Polymers containing ethylene oxide chains

Abstract

[Problem] To provide an oxyethylene chain-containing polymer having excellent biocompatibility and excellent reactivity. [Solution] This oxyethylene chain-containing polymer is represented by general formula (1) (in general formula (1), R1 is-(CH2) p-SH,-(CH2) p-N3,-(CH2) p-NH2, or-(CH2) p-COOH, p is an integer of 1-5, R2 to R4 are each independently hydrogen or an alkyl group having 1-10 carbon atoms, R5 is an alkyl group having 1-10 carbon atoms, R6 is hydrogen or an alkyl group having 1-5 carbon atoms, R7 is an alkyl group having 1-10 carbon atoms, n is an integer of 5-1000, m is an integer of 1-10, and q is an integer of 0-5. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to polymers containing oxyethylene chains. Background Art

[0002] Conventionally, vinyl ether polymers have been used as a component of chemicals such as adhesives, coatings, and lubricants. It is known that vinyl ethers generally have electron-donating substituents, and therefore vinyl ether polymers are obtained by cationic polymerization. For the purpose of modifying vinyl ether polymers, polymerization methods for introducing functional groups at the ends have been studied. For example, it has been proposed to introduce acetal groups at the ends of vinyl ether polymers (see Patent Documents 1 and 2).

[0003] In addition, the polymer of oxyethylene chain is a material with excellent biocompatibility. In order to utilize the polymer of oxyethylene chain as biomaterial, it is indispensable to introduce a highly reactive functional group. However, it is not known to introduce a polymer of oxyethylene chain with a highly reactive functional group at the end. Therefore, it is desirable to develop a polymer of oxyethylene chain with excellent biocompatibility and excellent reactivity.

[0004] Prior art literature

[0005] Patent Literature

[0006] Patent Document 1: Japanese Patent Application Publication No. 2003-201315

[0007] Patent Document 2: Japanese Patent Application Publication No. 2004-244535 Summary of the invention

[0008] Problems to be solved by the invention

[0009] Therefore, an object of the present invention is to provide an oxyethylene chain-containing polymer having excellent biocompatibility and excellent reactivity.

[0010] Means for solving problems

[0011] The inventors of the present application have conducted intensive studies to solve the above problems and have found that the above problems can be solved by introducing a highly reactive specific functional group into one end (ω end) of an oxyethylene chain-containing polymer, thereby completing the present invention.

[0012] That is, according to the present invention, the following inventions are provided.

[0013] [1] A polymer containing an oxyethylene chain, which is represented by the following general formula (1):

[0014] [Chemical formula 1]

[0015]

[0016] (In general formula (1), R 1 -(CH2) p -SH, -(CH2) p -N3, -(CH2) p -NH2, or -(CH2) p -COOH, p is an integer from 1 to 5,

[0017] R 2 ~R 4 are each independently hydrogen or an alkyl group having 1 to 10 carbon atoms,

[0018] R 5 is an alkyl group having 1 to 10 carbon atoms,

[0019] R 6 is hydrogen or an alkyl group having 1 to 5 carbon atoms,

[0020] R 7 is an alkyl group having 1 to 10 carbon atoms,

[0021] n is an integer from 5 to 1000,

[0022] m is an integer from 1 to 10,

[0023] q is an integer from 0 to 5).

[0024] [2] The oxyethylene chain-containing polymer according to [1], wherein in the general formula (1), R 1 -(CH2) p -SH, p is an integer from 1 to 3,

[0025] R 2 ~R 4 are each independently hydrogen or an alkyl group having 1 to 4 carbon atoms,

[0026] R 5 is an alkyl group having 1 to 4 carbon atoms,

[0027] R 6 is an alkyl group having 1 to 2 carbon atoms,

[0028] R 7 is an alkyl group having 1 to 7 carbon atoms,

[0029] n is an integer from 10 to 500,

[0030] m is an integer from 1 to 5,

[0031] q is an integer from 0 to 2.

[0032] [3] The oxyethylene chain-containing polymer according to [1], wherein in the general formula (1), R 1 -(CH2)p -N3, p is an integer from 1 to 3,

[0033] R 2 ~R 4 are each independently hydrogen or an alkyl group having 1 to 4 carbon atoms,

[0034] R 5 is an alkyl group having 1 to 4 carbon atoms,

[0035] R 6 is an alkyl group having 1 to 2 carbon atoms,

[0036] R 7 is an alkyl group having 1 to 7 carbon atoms,

[0037] n is an integer from 10 to 500,

[0038] m is an integer from 1 to 5,

[0039] q is an integer from 0 to 2.

