 mg, 1.5 mmol) was added to 6 mL of ethanol. 26 mmol) was added, and the polymerization was continued at 50° C. for 7.5 hours. The polymerization reaction solution was dropped into 200 mL of THF for reprecipitation, and the precipitated polymer was washed with a THF/methanol 10/1 (volume ratio) solution. After that, it was dissolved in methanol, the copper catalyst was removed by adsorption with silica gel, and dried under reduced pressure to obtain a block copolymer of yellow-brown powder. The resulting block copolymer had Mn=28,700 and Mw/Mn=1.2. The composition ratio was determined from the integral ratio of ¹ H-NMR, and the value of m/(m+n) in the following structural formula (6) was 0.15.
Structural formula of block copolymer (6)

Example 7 [Immobilization on hydrophobic polymer film surface]
The film was surface-modified in the same manner as in Example 2, except that the block copolymer synthesized in Example 6 was used.

Example 8 [Evaluation of surface hydrophilicity (wettability) by water contact angle measurement]
When the contact angle was measured in the same manner as in Example 3 except that the film whose surface was modified in Example 7 was used, the contact angle to water was 7.1°.

Example 9 [Immobilization to porous membrane]
A surface-modified PVDF porous membrane was obtained in the same manner as in Example 4, except that the block copolymer synthesized in Example 6 was used.

Example 10 [Confirmation of protein adsorption amount suppression effect]
The amount of insulin adsorbed was measured in the same manner as in Example 5 except that the PVDF porous membrane prepared in Example 9 was used, and it was 0.16 μg/cm ² .

Comparative Example 1 [Synthesis of random copolymer]
2-methacryloyloxyethylphosphorylcholine (2.0 g, 6.8 mmol) and 3-(4-azidophenoxy) propyl methacrylate (0.18 g, 0.68 mmol) were placed in a glass 50 mL two-necked flask, and 2, 2'-Azobisisobutyronitrile (AIBN) (5.5 mg) was weighed. After 12.6 mL of methanol was added and dissolved, the oxygen in the solution was sufficiently removed with nitrogen, and the reaction was carried out at 60° C. for 5 hours using a water bath. After completion of the reaction, the mixture was diluted with 10 mL of methanol, added to 240 mL of THF, and unreacted monomers were removed by a reprecipitation method. By drying under reduced pressure, 1.58 g of a random copolymer was obtained as pale yellowish white powder. The resulting polymer had Mn=207,400 and Mw/Mn=2.3. The composition ratio was determined from the integral ratio of ¹ H-NMR, and the value of m/(m+n) in the following structural formula (7) was 0.09.

Structural formula of random copolymer (7)

Comparative Example 2 [Immobilization on Hydrophobic Polymer Film Surface]
A film was surface-modified in the same manner as in Example 2, except that the random copolymer synthesized in Comparative Example 1 was used.

Comparative Example 3 [Evaluation of surface hydrophilicity (wettability) by water contact angle measurement]
When the contact angle was measured in the same manner as in Example 3 except that the film whose surface was modified in Comparative Example 2 was used, the contact angle to water was 12.0°.

Comparative Example 4 [Immobilization to porous membrane]
A surface-modified PVDF porous membrane was obtained in the same manner as in Example 4, except that the random copolymer synthesized in Comparative Example 1 was used.

Comparative Example 5 [Confirmation of protein adsorption amount suppression effect]
The amount of insulin adsorbed was measured in the same manner as in Example 5, except that the PVDF porous membrane prepared in Comparative Example ⁴ was used.

The surface of a hydrophobic film can be efficiently and easily modified to be hydrophilic, and the film has various functions, such as imparting wettability to electrolyte solutions, suppressing protein adsorption, preventing biofouling, Adsorption prevention of medicinal ingredients, antithrombogenicity, biocompatibility, antistatic properties, etc. can be imparted. Such properties are particularly useful in agricultural applications, civil engineering and construction applications, water treatment applications, and optical applications that require durability to maintain high functionality for a long period of time, and can be widely used in this field of application.

Claims (2)

A block copolymer having a structure represented by the following general formula (1) and having a number average molecular weight of 1,000 to 1,000,000.

(Wherein, m and n independently represent an integer of 1 or more, the value of m/(m+n) is 0.02 to 0.15 , and Z is -O- or -N(R ₃ )- A represents a group represented by —O— or —CH ₂ —, and R ₁ , R ₂ and R ₃ each independently represent a hydrogen atom or a C ₁ to C ₆ hydrocarbon group. R ₄ represents a C ₃ to C ₆ divalent hydrocarbon group, R ₅ represents a fluorine atom, and p represents an integer of 0 to 4.) 2. The block copolymer according to claim 1, wherein in the general formula (1), Z and A are groups represented by -O-.