JP4811650B2 - Thermosensitive polymer compound - Google Patents

Description

  The present invention relates to a thermosensitive polymer compound, and more particularly to a photoresponsive thermosensitive polymer compound.

Poly-N-isopropylacrylamide is used as a drug carrier in a drug delivery system due to the fact that the balance between hydrophilicity and hydrophobicity changes suddenly in an aqueous solution and causes a phase transition phenomenon (Patent Document 1, Patent Document) 2), protein adsorption / desorption membranes (Patent Literature 3), and chromatographic materials with varying affinity have been proposed (Patent Literature 4).
In addition, the acrylamide polymer material becomes a gel state insoluble in water at a temperature higher than the transition temperature, and becomes opaque, that is, a state where the transmittance of visible light is lowered. Below the transition temperature, it becomes a sol by dissolving in water or highly swollen, allowing visible light to pass through, and becoming transparent. Application to light-modulating materials and light-shielding materials using this phenomenon has also been studied (for example, Patent Documents 5 to 7).
These polymer compounds can detect temperature and control light. When light is input as an external stimulus, it is possible to control the light according to the light, and it is possible to cause local metastasis due to straightness, remote operability, and the like.
It is already known that polyisopropylacrylamide polymers exhibiting a phase transition by such light can be achieved by copolymerizing isopropylacrylamide with photoreactive sites (Non-patent Document 1), and various azobenzene sites can be obtained. By using this substituent, a polymer with little dependency on the amount added can be synthesized (Non-patent Document 2). A method for recovering soluble substances such as metal ions using isopropylacrylamide polymer imparted with photoresponsiveness by copolymerization (Patent Document 8) and a cell culture substrate (Patent Document 9) that changes cell adhesion have been proposed. .

Since the polymer compound is uniformly dissolved in a solvent containing water as a main component at a specific temperature, the polymer compound can be deposited along the irradiated light beam by light irradiation to form a scatterer. From this feature, it can be expected to be used as a moving screen in a volume scanning type stereoscopic display element.
2. Description of the Related Art Conventionally, an optical display element that uses generation of a scatterer is known that uses a liquid crystal material. When performing stereoscopic display, it is necessary to perform three-dimensional display, and a large amount of expensive liquid crystal material is required. For this reason, it is not realistic to use a liquid crystal material.
In the case of using a polymer compound exhibiting optical phase transition, the concentration of the polymer compound solution to be used is about 0.1 wt%, and its function can be exhibited. It can be obtained at a lower cost than a display element. Therefore, it is expected that a photoresponsive optical element can be obtained by introducing a photoresponsive site into a polymer compound, but in an optical element obtained by introducing a photoresponsive site by copolymerization, the polymer chain is not broken. As the uniformity increases, the temperature range showing the transition increases, which leaves a problem as an optical element.

For this reason, it is a polymer compound having a site made of a photoresponsive compound, and this photoresponsive compound has the property of detecting light and depositing along the irradiated light to form a scatterer. Development of a polymer compound that forms an optical element is eagerly desired.
By completing a polymer compound having this characteristic, a display element capable of volume scanning type stereoscopic display using scattered light deposited along the irradiation light can be realized.
Japanese Patent Application Laid-Open No. 7-228639 JP-A-9-169850 JP 2005-210936 A WO99 / 61904 Japanese Patent Publication No.61-7948 Japanese Patent Publication No. 1-38841 JP-A-5-181169 JP 2005-103534 A Japanese Patent Publication No. 2006-8975 D. Kungwachakun, M. Irie, Makromol Chem Rapid Commun, 9, 243 (1988). Yoshihisa Akiyama, Nobuyuki Tamaki, Journal of Polymer Science Part A-Polymer Chemistry, 42, 5200-5214, 2004

  An object of the present invention is a polymer compound having a site composed of a photoresponsive compound, the photoresponsive compound detects light, undergoes a phase transition in water at a lower critical solution temperature, and follows an irradiation light beam. A polymer compound having the property of forming a scatterer by precipitation and an optical material capable of reversibly taking a transparent-scattering state by irradiating light, and a display element including the optical material. It is an object of the present invention to provide a display element capable of volume scanning type stereoscopic display using scattered light deposited along the line.

