JP5062737B2 - Method for producing hollow fiber organic nanotube - Google Patents

Description

  The present invention relates to hollow fibrous organic nanotubes useful as inclusion / separation materials, drug sustained-release materials, or high-functional materials in the fields of medicine and chemicals, and more particularly to alkaline aqueous solutions. The present invention relates to a method for easily producing hollow fiber organic nanotubes by adding an acidic compound after dissolution, or adding an alkaline compound after dissolution in an acidic aqueous solution.

As a material representative of nanotechnology, a nanotube-like material having pores of 0.5 to 500 nanometers (hereinafter referred to as nm) has attracted attention. Among them, carbon nanotubes, which are inorganic nanotubes synthesized artificially for the first time, are well known (Non-Patent Document 1). From the expectation of characteristics derived from their size, shape, chemical structure, etc., nanoscale In addition to the development of applications for electronic devices, high-strength materials, electron emission, gas storage, etc., research on mass production has been actively pursued from the demand for practical application (Patent Document 1 and Non-Patent Document 2).
Clodextrin is famous as an organic cyclic compound having pores of 1 nm or less. Cyclodextrins can encapsulate various low-molecular-weight organic compounds in the annular hollow part, so that they can be used in various ways for the purpose of contributing to the health food field, cosmetics field, antibacterial deodorization / household goods field, industry / agriculture / environment field. Many cyclodextrin inclusion products have been researched and developed and have already been commercialized (Patent Document 2, Patent Document 3, Patent Document 4). The development of a wide range of applications for such cyclodextrins is realized by the mass production of cyclodextrins and the structure of cyclodextrins in which 6 to 8 units of glucose are linked in a ring, which is safe for the living body. The main factor is that it is secured.

  The inventors of the present invention are expected to be applied in fields different from inorganic nanotubes. In addition, glycolipids in which a sugar residue is bonded to a long-chain hydrocarbon group having a hollow structure having an inner pore size larger than that of cyclodextrin. It has succeeded in synthesizing hollow fiber-like organic nanotubes formed by self-assembly (Patent Document 5, Non-Patent Document 3). The hollow fiber-like organic nanotube has a hollow cylinder portion with an inner pore size of 5 to 500 nm, which is an order of magnitude larger than that of cyclodextrin. Therefore, inclusion of 5-500 nm protein, virus, There is a possibility that metal fine particles and other inorganic fine particles can be trapped inside the hollow cylinder, and development of their use is expected. In order to actively promote the development of new applications of such hollow fiber-like organic nanotubes, it is desirable to develop hollow fiber-like organic nanotubes using compounds other than the glycolipids and their synthesis methods.

Accordingly, the present inventors proceeded with the synthesis of hollow fiber-like organic nanotubes formed by self-assembly of peptide lipids in which the carboxyl group of long-chain fatty acid and the N-terminus of oligopeptide were bound. As a result, it has been found that a nano-sized hollow fibrous structure is formed by allowing a peptide lipid and a transition metal to coexist in water (Patent Document 6).
However, a method for directly synthesizing hollow fiber organic nanotubes from peptide lipids in which the carboxyl group of a long-chain fatty acid and the N-terminus of an oligopeptide are bonded without using a transition metal, and the hollow fiber organic nanotubes have been known so far. I couldn't.
In addition, since this peptide lipid has a carboxyl group at the end of the molecule, it has a drawback that it is stable under acidic conditions but unstable under alkaline conditions. A method for directly synthesizing hollow fiber organic nanotubes from peptide lipids in which the amino group of a long-chain amine expected to solve this problem and the C-terminus of the oligopeptide are combined, and the hollow fiber organic nanotubes have so far been unknown.
Special table 2003-535794 gazette JP 2005-306763 A JP 2006-1917 A JP-A-7-109254 JP 2004-224717 A JP 2004-250797 A S.Iijima, Nature, 1991, 354, 56 K.Hata, DonN.Futaba, K.Mizuno, T.Namai, M.Yumura, S.Iijima, Science, 2004, 306, 1362 S. Kamiya, H. Minamikawa, JHJung, Y.Bo, M. Masuda, T. Shimizu, Langmuir, 2005, 21, 743 B. Yang, S. Kamiya, K. Yoshida, T. Shimizu, Chem. Comm., 2004, 500 B. Yang, S. Kamiya, N. Koshizaki, Y. Shimizu, T. Shimizu, Chem. Mater., 2004, 16, 2826

  The present invention provides a hollow fiber-like organic nanotube that has characteristics not found in inorganic nanotubes typified by carbon nanotubes and that has an inner diameter and a high axial ratio that are about 10 times larger than that of cyclodextrin without using a transition metal. It is an object to provide a method that can be synthesized.