[0040] [4] The polymer containing oxyethylene chains as described in [1], wherein in the general formula (1), R 1 -(CH2) p -NH2, p is an integer from 1 to 3,

[0041] R 2 ~R 4 are each independently hydrogen or an alkyl group having 1 to 4 carbon atoms,

[0042] R 5 is an alkyl group having 1 to 4 carbon atoms,

[0043] R 6 is an alkyl group having 1 to 2 carbon atoms,

[0044] R 7 is an alkyl group having 1 to 7 carbon atoms,

[0045] n is an integer from 10 to 500,

[0046] m is an integer from 1 to 5,

[0047] q is an integer from 0 to 2.

[0048] [5] The oxyethylene chain-containing polymer according to [1], wherein in the general formula (1), R 1 -(CH2) p -COOH, p is an integer from 1 to 3,

[0049] R 2 ~R 4 are each independently hydrogen or an alkyl group having 1 to 4 carbon atoms,

[0050] R 5 is an alkyl group having 1 to 4 carbon atoms,

[0051] R 6 is an alkyl group having 1 to 2 carbon atoms,

[0052] R 7 is an alkyl group having 1 to 7 carbon atoms,

[0053] n is an integer from 10 to 500,

[0054] m is an integer from 1 to 5,

[0055] q is an integer from 0 to 2.

[0056] [6] The oxyethylene chain-containing polymer according to any one of [1] to [5], wherein the number average molecular weight (Mn) of the oxyethylene chain-containing polymer is 500 or more and 100,000 or less.

[0057] [7] The oxyethylene chain-containing polymer according to any one of [1] to [6], wherein the ratio of the weight average molecular weight (Mw) to the number average molecular weight (Mn) of the oxyethylene chain-containing polymer is 1.0 to 3.0.

[0058] Effects of the Invention

[0059] According to the present invention, a polymer containing an oxyethylene chain having excellent biocompatibility and excellent reactivity can be provided. Such a polymer containing an oxyethylene chain can be easily modified on a substrate, microparticles, etc. due to its excellent reactivity, and can impart biocompatibility to the substrate, microparticles, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0060] [ Figure 1 ] is the reaction product (polymer containing ethylene oxide chain) and its precursor measured in Example 1 1 H-NMR spectrum.

[0061] [ Figure 2 ] is the reaction product (polymer containing ethylene oxide chain) and its precursor measured in Example 2 1 H-NMR spectrum. DETAILED DESCRIPTION

[0062] <Polymers containing ethylene oxide chains>

[0063] The oxyethylene chain-containing polymer of the present invention is represented by the following general formula (1).

[0064] [Chemical formula 2]

[0065]

[0066] In the general formula (1), R1 -(CH2) p -SH, -(CH2) p -N3, -(CH2) p -NH2, or -(CH2) p -COOH.

[0067] p is an integer of 1-5, preferably an integer of 1-3, and more preferably 1 or 2.

[0068] R 2 ~R 4 Each is independently hydrogen or an alkyl group having 1 to 10 carbon atoms, preferably hydrogen or an alkyl group having 1 to 4 carbon atoms, more preferably hydrogen or an alkyl group having 1 to 3 carbon atoms, further preferably hydrogen or an alkyl group having 1 to 2 carbon atoms, and still more preferably hydrogen.

[0069] R 5 It is an alkyl group having 1 to 10 carbon atoms, preferably an alkyl group having 1 to 10 carbon atoms, more preferably an alkyl group having 1 to 4 carbon atoms, and further preferably an alkyl group having 1 to 2 carbon atoms.

[0070] R 6 It is hydrogen or an alkyl group having 1 to 5 carbon atoms, preferably an alkyl group having 1 to 2 carbon atoms, and more preferably a methyl group.

[0071] R 7 The alkyl group is an alkyl group having 1 to 10 carbon atoms, preferably an alkyl group having 1 to 7 carbon atoms, and more preferably an alkyl group having 1 to 4 carbon atoms.

[0072] n is an integer of 5 to 1000, preferably an integer of 10 to 500, and more preferably an integer of 20 to 400.

[0073] m is an integer of 1-10, preferably an integer of 1-5, and more preferably an integer of 1-3.

[0074] q is an integer of 0-5, preferably an integer of 0-2, and more preferably an integer of 0-1.

[0075] It should be noted that the above-mentioned alkyl group may be linear or branched.

[0076] As for the polymer containing oxyethylene chain of the present invention, by introducing a thiol group, an azido group, an amino group, or a carboxyl group as a highly reactive functional group at a single end (ω end), it is possible to modify a substrate, microparticles, etc. while making the biocompatibility excellent. Therefore, biocompatibility can be imparted to the substrate, microparticles, etc. In addition, these highly reactive functional groups can also be further converted to further improve the performances such as reactivity and modifiability.

[0077] Preferred embodiments of the oxyethylene chain-containing polymer represented by the general formula (1) include the following polymers: In the following formula, n is an integer of 5 to 1000, preferably an integer of 10 to 500, and more preferably an integer of 20 to 400.