The inventor diligently researched to solve the above-mentioned problems, and found the following to complete the present invention.
An atom transfer radical polymerization method has been developed as a method for easily producing a polymer compound with a controlled chemical structure. This method is a method in which the growth terminal of radical polymerization is capped with a halogen to be slowly polymerized while being protected (Review Paper: K. Matyjaszewski, J. Xia. Chem. Rev., 101, 2921-2990, 2001).
The present inventors can introduce a photoreactive site by the above-mentioned method using a polymerization initiator having a photoreactive site at the terminal or central part of a polymer compound exhibiting a lower critical solution temperature in water. I found.
In a solution composed of a high molecular compound obtained by this method, when a photoresponsive site is introduced by copolymerization, the non-uniformity of the polymer chain increases, so that the temperature range showing the transition is widened, which is a problem as an optical element. Unlike the conventional knowledge that resulted in leaving a point, the photoresponsive portion of the polymer compound detects light, causes a phase transition in water at the lower critical solution temperature, precipitates along the irradiated light, and scatters It was found that the body can be formed quickly.
When a photoreactive site is introduced using the above atom transfer radical polymerization method, light can be detected to cause a phase transition in water at a lower critical solution temperature, and precipitate along the irradiated light to form a scatterer. This means that only one unit in the polymer chain changes the properties of the entire polymer chain.
The present invention is a result obtained by finding such a revolutionary phenomenon.

According to the present invention, the following inventions are provided.
(1) A polymer compound having a photoreactive site at the end of a polymer exhibiting a lower critical solution temperature in water.
(2) A polymer compound having a photoreactive site in the center of a polymer exhibiting a lower critical solution temperature in water.
(3) The polymer exhibiting the lower critical solution temperature in water is composed of N-isopropylacrylamide, N, N-dimethylacrylamide, acrylate having an oxyethylene side chain, methacrylate having an oxyethylene group, and oxyethylene side. The polymer compound according to any one of (1) and (2), which is obtained by polymerizing a monomer selected from styrene having a chain. (4) The monomer constituting the polymer is N -Isopropylacrylamide or N, N-dimethylacrylamide, which consists of a copolymer of methacrylic acid, acrylic acid, methacrylic acid or alkyl ester of acrylic acid, acrylonitrile, acrylamide or a plurality of monomers in these ( The polymer compound according to 1) or (2).
(5) The polymer compound according to (1) or (2), wherein the photoreactive site comprises any one of azobenzene, chrysoidine, spiropyran, spirooxazine, diarylethene, chalcone, cinnamic acid ester, fulgide and leuco dye.
(6) An optical material comprising a solution of the polymer compound according to any one of (1) to (5) and capable of reversibly taking a transparent-scattering state when irradiated with light.
(7) A display element comprising the optical material according to (6).

The polymer compound of the present invention relates to a polymer having one photoreactive site at the end or center of the polymer exhibiting a lower critical solution temperature in water. It has the feature of causing a phase transition abruptly after absorbing light. More specifically, it is a polymer compound having a photoreactive site at the terminal or the center, and is uniformly dissolved in a solvent containing water as a main component. The present invention relates to a polymer compound having the property that is formed. Since this polymer is synthesized from a polymerization initiator having a photoreactive site, one photoreactive site always exists in one polymer chain, and the introduction position is defined as the terminal or the center. There is no structural heterogeneity and a sharp transition.
A display element such as a volume scanning type three-dimensional display or an optical shutter containing the optical material comprising the compound of the present invention can be obtained.

The present invention has a polymer compound having a photoreactive site at the end of a polymer compound exhibiting a lower critical solution temperature in water and a photoreactive site in the center of a polymer compound exhibiting a lower critical solution temperature in water It is a polymer compound.
The reverse end of the polymer compound having a photoreactive site at the terminal part or both ends of the polymer compound having a photoreactive site at the center part of the polymer compound having a photoreactive site are similar to the general radical polymerization termination reaction. It is considered to have a structure brought about by abstraction, addition of a hydroxyl group, coupling between radicals, elimination reaction, and the like. For example, from the results of mass spectrometry of polymers synthesized by atom transfer polymerization, adducts of hydroxyl groups, lactone structures formed by elimination of chlorine and hydrolysis of amides, or structures in which terminal chlorine is considered to have simply been eliminated upon ionization Has been observed.