  As a result of intensive studies to solve the above-mentioned problems, the inventors have dissolved peptide lipids composed of long-chain hydrocarbon group and peptide chain conjugates in an alkaline aqueous solution and then added an acidic compound, or dissolved in an acidic aqueous solution. After that, when self-assembly was performed by adding an alkaline compound, a nano-sized hollow fiber-like structure was formed without using a transition metal, and the present invention was completed.

That is, the present invention provides the following general formula (1)
RCO (NH—CHR′—CO) _m OH (1)
(Wherein R represents a hydrocarbon group having 6 to 24 carbon atoms, R ′ represents an amino acid side chain, m represents 2 or 3 ), a step of dissolving the peptide lipid in an alkaline aqueous solution, and the solution is acidic A method for producing hollow fiber organic nanotubes, comprising a step of leaving in an atmosphere and a step of recovering hollow fiber organic nanotubes produced by self-assembly in a solution from a solution and air drying or drying under reduced pressure at room temperature. is there.
Further, the present invention provides the following general formula (2)
H (NH—CHR′—CO) _m NHR (2)
(Wherein R represents a hydrocarbon group having 6 to 24 carbon atoms, R ′ represents an amino acid side chain, m represents 2 or 3 ), a step of dissolving the peptide lipid in an acidic aqueous solution, and the solution in an alkaline atmosphere A method for producing hollow fiber organic nanotubes, comprising: a step of leaving the substrate under a vacuum; and a step of recovering hollow fiber-like organic nanotubes generated by self-assembly in a solution from a solution and air-drying or drying under reduced pressure at room temperature. .

According to the present invention, the following general formula (1)
RCO (NH—CHR′—CO) _m OH (1)
(Wherein R represents a hydrocarbon group having 6 to 24 carbon atoms, R ′ represents an amino acid side chain, and m represents 2 or 3 ) or the following general formula (2)
H (NH—CHR′—CO) _m NHR (2)
(Wherein R represents a hydrocarbon group having 6 to 24 carbon atoms, R ′ represents an amino acid side chain, and m represents 2 or 3 ), a hollow fiber structure suitable for practical use, comprising a peptide lipid, A hollow fiber-like organic nanotube having a shape can be easily produced without using a transition metal.

The peptide lipid of the present invention is a peptide lipid having a long-chain hydrocarbon group, that is, the following general formula (1)
RCO (NH—CHR′—CO) _m OH (1)
Or the following general formula (2)
H (NH—CHR′—CO) _m NHR (2)
A hollow fiber-like organic nanotube can be produced using this as a raw material.

In the general formula (1) and the general formula (2), R is a hydrocarbon group having 6 to 24 carbon atoms, preferably a linear hydrocarbon which may have a side chain having 2 or less carbon atoms. This hydrocarbon group may be saturated or unsaturated. In the case of unsaturated, it is preferable to contain 3 or less double bonds. R has 6 to 24 carbon atoms, preferably 10 to 16 carbon atoms. Such hydrocarbon groups include hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl , Eicosyl group, heneicosyl group, docosyl group, tricosyl group, tetracosyl group, pentacosyl group, hexacosyl group and the like.
In the general formulas (1) and (2), R ′ is an amino acid side chain, and examples of the amino acid include glycine, valine, leucine, isoleucine, alanine, arginine, glutamine, lysine, and aspartic acid. , Glutamic acid, proline, cysteine, threonine, methionine, histidine, phenylalanine, tyrosine, tryptophan, asparagine, and serine, preferably glycine. This amino acid side chain may be any of D, L, and racemate, but naturally derived is usually L.
In the above general formula (1) and general formula (2), m is an integer of 1 to 10, preferably 2.