[0078] [Chemical formula 3]

[0079]

[0080] [Chemical formula 4]

[0081]

[0082] [Chemical formula 5]

[0083]

[0084] [Chemical formula 6]

[0085]

[0086] The number average molecular weight (Mn) of the polymer containing an oxyethylene chain of the present invention is preferably 500 to 100,000. The lower limit of the number average molecular weight (Mn) is more preferably 700 or more, more preferably 1,000 or more, and more preferably 1,500 or more. In addition, the upper limit is more preferably 70,000 or less, more preferably 50,000 or less, more preferably 30,000 or less, and particularly preferably 20,000 or less. If the number average molecular weight (Mn) of the polymer containing an oxyethylene chain is within the above range, the biocompatibility is excellent, and it is easy to modify the substrate, microparticles, etc., and it is easy to impart biocompatibility.

[0087] The ratio of the weight average molecular weight (Mw) to the number average molecular weight (Mn) of the polymer containing an oxyethylene chain of the present invention (molecular weight distribution, Mw / Mn) is preferably 1.0 to 3.0, more preferably 1.0 to 2.0, further preferably 1.0 to 1.5, and further preferably 1.0 to 1.3. If the molecular weight distribution (Mw / Mn) of the polymer containing an oxyethylene chain is within the above range, the performance of the polymer can be easily kept uniform.

[0088] In addition, in the present invention, the number average molecular weight (Mn) and the weight average molecular weight (Mw) can be calculated from a standard polystyrene calibration curve using a gel permeation chromatography (GPC) method.

[0089] <Method for producing oxyethylene chain-containing polymer>

[0090] The embodiment of the method for producing a polymer containing an oxyethylene chain of the present invention is described. First, using vinyl ether as a raw monomer, in the presence of a polymerization initiator, living cationic polymerization is used to synthesize, for example, a polymer containing an oxyethylene chain having a carbonyl group at one end represented by the following general formula (2). At the end of the polymerization, a small amount of water is added, whereby the terminal cation reacts with water to introduce a carbonyl group. Next, the carbonyl group at one end of the polymer containing an oxyethylene chain represented by the following general formula (2) is converted, thereby introducing a reactive functional group (thiol group, azido group, amino group, or carboxyl group).

[0091] [Chemical formula 7]

[0092]

[0093] It should be noted that in the general formula (2), R 2 ~R 7 , n, m, and q are the same as R in the general formula (1) 2 ~R 7 , n, m, and q are the same.

[0094] In general formula (2), R 2 ~R 7 The preferred embodiments of n, m, and q are also the same as those of R in the general formula (1). 2 ~R 7 The preferred aspects of , n, m, and q are the same.

[0095] As the vinyl ether as the raw material monomer, for example, a vinyl ether represented by the following general formula (3) can be used:

[0096] [Chemical formula 8]

[0097]

[0098] In the general formula (3), R 2 ~R 5 , and m and R in the general formula (1) 2 ~R 5 , and m are the same.

[0099] In general formula (2), R 2 ~R 5 The preferred embodiments of , and m are also the same as those of R in the general formula (1). 2 ~R 5 , and m are the same.

[0100] Examples of the vinyl ether represented by the general formula (3) include 2-methoxyethyl vinyl ether (MOVE), 2-ethoxyethyl vinyl ether (EOVE), diethylene glycol monoethyl monovinyl ether (EOEOVE), and triethylene glycol monomethyl vinyl ether (TEGMVE).

[0101] The polymerization initiator used in the polymerization of the polymer of oxyethylene chain is not particularly limited as long as cationic polymerization is actively carried out, and polymerization initiators known in the past can be used.As polymerization initiator, for example, HI / I2 system initiator (for example, Japanese Patent Laid-Open No. 60-228509 publication), polymerization initiator (for example, Japanese Patent No. 3096494 specification, Japanese Patent No. 7-2805 publication, Japanese Patent Laid-Open No. 62-257910 publication, Japanese Patent Laid-Open No. 1-108202 publication and Japanese Patent Laid-Open No. 1-108203 publication) etc., which are preferably used as active cationic polymerization initiators of vinyl ethers, can be preferably used.

[0102] The amount of the polymerization initiator used is preferably 0.001 to 20 mol %, more preferably 0.01 to 10 mol %, particularly preferably 1 mol % or less, based on the total amount of the raw material monomers.