A polymer compound exhibiting a lower critical solution temperature in water means a polymer compound that has a function of causing a phase transition in water at a lower critical solution temperature and precipitating along an irradiation beam to form a scatterer. .
The above-mentioned “polymer compound exhibiting a lower critical solution temperature in water” means that the monomers are N-isopropylacrylamide, N, N-dimethylacrylamide, acrylate having an oxyethylene side chain, methacrylate having an oxyethylene group, oxyethylene side It is obtained by polymerizing a monomer selected from styrene having a chain.
The monomer constituting the polymer is N-isopropylacrylamide or N, N-dimethylacrylamide, and any of methacrylic acid, acrylic acid, methacrylic acid or alkyl ester of acrylic acid, acrylonitrile, acrylamide A polymer compound composed of a copolymer composed of a plurality of monomers can also be used.
The alkyl ester has C1-C8 carbon atoms. Alkyl may be linear or branched.

A compound constituting a photoreactive site is introduced into the terminal portion or the central portion of the “polymer compound exhibiting the lower critical solution temperature in water”.
The compound constituting the photoreactive site is obtained by reacting a polymer compound exhibiting the lower critical solution temperature in water with the compound constituting the photoreactive site being used as a polymerization initiator, thereby reducing the lower critical solution temperature in water. It can introduce | transduce into the terminal part or center part of the high molecular compound shown.

The compound constituting the photoreactive site is any one of azobenzene, chrysidine, spiropyran, spirooxazine, diarylethene, chalcone, cinnamic ester, fulgide and leuco dye, and all of them undergo reversible photoisomerization reaction. Show.
For example, when p-hydroxyazobenzene, which is a derivative of azobenzene, is reacted with 2-chloropropionic acid chloride, the desired polymerization initiator is obtained.
This compound may be introduced as a single compound, or can be introduced as a multimer such as a dimer or a trimer, but when it is incorporated as a monomer or dimer, non-uniformity appears. It is not preferable. A reaction method in which non-uniformity does not occur is conceivable, but it is considered that good results can be obtained if it is incorporated in the start reaction or in the future in the stop reaction.

Using a compound constituting the photoreactive site as a polymerization initiator, a monomer that forms the “polymer compound exhibiting the lower critical solution temperature in water” is reacted. In the case of one initiation reaction point, the polymer chain grows in one direction from the initiator containing the photoreactive site, so the photoreactive group enters the end, and in the case of two places it grows on both sides, so it is introduced in the center. Is done. In the case of radical polymerization from an initiator having two starting points, two growing ends are always present close to each other, and the growing ends cause a coupling reaction to stop the reaction. Therefore, in this case, the atom transfer polymerization method is used in particular, and the polymerization is slowly carried out while capping and protecting the growth terminal of radical polymerization with halogen.
As a solvent, water, dimethylformamide, alcohol or the like is used, and a photoreactive initiator, for example, 2-chloropropionic acid phenylazophenyl ester and the monomer N-isopropylacrylamide are added thereto, and the solvent is replaced with an inert gas. Degas oxygen.
To this, a polyvalent amine of monovalent copper halide (for example, tri [2- (N, N-dimethylamino) ethyl] amine, alkylbipyridine, pentamethyldiethylenetriamine) complex is added, and the temperature is from room temperature to 40 ° C. for 1 hour. 24 hours later, the reaction is stopped, and the solution containing the reaction product is passed through an alumina gel to remove the polyvalent amine complex (copper complex) of the monovalent copper halide.
Thereafter, reprecipitation is performed with ethyl ether. Instead of the reprecipitation operation, silica gel column chromatography may be performed using a mixed solvent of ethyl acetate and methanol as a developing solvent.
By this operation, a polymer compound having a photoreactive site at a terminal portion of a polymer compound exhibiting a lower critical solution temperature in water as a target substance and a photoreaction in a central portion of the polymer compound exhibiting a lower critical solution temperature in water. It is possible to obtain a polymer compound having a sex site.

The weight average molecular weight of the polymer compound obtained as described above is in the range of 1000 to 100,000. The structure of the polymer compound can be confirmed by nuclear magnetic resonance spectroscopy and matrix-assisted laser desorption / ionization mass spectrometry.
Since this polymer is synthesized from a polymerization initiator having a photoreactive site, one photoreactive site always exists in one polymer chain, and the introduction position is defined as the terminal or the center. It is characterized by sharp transition without structural non-uniformity.
Conventional examples of such polymers include initiators having spirooxazine (Macromolecules 2004, 37, 9664-9666) and azobenzene (Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 43, 2358-2367, 2005) groups. However, in this case, it is insoluble in water and does not show the lower critical solution temperature.