The method for producing the peptide lipid of the present invention is not particularly limited, but the peptide lipid represented by the general formula (1) is, for example, the general formula R-COOH (wherein R has the same meaning as R in the general formula (1)). A long chain carboxylic acid represented by the general formula R-COCl (wherein R has the same meaning as R in the general formula (1)), N-terminal side of the peptide It can be produced by reacting with to form a peptide bond.
As long chain carboxylic acids, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decane, undecanoic acid, dodecanoic acid, tridecanoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, heptadecanoic acid, octadecanoic acid, nonadecanoic acid, eicosanoic acid And heneicosanoic acid, docosanoic acid, tricosanoic acid, tetracosanoic acid, pentacosanoic acid and hexacosanoic acid. Of these, dodecanoic acid, tetradecanoic acid, and the like are desirable because of the balance of the amphipathic properties of the obtained peptide lipids and the fact that they are naturally available and are available at low cost.

The peptide lipid represented by the general formula (2) is, for example, a long chain amine represented by the general formula R-NH ₂ (wherein R has the same meaning as R in the general formula (2)), It can be produced by reacting with the C-terminal side of the peptide to form a peptide bond.
As long chain amines, hexylamine, heptylamine, octylamine, nonylamine, decylamine, undecylamine, dodecylamine, tridecylamine, tetradecylamine, pentadecylamine, hexadecylamine, heptadecylamine, octadecylamine, nonadecylamine, Examples include eicosylamine, heneicosylamine, docosylamine, tricosylamine, tetracosylamine, pentacosylamine, and hexacosylamine. Of these, tetradecylamine, hexadecylamine, and the like are desirable because of the balance of the amphiphilic properties of the obtained peptide lipids and the availability at low cost.
The N-terminus of the peptide lipid represented by the general formula (2) is usually isolated as an acid salt having a halogen atom. This is because the N-terminal is modified with various protecting groups to perform deprotection using various dilute acids / organic solvents. Furthermore, it is more chemically stable to store as an acid salt having a halogen atom than to store the N-terminal amino group in a free state. As the salt, hydrobromide, hydrochloride and the like are common, but in general, hydrochloride.

Next, a method for producing hollow fiber-like organic nanotubes using this peptide lipid will be described.
(1a) A peptide lipid represented by the general formula (1) RCO (NH—CHR′—CO) _m OH is dissolved in an alkaline aqueous solution to prepare a solution. Peptide lipids are dissolved in an alkaline aqueous solution to form a carboxylate anion at the end of the lipid. In preparing this solution, no particular heating is required. The higher the concentration of peptide lipid in this solution, the better and most preferably saturated. This alkaline aqueous solution is an aqueous solution such as an alkali metal hydroxide or alkaline earth metal hydroxide, or a buffer solution having a pH of 7 or more, and preferably has a pH in the range of 7.5 to 12.
Examples of the alkali metal hydroxide include sodium hydroxide, lithium hydroxide, and potassium hydroxide.
Examples of the alkaline earth metal hydroxide include magnesium hydroxide, calcium hydroxide, and barium hydroxide.
Examples of the buffer solution having a pH of 7 or higher include aqueous solutions of borate, carbonate, ammonium salt and the like.

Next, the acidic compound is directly diluted in this solution, preferably with water, as a dilute acidic aqueous solution of 5 wt% or less, more preferably as 1 wt% or less of dilute acidic aqueous solution, even more preferably 1 wt% or less. Add by vapor diffusion of a dilute acidic aqueous solution.
Examples of the acidic compound include hydrochloric acid, sulfuric acid, nitric acid, and hydrobromic acid. Furthermore, you may use the mixed solution which mixed 2 or more types of these acidic compounds.
As a result, the carboxylate anion formed at the end of the peptide lipid is neutralized by protons derived from acidic compounds to become carboxylic acid, and depending on the decrease in solubility in aqueous solution, hollow fibrous substances precipitate from the solution. come.

