JPH064654B2 - Cumulative film and cumulative polymerized film and methods for producing the same - Google Patents

Description

TECHNICAL FIELD The present invention relates to a cumulative film and a cumulative polymerized film of a compound having a phospholipid-like structure, and a method for producing them.

(Prior Art) Various phospholipids are contained in the living body, and it has been clarified that these phospholipids play an important role for maintaining the life of the living body.

For example, phospholipids are cytoplasmic components such as cell membranes,
It is closely related to various metabolic processes in the living body, and in addition,
It also plays a very important role in the energy source of brain tissue, the transportation and absorption of fat, the coagulation of blood, and the perception of the taste of food.

As described above, since phospholipids have many functions in supporting life as a whole, many attempts have been made to apply them to various artificial organs, cell fusion, enzyme immobilization, artificial cultivation, biosensors and the like.

Therefore, the humidity sensor, gas sensor, ion permeable membrane, artificial organ, cell fusion, enzyme fixation, biosensor,
In order to use them in fields such as artificial cultivation, there is a great demand for them to be obtained with a relatively high polymer and to be capable of forming a strong film, and to have high economic efficiency.

On the other hand, in living tissues, molecules form a highly ordered system, and some molecules constitute a functional unit and emphasize the action (Reference: “Surface Science” Vol.6, No.2, 1985-6-1,
Pages 16-29). In other words, it expresses the characteristic peculiar to the molecular sequence. Recently, ultra-thin films in which monolayers are accumulated have attracted attention as a method of expressing various functions of organic molecules, and in particular, monolayer accumulation films and their fabrication technology are indispensable for realizing molecular electronic devices, bioelectronic devices, etc. It is said that.

(Problems to be Solved by the Invention) However, also in the case of a phospholipid-like compound, the expression of a new function and the conventionally known property can be improved by accumulating its monomolecular film, that is, forming an ultrathin film. However, the formation of these artificial cumulative films has not been realized yet.

An object of the present invention is to provide a monomolecular cumulative membrane of molecules having a phospholipid-like structure, a cumulative polymeric membrane in which the strength is improved by polymerizing the same, and a method for producing them.

(Means for Solving Problems) The present invention solves the above problems, and the first invention is the following general formula: (R in the formula represents —H or —CH ₃ ). The present invention relates to a cumulative film comprising a plurality of monomolecular layers of a compound having a phospholipid-like structure represented by the formula:

The compound having a phospholipid-like structure in which R is a hydrogen atom (H) in the above formula (I) is a compound in which D-α-phosphatidylethanolaminedipalmitoyl or L-α-phosphatidylethanolaminedipalmitoyl is triethylamine and pyridine or tetrahydrofuran ( THF)
It can be produced by reacting with acrylic acid chloride in the presence.

Further, in the formula (I), a compound having a phospholipid-like structure in which R is a methyl group (—CH ₃ ) can be prepared by converting D-α-phosphatidylethanolamine dipalmitoyl or L-α-phosphatidylethanolamine dipalmitoyl into triethylamine and pyridine or Tetrahydrofuran (T
It can be produced by reacting with methacrylic acid chloride in the presence of HF).

Next, the second invention of the present invention has the following general formula: (In the formula, R represents —H or —CH ₃ , and z represents the degree of polymerization.)
The present invention relates to a cumulative polymer film characterized by comprising a plurality of laminated monomolecular layers of a polymer having a phospholipid-like structure represented by.

The polymer represented by the above formula (II) is obtained by irradiating the compound represented by the formula (I) with high-energy radiation such as γ-rays, x-rays, electron beams and ultraviolet rays to polymerize the compound.

Next, a third invention of the present invention relates to a method for producing a cumulative membrane of the first invention, which comprises forming a monomolecular layer of a compound having a phospholipid-like structure represented by the formula (I) on the water surface. And the monomolecular layers are laminated one by one on a solid substrate.

Furthermore, a fourth invention of the present invention relates to a method for producing a cumulatively polymerized membrane of the second invention, which comprises forming a monomolecular layer of a compound having a phospholipid-like structure represented by the formula (I) on the water surface. It is characterized in that a monomolecular cumulative film of the compound of the formula (I) is formed by laminating the monomolecular layers one by one on a solid substrate, and the monomolecular cumulative film is irradiated with radiation.

As the solid substrate used in the third and fourth inventions, there are plastics substrates such as polyethylene terephthalate, glass substrates, silicon substrates and the like.