It is a polymer compound that has the characteristics that this photoresponsive compound detects light of a specific wavelength, undergoes a phase transition in water at the lower critical solution temperature, precipitates along the irradiated light, and forms a scatterer. I can confirm that there is.
An optical material containing this polymer compound can reversibly take a transparent-scattering state when irradiated with light, and can be used as an optical material using this property.
In a display element including this optical material, a display element capable of volume scanning type stereoscopic display using scattered light deposited along an irradiation light beam that can reversibly take a transparent-scattering state when irradiated with light. Available as

Synthesis Method of Polymerization Initiator A (Compound Represented by Structural Formula (1)) 0.5 g of p-hydroxyazobenzene was dissolved in 10 ml of dehydrated dichloromethane, 0.26 g of triethylamine was added, and 0.32 g of 2-chloropropionic acid chloride was added thereto. Add slowly. The mixed solution was stirred at room temperature for 1 hour, hexane was added, the precipitate was filtered, the filtrate was concentrated, and column chromatography separation was performed using hexane: dichloromethane (1: 1) as a developing solvent. 0.45 g of the target compound was obtained.

Synthesis method of polymerization initiator B (compound represented by structural formula (2))
Dissolve 0.90 g of p, p'-dihydroxyazobenzene in 30 ml of dehydrated dichloromethane, add 0.90 g of triethylamine, and slowly add 1.1 g of 2-chloropropionic acid chloride. The mixed solution was stirred at room temperature for 1 hour and then concentrated to perform column chromatography separation using dichloromethane as a developing solvent. 0.89 g of the target compound was obtained.

Synthesis Method of Polymerization Initiator C (Compound Represented by Structural Formula (3)) 0.62 g of p-aminoazobenzene was dissolved in 50 ml of dehydrated dichloromethane, 0.32 g of triethylamine was added, and 0.40 g of 2-chloropropionic acid chloride was added thereto. Add slowly. The mixed solution was stirred at room temperature for 1 hour, then concentrated and subjected to column chromatography separation using dichloromethane as a developing solvent. 0.78 g of the target compound was obtained.

Synthesis method of polymerization initiator D (compound represented by structural formula (4)) Dissolve 1.0 g of chrysoidine in 50 ml of dehydrated dichloromethane, add 1.3 g of triethylamine, and slowly add 1.1 g of 2-chloropropionic acid chloride thereto. Add. The mixed solution was stirred at room temperature for 2 hours, then concentrated and subjected to column chromatography separation using ethyl acetate and dichloromethane (1: 9) as developing solvents. 1.0 g of the target compound was obtained.

Regarding the polymerization method, 17.3 mg of polymerization initiator A and 340 mg of N-isopropylacrylamide were dissolved in 1.2 ml of dimethylformamide (DMF) and replaced with dry nitrogen gas. 12 mg of cuprous chloride and 33 ml of tri (2- (dimethylamino) ethyl) amine are dissolved in 0.3 g of pure water under a nitrogen atmosphere and added to the previous solution. The mixture was stirred at room temperature for 24 hours, diluted with THF, and passed through an alumina column. After concentration, reprecipitation purification was performed twice with ethyl ether to obtain 150 mg of polymer compound A. When the degree of polymerization was determined by measuring NMR, it was a 42-mer. Moreover, the weight average molecular weight was 4900 in the measurement of MALDI-MS.

Polymerization initiator B 23.7 mg and N-isopropylacrylamide 680 mg were dissolved in 6 ml of dimethylformamide (DMF) and replaced with dry nitrogen gas. 12 mg of cuprous chloride and 33 ml of tri (2- (dimethylamino) ethyl) amine were dissolved in 0.5 g of pure water under a nitrogen atmosphere and added to the previous solution. After stirring at 28 ° C. for 24 hours, it was diluted with THF and passed through an alumina column. After concentration, reprecipitation purification was performed twice with ethyl ether to obtain 200 mg of polymer compound B. When the degree of polymerization was determined by measuring NMR, it was 56-mer. In addition, the weight average molecular weight was 4800 as measured by MALDI-MS.