(1b) As another method, a peptide lipid represented by the general formula (2) H (NH—CHR′—CO) _m NHR is dissolved in an acidic aqueous solution to prepare a solution. Peptide lipids dissolve in an acidic aqueous solution to form ammonium cations at the lipid ends. In preparing this solution, no particular heating is required. The higher the concentration of peptide lipid in this solution, the better and most preferably saturated. The acidic aqueous solution is an aqueous solution such as dilute hydrochloric acid, dilute nitric acid, dilute sulfuric acid, formic acid, acetic acid, propionic acid, butyric acid, or a buffer solution (acetate, etc.) having a pH of 7 or less, and has a pH in the range of 3 to 6.5. It is preferable that

Next, the alkaline compound is diluted directly with this solution, preferably with water, as a 5% by weight or less diluted alkaline aqueous solution, more preferably as a 1% by weight or less diluted alkaline aqueous solution, and even more preferably 1% by weight or less. Add by vapor diffusion of dilute alkaline aqueous solution.
Alkaline compounds include triethylamine, methylamine, ethylamine, propylamine, butylamine, diethylamine, N-ethylmethylamine, N-methylpropylamine, dipropylamine, trimethylamine, N, N-dimethylethylamine, N, N-dimethylisopropyl Amine, N, N-dimethylbutylamine, N, N-diethylmethylamine, tripropylamine, sodium hydroxide, lithium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, barium hydroxide, etc. it can. Furthermore, you may use the mixed solution which mixed 2 or more types of these alkaline compounds.
As a result, the ammonium cation formed at the end of the peptide lipid is deprotonated by an alkaline compound to become an amine, and a hollow fibrous substance is precipitated from the solution depending on the decrease in solubility in an aqueous solution.

(2) Next, the hollow fibrous material is recovered from the solution, dried under reduced pressure, and stable in the air. The average outer diameter is 20 to 700 nm, preferably 40 to 400 nm, and the average inner diameter (hollow A hollow fiber-like organic nanotube having an average diameter) of 10 to 500 nm, preferably 20 to 200 nm, and a length of several hundred nm to several hundred μm is obtained.
The conditions for heat drying under reduced pressure are to dry for 2 hours or more at a reduced pressure of 20 Pa or less in a temperature range from room temperature to 60 ° C. The higher the heating temperature is 60 ° C. or lower, the shorter the drying time is. However, in consideration of the effect on the thermal stability of peptide lipids, 40 ° C. or lower is preferable. More preferable drying conditions are 24 to 48 hours at 30 ° C.

  An optical microscope, a laser microscope, a scanning electron microscope, a transmission electron microscope, an atomic force microscope, etc. are used for confirmation of the form and size dimension of the hollow fiber-like organic nanotube. In an optical microscope or a laser microscope, it is generally difficult to detect a fibrous structure having an outer diameter of several hundred nm or less without using a technique such as a staining method. The scanning electron microscope is a very effective observation means for observing the surface and morphology of the fibrous structure. Depending on the orientation of the fiber structure, the hollow cylinder structure can be confirmed directly, but it is not universal. The transmission electron microscope can express the hollow cylinder structure with the contrast of light and shade, so the hollow cylinder structure can be confirmed, but the same contrast image can be obtained even when the widthwise ends of the ribbon-like structure are slightly rolled up. Therefore, when used alone, it is a little dangerous to conclude with a hollow cylinder structure. Therefore, it is desirable to use a scanning electron microscope and a transmission electron microscope in combination in order to confirm the presence of the hollow fiber form.

EXAMPLES Next, although an Example demonstrates this invention still in detail, this invention is not limited at all by these examples.
(Production Example 1)
[Synthesis of N-tetradecanoyl-glycylglycine]
To 0.57 g (2.2 mmol) of glycylglycine benzyl ester hydrochloride was added 0.31 ml (2.2 mmol) of triethylamine and dissolved in 10 ml of ethanol. 50 ml of chloroform solution containing 0.46 g (2 mmol) of tridecanecarboxylic acid was added thereto. While cooling this mixed solution at −10 ° C., 20 ml of a chloroform solution containing 0.42 g (2.2 mmol) of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride was added and gradually returned to room temperature. Stir all day and night. The reaction solution was washed with 50 ml of 10 wt% aqueous citric acid solution, 50 ml of 4 wt% aqueous sodium hydrogen carbonate solution and 50 ml of pure water, and then concentrated to dryness using a rotary evaporator (pressure 10 KPa, evaporation temperature 40 ° C.) to give a white solid (N -Tetradecanoyl-glycylglycine benzyl ester) 0.57 g (yield 65%) was obtained. 0.43 g (1 mmol) of the obtained compound was dissolved in 100 ml of dimethylformamide, and 0.5 g of 10 wt% palladium / carbon was added as a catalyst to perform catalytic hydrogen reduction. After 6 hours, filtration through Celite, followed by concentration and drying using a rotary evaporator (pressure 10 KPa, evaporation temperature 40 ° C.), R in the general formula (1) RCO (NH—CHR′—CO) _m OH is tridecyl. 0.21 g (yield 60%) of N-tetradecanoyl-glycylglycine, which is a group, m is 2, and R ′ is both H.
Melting point: 158 ° C
Elemental analysis (C ₁₈ H ₃₄ N ₂ O ₄ )
Calculated (%) C63.13, H10.01, N8.18
Actual value (%) C62.09, H9.65, N8.25

