US20060140847A1

US20060140847A1 - Method for introducing functional material into organic nanotube

Info

Publication number: US20060140847A1
Application number: US10/544,800
Authority: US
Inventors: Bo Yang; Toshimi Shimizu; Shoko Kamiya
Original assignee: Individual
Current assignee: Japan Science and Technology Agency; National Institute of Advanced Industrial Science and Technology AIST
Priority date: 2003-02-18
Filing date: 2004-02-12
Publication date: 2006-06-29
Also published as: WO2004074171A1; JP2004261885A

Abstract

The objective is to easily introduce a desired functional substance into organic nanotubes under milder conditions such as ambient temperature and ambient pressure. The method comprises the steps of allowing a surface active organic compound comprising hydrophobic hydrocarbon groups and hydrophilic groups to self aggregate in liquid phase to form organic nanotubes having an internal cavity size of at least 5 nm (step 1), freeze drying the organic nanotubes (step 2), dissolving or dispersing a desired functional substance in a solvent (step 3) and dispersing said freeze dried organic nanotubes in the solvent or the dispersion at or below the gel-liquid crystal phase transition temperature of said surface active organic compound (step 4). The organic nanotubes formed can be used in a variety of applications depending on the properties of the functional substance.

Description

TECHNICAL FIELD

The present invention relates to a method for introducing a desired functional substance into the hollow cylinder shaped cavity of organic nanotubes, in a solvent, having an internal cavity diameter of 5 nm or more.

PRIOR ART

Ever since carbon nanotubes were discovered by Dr. Iijima, basic and application research to utilize nanotube shapes of the hollow cylinder with nanometer sized cavities have been pursued vigorously. Of the studies, research to prepare nano wires and nano devices by packing the hollow cylinder shaped cavities in nanotubes with a metal or a metal oxide has been attracting attention recently.
The methods used to introduce a metal or a metal oxide to the interior of carbon nanotubes can be roughly divided into dry and wet methods. Among the dry methods, an arc discharge method [C. Guerret-Piecourt et al. Nature, 372, 761 (1994)] and a chemical vacuum deposition method (CVD method) [B. K. Pradhan, et al., Chemical Material, 10, 2510 (1998)] are typically used. Both methods require high temperatures and high vacuum. An example of a wet method in which carbon nanotubes were treated using a nickel nitrate and a fused nickel nitrate was introduced into carbon nanotubes at a high temperature (140° C. or higher) has been reported [S. C. Tsang, et al., Nature, 372, 159 (1994)].
On the other hand, large amounts of organic nanotubes are easily formed in water (or in a solvent) when organic molecules are allowed to self-assemble, and many biologically derived nanotubes have also been formed. Therefore, nanotubes are expected to yield novel materials. (Unexamined Japanese Patent Applications Nos. 2002-80489, 2002-322190 and Japanese Patent Applications Nos. 2002-35035, 2002-49238, 2002-49239, 2002-61797 and 2003-13266.)
However, a suitable method to provide these organic nanotubes with functional substances was unavailable in spite of the fact that many avenues of applications are expected to open up as various substances are introduced into these organic nanotubes.
That is, these organic nanotubes are synthesized in water (solvent), and the tube interiors are filled with the solvent. Therefore, a substance might be introduced into a tube interior through a target substance diffusion in a solution. In addition, a carbon nanotube introduction method involved first the opening of the cap closing a carbon nanotube tip using a strong acid such as a mixed acid at a high temperature (140° C. or higher), followed by the introduction of a target substance at a high temperature and under high vacuum. Therefore, this method cannot be applied to flexible organic nanotubes. Thus a method to introduce a functional substance into inside the tubes under mild conditions suited for organic nanotubes was needed.
Problems for the Invention to Solve
The present invention offers a method to easily introduce a desired functional substance into an organic nanotube under mild conditions such as ambient temperature and ambient pressure.
Means to Solve the Problems
The inventors conducted intensive studies to solve the problem described above. As a result, the fact was discovered that a desired substance can be introduced into the inside of an organic nanotube by dispersing the nanotube in a solution or a dispersion of a desired functional substance after the water (or a solvent) inside the nanotubes is once removed by freeze drying. The present invention was completed based on this discovery.
That is, the present invention is a method for introducing a functional substance into organic nanotubes comprising the steps of allowing a surface active organic compound comprising hydrophobic hydrocarbon groups and hydrophilic groups to self aggregate in liquid phase to form organic nanotubes having an internal cavity size of at least 5 nm (step 1), freeze drying the organic nanotubes (step 2), dissolving or dispersing a desired functional substance in a solvent (step 3) and dispersing said freeze dried organic nanotubes in the solvent or the dispersion at or below the gel-liquid crystal phase transition temperature of said surface active organic compound (step 4).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a TEM photograph of the tubes obtained in Example 1. (a) shows the configuration before freeze drying, and (b) shows the configuration after freeze drying.
FIG. 2 shows a TEM photograph of the organic nanotubes of Example 1 packed with gold nanocrystals. (a) shows a low magnification TEM photograph, (b) shows a high magnification TEM photograph and (c) shows the electron diffraction pattern.
FIG. 3 shows a TEM photograph of the organic nanotubes of Example 2 packed with colloidal gold. The material adhering to the top right side of the tubes is a colloidal gold coagulant.