Polymerization initiator C 34.6 mg and N-isopropylacrylamide 680 mg were dissolved in dimethylformamide DMF 1.5 ml and replaced with dry nitrogen gas. Cuprous chloride (24 mg) and tri (2- (dimethylamino) ethyl) amine (33 ml) were dissolved in 0.35 g of pure water under a nitrogen atmosphere and added to the previous solution. After stirring at 40 ° C. for 2 hours, the mixture was diluted with ethyl acetate and purified by passing through a silica gel column to obtain 200 mg of polymer compound C. When the degree of polymerization was determined by measuring NMR, it was a 30-mer.

Polymerization initiator D (47.4 mg) and N-isopropylacrylamide (680 mg) were dissolved in dimethylformamide (DMF) (1.5 ml) and replaced with dry nitrogen gas. Cuprous chloride (48 mg) and tri (2- (dimethylamino) ethyl) amine (66 ml) were dissolved in 0.37 g of pure water under a nitrogen atmosphere and added to the previous solution. After stirring at 40 ° C. for 2 hours, the mixture was diluted with ethyl acetate and purified by passing through a silica gel column to obtain 70 mg of polymer compound D. When the degree of polymerization was determined by measuring NMR, it was an 11-mer.

Measurement of phase transition temperature and measurement of light transmittance change The synthesized polymer compound A is dissolved in pure water so that the concentration becomes 0.1 wt%, and this is put into a 1 cm square quartz cell, and a temperature control cell holder is used. The transmittance was measured while changing the temperature. Next, the transmittance was measured while irradiating this solution with light of 365 nm and similarly changing the temperature. The results are shown in FIG. 1 and FIG. FIG. 1 is a graph showing the change in transmittance with temperature in a 0.1 wt% aqueous solution of polymer compound A. FIG. A solid line indicates a state before light irradiation, and a dotted line indicates a state after ultraviolet irradiation. FIG. 2 shows the change in transmittance with temperature in a 0.1 wt% aqueous solution of polymer compound B. The solid line is the result after visible light irradiation, and the dotted line is the result after ultraviolet irradiation.
From the above results, the photoresponsive compound detects light of a specific wavelength, causes a phase transition in water at the lower critical solution temperature, and precipitates along the irradiated light to form a scatterer. A high-molecular compound having an optical material capable of reversibly taking a transparent-scattering state by irradiation with light, and a display element including the optical material, and volume scanning using scattered light deposited along the irradiation light It was confirmed that it can be used as a display element capable of three-dimensional display of molds.

FIG. 6 is a graph showing a change in transmittance with temperature in a 0.1 wt% aqueous solution of polymer A. The transmittance change with temperature in a 0.1 wt% aqueous solution of polymer B is shown.

Claims (5)

The lower critical solution temperature in water, and the monomer is N-isopropylacrylamide, N, N-dimethylacrylamide, acrylate having oxyethylene side chain, methacrylate having oxyethylene group, styrene having oxyethylene side chain At the end of the polymer having a weight average molecular weight in the range of 1000 to 100,000 , the azobenzene, chrysidine, spiropyran, spirooxazine, diarylethene, chalcone, cinnamic acid ester, fulgide and leuco are obtained by polymerizing selected monomers. A polymer compound having a photoreactive site comprising any one compound of a dye . The lower critical solution temperature in water, and the monomer is N-isopropylacrylamide, N, N-dimethylacrylamide, acrylate having oxyethylene side chain, methacrylate having oxyethylene group, styrene having oxyethylene side chain At the center of the polymer obtained by polymerizing selected monomers and having a weight average molecular weight in the range of 1000 to 100,000 , azobenzene, chrysidine, spiropyran, spirooxazine, diarylethene, chalcone, cinnamic acid ester, fulgide and leuco A polymer compound having a photoreactive site comprising any one compound of a dye . The monomer constituting the polymer is N-isopropylacrylamide or N, N-dimethylacrylamide, and one of methacrylic acid, acrylic acid, methacrylic acid or alkyl ester of acrylic acid, acrylonitrile, acrylamide, or a plurality of these The polymer compound according to claim 1 or 2, comprising a copolymer comprising monomers. Optical material characterized by that can take reversibly scattering state - made from a solution of claims 1 to 3 polymer compound according any, transparent by irradiating light. A display element comprising the optical material according to claim 4 .

Images