(Production Example 2)
[Synthesis of N-dodecanoyl-glycylglycine]
To 0.57 g (2.2 mmol) of glycylglycine benzyl ester hydrochloride was added 0.31 ml (2.2 mmol) of triethylamine and dissolved in 10 ml of ethanol. To this was added 50 ml of a chloroform solution containing 0.40 g (2 mmol) of undecanecarboxylic acid. While cooling this mixed solution at −10 ° C., 20 ml of a chloroform solution containing 0.42 g (2.2 mmol) of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride was added and gradually returned to room temperature. Stir all day and night. The reaction solution was washed with 50 ml of 10 wt% aqueous citric acid solution, 50 ml of 4 wt% aqueous sodium hydrogen carbonate solution and 50 ml of pure water, and then concentrated to dryness using a rotary evaporator (pressure 10 KPa, evaporation temperature 40 ° C.) to give a white solid (N -Dodecanoyl-glycylglycine benzyl ester) 0.50 g (yield 60%) was obtained. 0.42 g (1 mmol) of the obtained compound was dissolved in 100 ml of dimethylformamide, and 0.5 g of 10 wt% palladium / carbon was added as a catalyst to perform catalytic hydrogen reduction. After 6 hours, filtration through Celite, and then concentrating to dryness using a rotary evaporator (pressure 10 KPa, evaporation temperature 40 ° C.), R in the general formula (1) RCO (NH—CHR′—CO) _m OH is undecyl. 0.16 g (yield 50%) of N-dodecanoyl-glycylglycine, which is a group, m is 2 and R ′ is both H, is obtained.
Melting point: 160 ° C
Elemental analysis _{(C 16 H 30 N 2 O} 4 · 0.5H 2 O)
Calculated (%) C59.41, H9.66, N8.66
Actual value (%) C60.09, H9.34, N8.58

(Production Example 3)
[Synthesis of N-dodecanoyl-glycylglycylvaline]
To 0.93 g (2.2 mmol) of glycylglycylvaline benzyl ester hydrochloride was added 0.31 ml (2.2 mmol) of triethylamine and dissolved in 10 ml of ethanol. To this was added 50 ml of a chloroform solution containing 0.40 g (2 mmol) of undecanecarboxylic acid. While cooling this mixed solution at −10 ° C., 20 ml of a chloroform solution containing 0.42 g (2.2 mmol) of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride was added and gradually returned to room temperature. Stir all day and night. The reaction solution was washed with 50 ml of 10 wt% aqueous citric acid solution, 50 ml of 4 wt% aqueous sodium hydrogen carbonate solution and 50 ml of pure water, and then concentrated to dryness using a rotary evaporator (pressure 10 KPa, evaporation temperature 40 ° C.) to give a white solid (N 0.45 g (yield 45%) of -dodecanoyl-glycylglycylvaline benzyl ester) was obtained. 0.45 g (0.9 mmol) of the obtained compound was dissolved in 100 ml of dimethylformamide, and 0.5 g of 10 wt% palladium / carbon was added as a catalyst to perform catalytic hydrogen reduction. After 6 hours, filtration through Celite, and then concentrating to dryness using a rotary evaporator (pressure 10 KPa, evaporation temperature 40 ° C.), R in the general formula (1) RCO (NH—CHR′—CO) _m OH is undecyl. 0.22 g (yield 60%) of N-dodecanoyl-glycylglycylvaline, which is a group, m is 3, and R ′ is H, H, (CH ₃ ) ₂ CH— from the left, was obtained.
Melting point: 130 ° C
Elemental analysis (C ₂₁ H ₃₉ N ₃ O ₅ )
Calculated value (%) C60.99, H9.51, N10.16
Actual value (%) C61.11, H9.24, N9.68