[0103] In addition, the living cationic polymerization reaction is preferably carried out under the condition of the presence of a suitable organic solvent, but it can also be carried out under the condition of the absence of a suitable organic solvent. As the usable organic solvent, for example, aromatic hydrocarbon solvents such as benzene, toluene, and xylene can be cited; aliphatic hydrocarbon solvents such as propane, n-butane, isobutane, n-pentane, isopentane, n-hexane, n-heptane, n-octane, isooctane, decane, hexadecane, and cyclohexane; halogenated hydrocarbon solvents such as dichloromethane, ethylene chloride, and carbon tetrachloride; ether solvents such as ether, dibutyl ether, tetrahydrofuran (THF), dioxane, and ethylene glycol diethyl ether. These organic solvents can be used alone or in combination of two or more as needed. In addition, among these organic solvents, hydrocarbon solvents such as aromatic hydrocarbon solvents and aliphatic hydrocarbon solvents are preferred, preferably toluene, THF, etc.

[0104] The polymerization temperature in the living cationic polymerization reaction varies according to the type of polymerization initiator, monomer, solvent, etc. used, and is usually -80 to 150°C, preferably -50 to 100°C, and particularly preferably -20 to 80°C. In addition, the polymerization time varies according to the polymerization initiator, monomer, solvent, reaction temperature, etc. used, and is usually about 10 minutes to 100 hours. The polymerization reaction can be suitably carried out by any method in a batch type or a continuous type. After the polymerization reaction, in order to remove the unreacted monomer, a purification treatment can be carried out by a known method as needed.

[0105] Below, an example of the polymerization reaction of a polymer containing an oxyethylene chain (PMOVE) using 2-methoxyethyl vinyl ether (MOVE) as a raw material monomer is shown. First, MOVE is used in the presence of a polymerization initiator to synthesize PMOVE having a carbonyl group at one end using the following reaction formula (I). A small amount of water is added at the end of the polymerization, whereby the terminal cation reacts with water to introduce a carbonyl group. The polymerization reaction conditions of the following reaction formula (I) can be referred to J.Polym.Sci., Part A:Polym.Chem.2005,43,468-472. It should be noted that in the following reaction formulas (I) to (V), n in PMOVE is an integer of 5 to 1000, similarly to the general formula (1), preferably an integer of 10 to 500, and more preferably an integer of 20 to 400.

[0106] [Chemical formula 9]

[0107]

[0108] Hereinafter, the synthesis method (reaction formula) of PMOVE is described according to the type of reactive functional group. The catalyst, polymerization initiator, and solvent in the following series of reactions can be appropriately selected with reference to the known methods. In addition, polymerization reaction conditions such as polymerization temperature and polymerization time can be appropriately set.

[0109] When the reactive functional group is a thiol group, the carbonyl group at one end of the PMOVE obtained above is changed as shown in the following reaction formula (II), and a PMOVE having a thiol group at one end can be synthesized. The polymerization reaction conditions of the following reaction formula (II) can be referred to Journal of Colloid and Interface Science 428 (2014) 276-285. It should be noted that in the following reaction formula (II), EtOH represents ethanol, MsCl represents methanesulfonyl chloride, TEA represents triethylamine, KSAc represents potassium thioacetate, DMSO represents dimethyl sulfoxide, MeOH represents methanol, and NaOH represents sodium hydroxide.

[0110] [Chemical formula 10]

[0111]

[0112] When the reactive functional group is an azido group, the carbonyl group at one end of the PMOVE obtained above is changed as shown in the following reaction formula (III), and a PMOVE having an azido group at one end can be synthesized. The polymerization reaction conditions of the following reaction formula (III) can be referred to Med Chem Res (2016) 25: 824-833. It should be noted that in the following reaction formula (III), NaN3 is sodium azide, and the other abbreviations are the same as those in the above reaction formula (II).

[0113] [Chemical formula 11]

[0114]

[0115] When the reactive functional group is an amino group, the carbonyl group at one end of the PMOVE obtained above is changed as shown in the following reaction formula (IV), and a PMOVE having an amino group at one end can be synthesized. The polymerization reaction conditions of the following reaction formula (IV) can be referred to Med Chem Res (2016) 25: 824-833. It should be noted that in the following reaction formula (IV), PPh3 is triphenylphosphine, and the other abbreviations are the same as those in the above reaction formula (II).

[0116] [Chemical formula 12]

[0117]

[0118] When the reactive functional group is a carboxyl group, the carbonyl group at one end of the PMOVE obtained above is modified as shown in the following reaction formula (IV) to synthesize a PMOVE having a carboxyl group at one end. It should be noted that in the following reaction formula (V), NaClO2 represents sodium chlorite, and NaH2PO4 represents sodium dihydrogen phosphate.

[0119] [Chemical formula 13]

[0120]

[0121] Example

[0122] Next, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited to these Examples and the like.

[0123] It should be noted that in the embodiments and comparative examples, the structure of the polymer is based on 1 The number average molecular weight (Mn) and molecular weight distribution (Mw / Mn) of the polymer were obtained from the molecular weight analysis results (in terms of polystyrene) of GPC. The analytical equipment and measurement conditions for each measurement are shown below.