DETAILED DESCRIPTION OF THE INVENTION

The method of the present invention will be explained below step by step.
(1) Step 1.
In this step, a surface activated organic compound self aggregates to form hollow nanotubes when the surface activated organic compound is dissolved in a solvent composed mainly of water. The surface activated organic compound comprises hydrophobic hydrocarbon groups and hydrophilic groups. The hydrocarbon groups are preferably hydrocarbon chains containing from about 6 to 50 carbon atoms. A linear hydrocarbon is preferred, and it may be saturated or unsaturated. When the hydrocarbon is unsaturated, the presence of three or fewer double bonds is preferred. The hydrophilic groups are preferably at least one selected from the group comprising saccharide chains, peptide chains and metal salts. These hydrophilic groups and hydrophobic groups are bonded directly or through an amide linkage, arylene group or arylene oxy group.
The compounds developed by the inventors' laboratory and described below can be cited as the surface activated organic compound:

(a) An O-glycoside type glycolipid having a structure shown by the general formula below. (Unexamined Japanese Patent Application No. 2002-80489 and Japanese Patent Application No. 2002-61797)

(In the formula, G represents a saccharide group and R represents a hydrocarbon group containing 6 to 25 carbon atoms.)
(b) An asymmetric double head type lipid represented by the general formula R′—NHCO—(CH₂)_n—COOH. (In the formula, R′ represents an aldopyranose radical from which the terminal reducing hydroxyl group is excluded, and n represents 6 to 20.) (Unexamined Japanese Patent Application No. 2002-322190)
(c) An N-glycoside type glycolipid represented by the general formula below. (Japanese Patent Application No. 2003-13266)
G′-NHCO—R″
(In the formula G′ represents a saccharide radical from which a hemiacetal hydroxyl group bonded to the anomer carbon atom in the saccharide is excluded, and R″ represents an unsaturated hydrocarbon group containing 10 to 39 carbon atoms.)
(d) A compound comprising a transition metal and a peptide lipid represented by the general formula
R′″CO(NHCH₂CO)_mOH. (In the formula R′″ represents a hydrocarbon group containing 6 to 18 carbon atoms, and m represents an integer of 1 to 3.) (Japanese Patent Application No. 2003-039276.)