(Production Example 4)
[Synthesis of N-tridecyl-glycylglycinamide hydrochloride]
To 0.51 g (2.2 mmol) of t-butyloxycarbonyl-glycylglycine, 0.31 ml (2.2 mmol) of triethylamine was added and dissolved in 10 ml of ethanol. To this was added 50 ml of a chloroform solution containing 0.40 g (2 mmol) of tridecylamine. While cooling this mixed solution at −10 ° C., 20 ml of a chloroform solution containing 0.42 g (2.2 mmol) of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride was added and gradually returned to room temperature. Stir all day and night. The reaction solution was washed with 50 ml of 10 wt% aqueous citric acid solution, 50 ml of 4 wt% aqueous sodium hydrogen carbonate solution and 50 ml of pure water, concentrated to dryness using a rotary evaporator (pressure 10 KPa, evaporation temperature 40 ° C.), and oil (N- Tridecyl-t-butyloxycarbonyl-glycylglycinamide) was obtained. The obtained oil was dissolved in 100 ml of chloroform, and 10 ml of 4N hydrochloric acid / ethyl acetate was added to deprotect the peptide. After 4 hours, by concentrating to dryness using a rotary evaporator (pressure 10 KPa, evaporation temperature 40 ° C.), in formula (2) H (NH—CHR′—CO) _m NHR, R is a tridecyl group, m N-tridecyl-glycylglycinamide hydrochloride 0.19 g (yield 27%), in which R ′ is 2 and both R ′ are H.
Melting point: 140 ° C
Elemental analysis (C ₁₇ H ₃₆ ClN ₃ O ₂・ 1.5H ₂ O)
Calculated (%) C54.6, H10.43, N11.15
Actual value (%) C53.81, H10.86, N11.43

(Production Example 5)
[Synthesis of N-tetradecyl-glycylglycinamide hydrochloride]
To 0.51 g (2.2 mmol) of t-butyloxycarbonyl-glycylglycine, 0.31 ml (2.2 mmol) of triethylamine was added and dissolved in 10 ml of ethanol. To this, 50 ml of a chloroform solution containing 0.43 g (2 mmol) of tetradecylamine was added. While cooling this mixed solution at −10 ° C., 20 ml of a chloroform solution containing 0.42 g (2.2 mmol) of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride was added and gradually returned to room temperature. Stir all day and night. The reaction solution was washed with 50 ml of 10 wt% aqueous citric acid solution, 50 ml of 4 wt% aqueous sodium hydrogen carbonate solution and 50 ml of pure water, concentrated to dryness using a rotary evaporator (pressure 10 KPa, evaporation temperature 40 ° C.), and oil (N- Tetradecyl-t-butyloxycarbonyl-glycylglycinamide) was obtained. The obtained oil was dissolved in 100 ml of chloroform, and 10 ml of 4N hydrochloric acid / ethyl acetate was added to deprotect the peptide. After 4 hours, by concentrating to dryness using a rotary evaporator (pressure 10 KPa, evaporation temperature 40 ° C.), in formula (2) H (NH—CHR′—CO) _m NHR, R is a tetradecyl group, m N-tetradecyl-glycylglycinamide hydrochloride 0.38 g (yield 52%) in which R ′ is 2 and both R ′ are H.
Melting point: 150 ° C
Elemental analysis (C ₁₈ H ₃₈ ClN ₃ O ₂ · H ₂ O)
Calculated (%) C56.60, H10.56, N11.00
Actual value (%) C56.10, H10.88, N11.44

Example 1
[Synthesis of N-dodecanoyl-glycylglycine hollow fiber organic nanotube]
When 0.031 g of N-dodecanoyl-glycylglycine obtained in Production Example 2 is dissolved in 100 ml of 10 mM aqueous sodium hydroxide solution and then the solution is neutralized by vapor diffusion of 1% dilute acetic acid aqueous solution, a white precipitate is deposited. . The obtained white powder was further dried under reduced pressure (10 Pa) at 50 ° C. for 12 hours to obtain N-dodecanoyl-glycylglycine hollow fiber organic nanotubes (yield: 0.025 g). Observation with a transmission electron microscope and a scanning electron microscope revealed that hollow fiber-like organic nanotubes having an average outer diameter of 75 nm were formed. A scanning electron micrograph is shown in FIG.