[0124] (NMR measurement conditions)

[0125] Device: Made by JEOL, Model: ECS-400

[0126] Solvent: deuterated chloroform

[0127] ·Measurement temperature: 25℃

[0128] (GPC measurement conditions)

[0129] ·Device: Made by Tosoh Corporation, "HLC-8320GPC"

[0130] Detector: RI detector

[0131] Mobile phase: tetrahydrofuran

[0132] Flow rate: 1mL / min

[0133] ·Chromatographic column: 3 pieces of "Shodex LF-804" manufactured by Showa Denko K.K.

[0134] Column temperature: 40°C

[0135] [Example 1]

[0136] Synthesis of a polymer containing an oxyethylene chain having a thiol group at one end (PMOVE-SH) (reaction formula (I) + (II)

[0137] 2-Methoxyethyl vinyl ether (MOVE) was used as a raw material monomer, and as shown in the above reaction formula (I), PMOVE (PMOVE-CHO) having a carbonyl group at one end was obtained. Specifically, 5.8 mL of MOVE as a raw material monomer, 147 μL of MOEA, an acetic acid adduct of MOVE as a polymerization initiator, 90 mL of toluene, 1.6 mL of THF, 108 μL of 2,6-di-tert-butylpyridine, 2.2 mL of ethyl aluminum sesquichloride (25% toluene solution), and 1.0 mL of tin (IV) chloride (1.0 M heptane solution) were added to carry out a polymerization reaction. At the end of the polymerization, 1.0 mL of water was added to introduce a carbonyl group at one end. The solvent was removed with an evaporator, and after being dissolved in ethanol again, it was purified using a 0.45 μm syringe filter. The solvent was removed again to obtain PMOVE-CHO.

[0138] In addition, in this specification, a polymer having a functional group at one end is referred to as "polymer name-functional group name".

[0139] Next, as shown in the above reaction formula (II), the carbonyl group at one end of PMOVE is changed to a thiol group. Specifically, first add 1.0 g of PMOVE-CHO, 0.3 g of sodium borohydride, and 20 mL of ethanol and stir overnight. Dissolve it in water and dialysis and purify it with a dialysis membrane of MWCO=3,500 to obtain PMOVE-OH. Next, add 500 mg of PMOVE-OH, 12 mL of CH2Cl2, 63 μL of TEA, and 23 μL of MsCl, react at 0°C for 0.5 hours under an argon atmosphere, and further react at room temperature for 3.5 hours. Wash with water and saturated brine, and remove the solvent with an evaporator to obtain PMOVE-Ms. Next, add 500 mg of PMOVE-Ms, 12 mL of dehydrated DMSO, and 57 mg of KSAc, and react at 40°C for 18 hours under an argon atmosphere. After quenching with 1.0 M hydrochloric acid, remove the solvent. Dissolve it in water again and purify it by dialyzing with a dialysis membrane of MWCO=3,500 to obtain PMOVE-SAc. Finally, add 500 mg of PMOVE-SAc and 12 mL of dehydrated methanol and bubble with argon. Add 20 mg of NaOH and 46 mg of dithiothreitol to it and react for 1 hour. After quenching with 1.0 M hydrochloric acid, use a dialysis membrane of MWCO=3,500 to purify it by dialyzing in a refrigerator at 4°C to obtain PMOVE-SH.

[0140] The obtained reaction product (PMOVE-SH) and its precursor (PMOVE-SAc) were subjected to the above conditions. 1 H-NMR measurement, we get Figure 1 shown 1 H-NMR spectrum. Figure 1 The upper figure is the spectrum of the precursor. Figure 1 The lower figure is the spectrum of the reaction product. As a result of the spectrum analysis, in the spectrum of the precursor, a peak from the methylene group (CH2) adjacent to the thioacetyl group (SCOCH3) can be confirmed ( Figure 1 ※1) in the upper figure of is located at 2.90 ppm, but in the spectrum of the reaction product, a peak derived from a methylene group adjacent to a thiol group can be confirmed ( Figure 1 ※3) in the lower figure of the figure shifted to 2.60 ppm. In addition, in the spectrum of the precursor, it can be confirmed that the peak derived from the thioacetyl group ( Figure 1 ※2) in the upper figure of the figure is located at 2.30 ppm, but the peak derived from the thioacetyl group disappears in the spectrum of the reaction product. Based on these results, it was confirmed that a thiol group was introduced into one end of PMOVE. In addition, compared with the integral value of the peak derived from the methyl group at the α end (※A), the introduction rate of the thiol group into one end was about 100%.

[0141] The number average molecular weight (Mn) and molecular weight distribution (Mw / Mn) of PMOVE-SH obtained above were measured, and the results were Mn=5,000 and Mw / Mn=1.05.