(Operation) The Langmuir-Blodgett method (LB method) is known as an effective method for producing a cumulative film. The details of this method are described in the above-mentioned document, and the main points are as follows.

When a molecule having a hydrophilic group and an elongated hydrophobic group in the same molecule is floated on the water surface and an appropriate pressure is applied from the lateral direction, this molecule forms a monomolecular film in which the hydrophilic groups contact the water surface and are regularly arranged. . By dipping and pulling up the solid substrate in this monomolecular film, the monomolecular film adheres to the substrate. Further, by repeating this operation, a monomolecular cumulative film can be obtained.

It is known that three types of X-type, Y-type and Z-type are present in this cumulative film depending on the properties of the molecule and the substrate.

FIGS. 1 (A) to (C) schematically show these, and in the case of FIG. 1 (A), when the substrate 1 is immersed, the molecules on the water surface 4 have their hydrophobic groups 2 attached to the substrate. It attaches toward the side, but when pulling up the substrate, no molecules attach. By repeating this operation, a cumulative film as shown in FIG. 1 (A) is obtained. This is called an X-type cumulative film. In the case of FIG. 1 (B), when the substrate is pulled up, the hydrophilic group 3 of the molecule contacts and adheres to the substrate, and when immersed, the hydrophobic group 2 of the molecule floating on the water surface 4 is already attached to the substrate. Attaches in contact with the hydrophobic group of the attached molecule. When this operation is repeated, the molecules are accumulated as-head-tail-tail-head-head-tail-tail-head. This is called a Y-type cumulative film. In the case of FIG. 1 (C), when the substrate 1 is pulled up, the molecules on the water surface are attached with their hydrophilic groups 3 facing the substrate side, but they are not attached when the substrate is immersed. The accumulation in this case is called Z type.

As explained above, whether or not a cumulative film can be obtained by the LB method and which type of film is obtained depend on the balance of hydrophobic and hydrophilic groups in the molecule, pH of water, temperature, etc. To do.
Therefore, it is not easy to find the molecules and conditions that form the cumulative film.

According to the present invention, since the compound having the phospholipid-like structure represented by the formula (I) is used, a good cumulative film can be obtained by the LB method, and the cumulative film can be polymerized by irradiation with radiation. Therefore, the strength of the film can be improved.

(Examples) The present invention will be described with reference to the following reference examples and examples.

Reference Example 1 As shown in the following reaction formula (A), 0.1 mol of commercially available D-α-phosphatidylethanolamine dipalmitoyl (compound V), which is one of natural phospholipids, was added to 200c.
It was dissolved in m ³ of pyridine, triethylamine in an amount twice that of Compound V was added, and the mixture was cooled with ice. To this, 2.5 times mol of acrylic acid chloride was gradually added and reacted. After the reaction, the precipitated triethylamine hydrochloride was filtered with a filter, the mother liquor was concentrated, and the precipitated solid was ice-cooled.
-Washed with hexane and further purified by chromatography.
The yield of this product was about 40%.

This product was dissolved in CDC ₃ and the ¹ H-NMR spectrum was measured. As a result, from the ¹ H chemical shift value (δ),
The following groups were confirmed. δ = 0.93 ppm (-CH ₃ ),
1.25ppm _(-CH 2 -), 2.10~2.20ppm
_{(-CO-CH 2 -),} 3.70~4.25ppm (-O
^{_{CH 2 -); (- N}} + CH 2); (-CONH-), 5.25 to 5.28 ppm (-CH
=); 5.60 ppm (-CH =). Further, from the infrared absorption spectrum, CONH (1660 cm ⁻¹ ) and> C = C <
(1640 cm ^-1 ) was confirmed. From these results,
It was confirmed that the product was the compound III produced in the reaction of the reaction formula (A).

The compound thus obtained was dissolved in benzene, applied on a silicon substrate and then dried to form a film. The γ-rays generated from a ⁶⁰ Co in the coating dose 82 Mrad (M
When irradiated with rad), it changed into a strong white elastic film. As a result of measuring an infrared absorption spectrum of this film, a wave number of 1640 corresponding to a vinyl group (H ₂ C = CH-) was obtained.
It was confirmed that the absorption at cm ^-1 almost disappeared and the other absorptions were almost completely retained. In addition, this film became insoluble in benzene which is a solvent of the monomer.