(Example 2)
[Synthesis of N-tetradecanoyl-glycylglycine hollow fiber organic nanotube]
When 0.033 g of N-tetradecanoyl-glycylglycine obtained in Production Example 1 is dissolved in 100 ml of 1 mM sodium hydroxide aqueous solution and then neutralized by vapor diffusion of 1% dilute acetic acid aqueous solution, white precipitate is formed. Precipitate. The obtained white powder was further dried under reduced pressure (10 Pa) at 40 ° C. for 24 hours to obtain N-tetradecanoyl-glycylglycine hollow fiber organic nanotubes (yield: 0.028 g). Observation with a transmission electron microscope and a scanning electron microscope revealed that hollow fiber-like organic nanotubes having an average outer diameter of 70 nm were formed. A scanning electron micrograph is shown in FIG.

(Example 3)
[Synthesis of N-dodecanoyl-glycylglycine hollow fiber organic nanotube]
When 3 g of N-dodecanoyl-glycylglycine obtained in Production Example 2 is dissolved in 50 ml of 100 mM sodium hydroxide aqueous solution and then the solution is neutralized by adding 50 ml of 100 mM hydrochloric acid, a white precipitate is deposited. The resulting white powder was further dried under reduced pressure (10 Pa) at room temperature for 48 hours to obtain N-dodecanoyl-glycylglycine hollow fiber organic nanotubes (yield: 2.2 g). Observation with a transmission electron microscope and an atomic force microscope revealed that hollow fiber-like organic nanotubes having an average outer diameter of 90 nm were formed. An atomic force micrograph is shown in FIG.

Example 4
[Synthesis of N-dodecanoyl-glycylglycylvaline hollow fiber organic nanotube]
When 0.041 g of N-dodecanoyl-glycylglycylvaline obtained in Production Example 3 is dissolved in 100 ml of 10 mM sodium hydroxide aqueous solution and then the solution is neutralized by vapor diffusion of 1% dilute acetic acid aqueous solution, a white precipitate is precipitated. To do. The obtained white powder was further dried under reduced pressure (10 Pa) at room temperature for 48 hours to obtain N-dodecanoyl-glycylglycylvaline hollow fiber organic nanotubes (yield: 0.035 g). Observation with a transmission electron microscope and a scanning electron microscope revealed that hollow fiber-like organic nanotubes having an average outer diameter of 45 nm were formed. A transmission electron micrograph is shown in FIG.

(Example 5)
[Synthesis of N-tridecyl-glycylglycinamide hollow fiber organic nanotube]
When 0.034 g of N-tridecyl-glycylglycinamide hydrochloride obtained in Production Example 4 is dissolved in 100 ml of water and then the solution is neutralized by vapor diffusion of a 1% triethylamine aqueous solution, a white precipitate is deposited. The obtained white powder was further dried under reduced pressure (10 Pa) at 40 ° C. for 12 hours to obtain N-tridecyl-glycylglycinamide hollow fiber organic nanotubes (yield: 0.025 g). Observation with a transmission electron microscope and a scanning electron microscope revealed that hollow fiber-like organic nanotubes having an average outer diameter of 180 nm were formed. A scanning electron micrograph is shown in FIG.

(Example 6)
[Synthesis of N-tetradecyl-glycylglycinamide hollow fiber organic nanotube]
When 0.036 g of N-tetradecyl-glycylglycinamide hydrochloride obtained in Production Example 5 is dissolved in 100 ml of water and then the solution is neutralized by vapor diffusion of a 1% triethylamine aqueous solution, a white precipitate is deposited. The obtained white powder was further dried under reduced pressure (10 Pa) at 40 ° C. for 12 hours to obtain N- (glycylglycine) tetradecylamide hollow fibrous organic nanotubes (yield: 0.030 g). Observation with a transmission electron microscope and a scanning electron microscope revealed that hollow fiber-like organic nanotubes having an average outer diameter of 110 nm were formed. A scanning electron micrograph is shown in FIG.