[0142] [Example 2]

[0143] Synthesis of a polymer containing an oxyethylene chain having an azide group at one end (PMOVE-N3) (Reaction formula (I) + (III))

[0144] PMOVE-CHO was obtained by the same operation as in Example 1. Then, as shown in the above reaction formula (III), the carbonyl group at one end of PMOVE was changed to an azido group. Specifically, 500 mg of PMOVE-Ms, 12 mL of dehydrated DMSO, and 39 mg of NaN3 were added, and the reaction was carried out at 70°C for 18 hours under an argon atmosphere. After quenching with water, the solvent was removed. It was dissolved in water again and purified by dialyzing with a dialysis membrane with MWCO=3,500 to obtain PMOVE-N3.

[0145] The reaction product (PMOVE-N3) and its precursor (PMOVE-Ms) obtained above were subjected to the above conditions. 1 H-NMR measurement, we get Figure 2 shown 1 H-NMR spectrum. Figure 2 The upper figure is the spectrum of the precursor. Figure 2 The lower figure is the spectrum of the reaction product. As a result of the spectrum analysis, in the spectrum of the precursor, it is possible to confirm the peak of the methyl group (CH3) in the methylsulfonyl group (CH3SO2) ( Figure 2 ※4) in the upper figure of the reaction product is located at 3.24ppm, but in the spectrum of the reaction product, the peak derived from the methyl group in the methylsulfonyl group disappears. In addition, in the spectrum of the reaction product, the peak derived from the ethylene group (CH2CH2) adjacent to the azido group can be confirmed ( Figure 2 ※5, 6) in the lower figure of is located at 3.40 to 3.50 ppm. Based on these results, it was confirmed that an azido group was introduced at one end of PMOVE. In addition, the integral value of the peak (※A) from the methyl group at the α end was calculated, and the result showed that the introduction rate of the methylsulfonyl group to one end of the precursor was about 100%.

[0146] The number average molecular weight (Mn) and molecular weight distribution (Mw / Mn) of PMOVE-N3 obtained above were measured, and the results were Mn=5,000 and Mw / Mn=1.05.

[0147] [Example 3]

[0148] Synthesis of a polymer containing an oxyethylene chain having an amino group at one end (PMOVE-NH2) (reaction formula (I) + (IV))

[0149] PMOVE-CHO was obtained by the same operation as in Example 1. Then, as shown in the above reaction formula (IV), the carbonyl group at one end of PMOVE was changed to an amino group. Specifically, 500 mg of PMOVE-N3, 525 mg of PPh3, 8.7 mL of MeOH, and 3.3 mL of water were added, refluxed at 90°C, and reacted for 5 hours. After quenching with 1.0 M hydrochloric acid, the solvent was removed. It was dissolved in water again and purified by dialyzing with a dialysis membrane with MWCO=3,500 to obtain PMOVE-NH2.

[0150] The PMOVE-NH2 obtained above was quantitatively analyzed by GPC (RI detector: RI-2031 Plus (manufactured by JASCO Corporation), GPC pump: PU-1580 (manufactured by JASCO Corporation, mobile phase: 2 mM NaCl aqueous solution) using a cation exchange column (SP-5PW). The result showed that the introduction rate of the amino group to one terminal was about 100%. In addition, based on this result, it is estimated that the introduction rate of the azide group to one terminal in the polymer having an azide group at one terminal of Example 2, which is a precursor of the polymer having an amino group at one terminal of Example 3, is about 100%.

[0151] The number average molecular weight (Mn) and molecular weight distribution (Mw / Mn) of PMOVE-NH2 obtained above were measured, and the results were Mn=5,000 and Mw / Mn=1.05.

[0152] [Example 4]

[0153] Synthesis of a polymer containing an oxyethylene chain having a carboxyl group at one end (PMOVE-COOH) (reaction formula (I) + (V))

[0154] PMOVE-CHO was obtained by the same operation as in Example 1. Then, as shown in the above reaction formula (V), the carbonyl group at one end of PMOVE was changed to a carboxyl group. Specifically, 500 mg of PMOVE-CHO, 5.5 mL of ethanol, and 0.2 mL of 2-methyl-2-butene were added, stirred thoroughly and cooled to 0°C. Then, 34 mg of NaClO2, 36 mg of NaH2PO4, and 0.9 mL of water were added to another flask and stirred thoroughly. The aqueous solution was added dropwise to the ethanol solution, stirred for 5 minutes, and further reacted at room temperature for 15 hours. After quenching with saturated brine, it was dialyzed and purified using a dialysis membrane with MWCO=3,500 to obtain PMOVE-COOH.