Reference Example 2 Methacrylic acid chloride was used as a starting material and compound V was reacted under the same conditions as in Reference Example 1 except that the product was analyzed. As a result, the product was produced by the reaction of the following reaction formula (B). It was confirmed to be compound IV.

Similar results were obtained when tetrahydrofuran (THF) was used instead of pyridine in this reaction.

When the compound IV thus obtained was subjected to radiation polymerization in the same manner as in Reference Example 1, a strong polymer film having elasticity was obtained.

Reference Example 3 When an optical isomer of compound V, that is, L-α-phosphatidylethanolaminedipalmitoyl was used as a raw material and the same reaction as in Reference Examples 1 and 2 was performed, the same reaction as in Reference Examples 1 and 2 was performed. Polymeric membranes with strong elastic phospholipid-like structure were obtained.

Example 1 50 mg of the compound III having the phospholipid-like structure was added to 5c.
It is dissolved in m ³ of benzene, and an appropriate amount of this is dropped on a water tray (20 ° C) of a Lauda LB film forming apparatus, left to stand for a while to evaporate benzene, and then the surface area of the water surface is reduced by a barrier. A monolayer of compound III was formed on top. The surface pressure at this time was set to 37 dyn / cm. Next, when a cleanly washed polyethylene terephthalate substrate was immersed and pulled up, the occupied area of the monolayer on the water surface decreased only when the substrate was pulled up, and when the substrate was immersed, the monolayer occupied. The area did not change. Ie compound
III has been found to give a Z-type cumulative film. 2 mm
As a result of repeating the dipping and pulling operations at a speed of / minute, compound III could be accumulated up to about 60 layers.

Example 2 Next, when the cumulative film obtained in Example 1 was irradiated with γ-rays generated from ⁶⁰ Co at an irradiation dose of 82 megarads (Mrad), the film changed to a white elastic film. As a result of measuring the infrared absorption spectrum of this film, it was confirmed that the absorption at a wave number of 1640 cm ⁻¹ corresponding to a vinyl group (H ₂ C═CH—) almost disappeared and the other absorptions were almost completely retained. Was given. In addition, this film became insoluble in benzene which is a solvent for the monomer. That is, it was confirmed that the cumulative film of the compound III (monomer) was vinyl-polymerized by irradiation with γ-ray to give a strong cumulative polymer film having elasticity.

Example 3 Next, when a cumulative glass film was formed using a clean glass substrate and a silicon substrate having a hydrophilic surface, the same results as above were obtained.

Example 4 A cumulative film was formed in the same manner as in Example 1 using the compound IV having the phospholipid-like structure, and the number of layers was about 50.
It was confirmed that a Z-type cumulative film of layers could be formed. Further, a cumulative polymerized film was obtained by irradiating the cumulative film with γ-rays in the same manner as in Example 2.

(Effect of the invention) As described in detail above, according to the present invention, a cumulative film of molecules having a structure extremely close to that of natural phospholipid can be obtained, and the cumulative film is polymerized by the radiation polymerization method to increase the strength of the film. Can be strengthened. Therefore, this membrane can be applied to a wide range of fields such as humidity sensors, gas sensors, ion-permeable membranes, artificial organs, cell fusion, enzyme immobilization, biosensors, and artificial cultivation, and its industrial value is very large.

[Brief description of drawings]

FIGS. 1 (A) to 1 (C) are explanatory views of the accumulation of molecules in the LB method. 1 ... Substrate, 2 ... Hydrophobic group, 3 ... Hydrophilic group, 4 ... Water surface.

Claims (4)

[Claims] 1. The following general formula A cumulative film comprising a plurality of monomolecular layers of a compound having a phospholipid-like structure represented by (R in the formula represents —H or —CH ₃ ). 2. The following general formula (In the formula, R represents —H or —CH ₃ , and z represents the degree of polymerization.)
A cumulative polymer film comprising a plurality of monolayers of a polymer having a phospholipid-like structure represented by 3. The following general formula Forming a monomolecular layer of a compound having a phospholipid-like structure represented by (R in the formula represents —H or —CH ₃ ) on the water surface, and laminating the monomolecular layers one by one on a solid substrate A method for producing a cumulative film, comprising: 4. The following general formula Forming a monomolecular layer of a compound having a phospholipid-like structure represented by (R in the formula represents —H or —CH ₃ ) on the water surface, and laminating the monomolecular layers one by one on a solid substrate A monomolecular cumulative film of the above compound is formed according to the above, and the monomolecular cumulative film is irradiated with radiation.