  The hollow fiber-like organic nanotube of the present invention is used, for example, as a material for inclusion / separation of drugs and useful biomolecules, drug delivery materials in the fine chemical industry, medicine, cosmetics field, etc., or coated with a conductive substance or metal on the nanotube. By doing so, it can be used in the field of electronics and information as a microelectronic component. In addition, it is useful as an artificial blood vessel, nanotube capillary, and nanoreactor using a micro tube structure in the fields of medicine, analysis, and chemical production, and has high industrial utility value, so it can contribute to these various fields. I can do it.

2 is a scanning electron micrograph of Example 1. FIG. 2 is a scanning electron micrograph of Example 2. 4 is an atomic force micrograph of Example 3. 4 is a transmission electron micrograph of Example 4. 6 is a scanning electron micrograph of Example 5. 6 is a scanning electron micrograph of Example 6.

Claims (14)

The following general formula (1)
RCO (NH—CHR′—CO) _m OH (1)
(Wherein R represents a hydrocarbon group having 6 to 24 carbon atoms, R ′ represents an amino acid side chain, and m represents 2 or 3 ), a step of dissolving the peptide lipid in an alkaline aqueous solution, acidic to the solution A method for producing hollow fiber-like organic nanotubes, comprising the steps of adding a compound, and recovering the hollow fiber-like organic nanotubes produced by self-assembly in a solution from the solution, followed by air drying or drying under reduced pressure at room temperature.   The method for producing a hollow fiber-like organic nanotube according to claim 1, wherein m in the general formula (1) is 2.   The method for producing a hollow fiber-like organic nanotube according to claim 2, wherein the peptide is glycylglycine.   The alkaline aqueous solution is a weak alkaline aqueous solution containing an alkali metal hydroxide or an alkaline earth metal hydroxide or a buffer solution having a pH of 7 or more, and the pH is adjusted in the range of 7.5 to 12. The manufacturing method of the hollow fiber-like organic nanotube as described in any one of -3.   The said acidic compound is an organic acid, The manufacturing method of the hollow fiber-like organic nanotube as described in any one of Claims 1-3.   The method for producing hollow fiber organic nanotubes according to any one of claims 1 to 3, wherein the alkaline aqueous solution is an aqueous sodium hydroxide solution adjusted to pH 7.5, and the acidic compound is derived from acetic acid. The following general formula (2)
H (NH—CHR′—CO) _m NHR (2)
(Wherein R represents a hydrocarbon group having 6 to 24 carbon atoms, R ′ represents an amino acid side chain, m represents 2 or 3 ), a step of dissolving the peptide lipid in an acidic aqueous solution, and the solution is alkaline. A method for producing hollow fiber-like organic nanotubes, comprising the steps of adding a compound, and recovering the hollow fiber-like organic nanotubes produced by self-assembly in a solution from the solution, followed by air drying or drying under reduced pressure at room temperature.   The method for producing hollow fiber-like organic nanotubes according to claim 7, wherein m in the general formula (2) is 2.   The method for producing hollow fiber-like organic nanotubes according to claim 8, wherein the peptide is glycylglycine.   The hollow according to any one of claims 7 to 9, wherein the acidic aqueous solution is a weakly acidic aqueous solution containing an acidic compound or a buffer solution having a pH of 7 or less, and the pH is adjusted in the range of 3 to 6.5. A method for producing fibrous organic nanotubes.   The method for producing hollow fiber-like organic nanotubes according to any one of claims 7 to 9, wherein the alkaline compound is an alkylamine.   The method for producing hollow fiber-like organic nanotubes according to any one of claims 7 to 9, wherein the acidic aqueous solution is dilute hydrochloric acid, and the alkaline compound is triethylamine.   The hollow fiber-like organic nanotube manufactured by the method as described in any one of Claims 1-12.   The hollow fiber-like organic nanotube according to claim 13, wherein the average outer diameter is 20 to 700 nm and the average inner diameter is 10 to 500 nm.