[0155] use 1 The PMOVE-COOH obtained above was measured by H-NMR, and as a result, it was confirmed that a carboxyl group was introduced at one terminal. In addition, the introduction rate of the carboxyl group at one terminal was about 100%.

[0156] The number average molecular weight (Mn) and molecular weight distribution (Mw / Mn) of PMOVE-COOH obtained above were measured, and the results were Mn=5,000 and Mw / Mn=1.05.

[0157] [Example 5]

[0158] Synthesis of a polymer containing an oxyethylene chain having a thiol group at one end (PMOVE-SH) (reaction formula (I) + (II)

[0159] PMOVE-SH was obtained in the same manner as in Example 1 except that 55.7 μL of MOEA was added.

[0160] The number average molecular weight (Mn) and molecular weight distribution (Mw / Mn) of PMOVE-SH obtained above were measured, and the results were Mn=12,000 and Mw / Mn=1.04.

[0161] [Example 6]

[0162] Synthesis of a polymer containing an oxyethylene chain having a thiol group at one end (PMOVE-SH) (reaction formula (I) + (II)

[0163] PMOVE-SH was obtained in the same manner as in Example 1 except that 3.5 mL of MOVE, 230 μL of MOEA, 138 mL of toluene, 2.4 mL of THF, 162 μL of 2,6-di-tert-butylpyridine, 3.3 mL of ethylaluminum sesquichloride (25% toluene solution), and 1.5 mL of tin (IV) chloride (1.0 M heptane solution) were added.

[0164] The number average molecular weight (Mn) and molecular weight distribution (Mw / Mn) of PMOVE-SH obtained above were measured, and the results were Mn=2,000 and Mw / Mn=1.06.

[0165] [Example 7]

[0166] Synthesis of a polymer containing an oxyethylene chain having a thiol group at one end (PEOVE-SH) (Reaction formula (I) + (II)

[0167] PEOVE-SH was obtained in the same manner as in Example 1 except that 6.5 mL of 2-ethoxyethyl vinyl ether (EOVE) as a raw material monomer and 203 μL of EOEA, which is an acetic acid adduct of EOVE, as an initiator were added.

[0168] The number average molecular weight (Mn) and molecular weight distribution (Mw / Mn) of the PEOVE-SH obtained above were measured, and the results were Mn=5,000 and Mw / Mn=1.08.

[0169] [Example 8]

[0170] Synthesis of a polymer containing an oxyethylene chain having a thiol group at one end (PEOEOVE-SH) (Reaction formula (I) + (II)

[0171] PEOEOVE-SH was obtained in the same manner as in Example 1 except that 8.7 mL of 2-(2-ethoxy)ethoxyethyl vinyl ether (EOEOVE) as a raw material monomer and 333 μL of EOEOEA, which is an acetic acid adduct of EOEOVE, as an initiator were added.

[0172] The number average molecular weight (Mn) and molecular weight distribution (Mw / Mn) of the PEOEOVE-SH obtained above were measured, and the results were Mn=5,000 and Mw / Mn=1.06.

[0173] [Example 9]

[0174] Synthesis of a polymer containing an oxyethylene chain having a thiol group at one end (PTEGMVE-SH) (Reaction formula (I) + (II)

[0175] PTEGMVE-SH was obtained in the same manner as in Example 1 except that 9.6 mL of triethylene glycol monomethyl vinyl ether (TEGMVE) as a raw material monomer and 450 μL of TEGMEA, which is an acetic acid adduct of TEGMVE, as an initiator were added.

[0176] The number average molecular weight (Mn) and molecular weight distribution (Mw / Mn) of the PTEGMVE-SH obtained above were measured, and the results were Mn=5,000 and Mw / Mn=1.08.

[0177] [Comparative Example 1]

[0178] Synthesis of a polymer containing an oxyethylene chain having a carbonyl group at one end (PMOVE-CHO) (Reaction formula (I))

[0179] The same operation as in Example 1 was carried out to obtain PMOVE-CHO.

[0180] The number average molecular weight (Mn) and molecular weight distribution (Mw / Mn) of the PMOVE-CHO obtained above were measured, and the results were Mn=5,000 and Mw / Mn=1.05.

[0181] [Comparative Example 2]

[0182] Synthesis of poly(n-butyl vinyl ether) having a thiol group at one end (PNBVE-SH)

[0183] PNBVE-SH was obtained in the same manner as in Example 1 except that n-butyl vinyl ether (NBVE) was used as the raw material monomer instead of 2-methoxyethyl vinyl ether (MOVE).

[0184] The number average molecular weight (Mn) and molecular weight distribution (Mw / Mn) of the PNBVE-SH obtained above were measured, and the results were Mn=5,000 and Mw / Mn=1.10.

[0185] (Polymer Performance Evaluation)

[0186] Gold microparticles coated with PMOVE (PMOVE-coated gold microparticles) were obtained by modifying gold microparticles having an average particle size of 150 nm using PMOVE-SH obtained in Example 1. Specifically, the following test was performed.

[0187] Test method:

[0188] The dispersion of 150 nm gold microparticles modified with citric acid was concentrated by centrifugation and then dispersed in 90 μL of water. 2 10 μL of PMOVE-SH prepared in the manner of 10 μL was reacted at 60°C for 1 hour. After the reaction, the mixture was concentrated by centrifugation and the supernatant was removed. Then, the mixture was washed several times with water containing 0.25 mM sodium citrate and 0.05 v / v% Tween 20.

[0189] The average particle size of the PMOVE-coated gold microparticles obtained in the above experiment was measured by dynamic light scattering using a particle size measuring device (Malvern Panalytical, model: Zetasizer Nano Zs). The result showed that the average particle size increased to 175.6 nm. Based on this result, it is speculated that PMOVE can be modified on the surface of gold microparticles.

[0190] An attempt was made to modify gold microparticles according to the above-mentioned test method using PMOVE-CHO obtained in Comparative Example 1. However, since the polymer had low reactivity with gold microparticles, it did not bond to the terminal and could not modify the gold microparticles.

[0191] An attempt was made to modify gold microparticles according to the above-mentioned test method using PNBVE-SH obtained in Comparative Example 2. However, since the polymer is hydrophobic, it agglomerated and could not modify the gold microparticles.

Claims

1. A polymer containing ethylene oxide chains, which is represented by the following general formula (1): [Chemical formula 1] In the general formula (1), R 1 -(CH2) p -SH, -(CH2) p -N3, -(CH2) p -NH2, or -(CH2) p -COOH, p is an integer from 1 to 5, R 2 ~R 4 are each independently hydrogen or an alkyl group having 1 to 10 carbon atoms, R 5 is an alkyl group having 1 to 10 carbon atoms, R 6 is hydrogen or an alkyl group having 1 to 5 carbon atoms, R 7 is an alkyl group having 1 to 10 carbon atoms, n is an integer from 5 to 1000, m is an integer from 1 to 10, q is an integer from 0 to 5.

2. The polymer containing oxyethylene chains according to claim 1, wherein In the general formula (1), R 1 -(CH2) p -SH, p is an integer from 1 to 3, R 2 ~R 4 are each independently hydrogen or an alkyl group having 1 to 4 carbon atoms, R 5 is an alkyl group having 1 to 4 carbon atoms, R 6 is an alkyl group having 1 to 2 carbon atoms, R 7 is an alkyl group having 1 to 7 carbon atoms, n is an integer from 10 to 500, m is an integer from 1 to 5, q is an integer from 0 to 2.

3. The polymer containing oxyethylene chains according to claim 1, wherein In the general formula (1), R 1 -(CH2) p -N3, p is an integer from 1 to 3, R 2 ~R 4 are each independently hydrogen or an alkyl group having 1 to 4 carbon atoms, R 5 is an alkyl group having 1 to 4 carbon atoms, R 6 is an alkyl group having 1 to 2 carbon atoms, R 7 is an alkyl group having 1 to 7 carbon atoms, n is an integer from 10 to 500, m is an integer from 1 to 5, q is an integer from 0 to 2.

4. The polymer containing oxyethylene chains according to claim 1, wherein In the general formula (1), R 1 -(CH2) p -NH2, p is an integer from 1 to 3, R 2 ~R 4 are each independently hydrogen or an alkyl group having 1 to 4 carbon atoms, R 5 is an alkyl group having 1 to 4 carbon atoms, R 6 is an alkyl group having 1 to 2 carbon atoms, R 7 is an alkyl group having 1 to 7 carbon atoms, n is an integer from 10 to 500, m is an integer from 1 to 5, q is an integer from 0 to 2.

5. The polymer containing oxyethylene chains according to claim 1, wherein In the general formula (1), R 1 -(CH2) p -COOH, p is an integer from 1 to 3, R 2 ~R 4 are each independently hydrogen or an alkyl group having 1 to 4 carbon atoms, R 5 is an alkyl group having 1 to 4 carbon atoms, R 6 is an alkyl group having 1 to 2 carbon atoms, R 7 is an alkyl group having 1 to 7 carbon atoms, n is an integer from 10 to 500, m is an integer from 1 to 5, q is an integer from 0 to 2.

6. The oxyethylene chain-containing polymer according to any one of claims 1 to 5, wherein The number average molecular weight (Mn) of the oxyethylene chain-containing polymer is 500 to 100,000.

7. The oxyethylene chain-containing polymer according to any one of claims 1 to 5, wherein The ratio of the weight average molecular weight (Mw) to the number average molecular weight (Mn) of the oxyethylene chain-containing polymer is 1.0 to 3.0.

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