When dissolved in a solvent, these types of compounds self aggregate to form hollow nanotubes. The following conditions can be cited as preferred conditions.
An aqueous solution of the above mentioned surface active organic compound is heated to a designated temperature (40° C.-100° C.), and this aqueous solution is allowed to cool to a designated temperature (from the freezing point of the aqueous solution to 30° C.) at a designated cooling rate (5.0° C./min or less). Then this aqueous solution is maintained at this maintenance temperature for a designated time span (at least a day).
The above mentioned surface active organic compounds self aggregate and form hollow nanotubes using this type of process. The size varies with the conditions, but ordinarily the inner cavity diameter is at least 5 nm, preferably 500 nm or less, and from 10 nm to 200 nm is particularly preferred. Also, the external diameter is 1,000 nm or less, and from 50 nm to 300 nm is particularly preferred. Even when nanotubes having an inner cavity diameter of less than 5 nm are present, the nanotubes may be used for the method of the present invention if nanotubes having an inner cavity diameter of at least 5 nm are the major component.
As the solvent used here, water such as distilled water, purified water, super pure water and the like, various salt solutions, pH buffer solutions comprising phosphoric acid and the like may be used. The concentration of the surface active organic compound is preferably from 0.001% by w/v to 0.02% by w/v.
(2) Step 2
In this step, the hollow nanotubes formed in the step 1 qre freeze dried.
The freezing temperature in the freeze drying process is preferably −70° C. or lower; freezing in liquid nitrogen is simple. The degree of vacuum in the freeze drying process is preferably 20 PA or lower, and 1.0 PA or lower is more preferred. The duration of the freeze drying time is preferably at least 24 hours, and at least 72 hours is more preferred.
(3) Step 3.
In this step a desired functional substance is dissolved or dispersed in a solvent. This solvent is different from the solvent used in the step 1 and is water or an organic solvent. The type of the solvent and the concentration of the functional substance may be appropriately selected according to the functional substance and the objective.
The functional substance is not particularly restricted and may be appropriately selected according to the objective. This functional substance is used in the form of a solution if it dissolves in a solvent but may be used in the form of a dispersion if fine particles (about 50 nm is a desirable size based on the atom size) can be dispersed even if they cannot be dissolved. The examples of the functional substances and the methods with which they are used are cited below.
(a) Metals.
In this case, a metal may be used as an aqueous solution of the metal salt. Chlorides, nitrates, sulfates, acetates, hydroxides and the like may be cited as the metal salt,.
(b) Metals, Metal Oxides, Metal Sulfides, Dentrimers, Carbon Nanotubes and Polymers.
In this case, a colloidal dispersion of these functional substances may be used.
(c) Physiologically Active Materials.
These materials may be used as solutions without any further treatments. Immunity proteins, nucleic acids, low molecular weight organic compounds, non-immunity proteins, immunoglobulin bondable proteins, saccharide bondable proteins, enzymes, microorganism and the like may be cited as the physiologically active materials,.
(d) Pharmaceutical Drug Materials.
These materials may be used as solutions or dispersions. Pharmaceutical drug for medical treatments, diagnostic drugs, imaging agents and medical substances as active ingredients in cosmetic products may be cited.
(4) Step 4.
In this step, the organic nanotubes dried in step 2 are dispersed in the functional substance solution or dispersion prepared in step 3. This functional substance solution or dispersion is thought to be suctioned into the tube interior by the suction power of a capillary phenomenon. The amount of the organic nanotubes added is not particularly restricted and may be appropriately selected according to the end use objectives, the functional substance concentration in the solutions, the size of the organic nanotubes and the like.
In this step, the solvent temperature is at or below the gel-liquid crystal phase transition temperature of the surface active organic compound, preferably ambient temperature, that is, a temperature that does not involve heating or cooling particularly is preferred.
This gel-liquid crystal phase transition temperature can be measured using a differential scanning calorimetric method. More specifically, 1 to 5 milligrams of a surface active organic compound is mixed with 30-50 microliters of water to completely hydrate the compound. This sample is analyzed using a calorimeter, and the gel-liquid crystal transition is observed as an endothermic peak. The temperature for the maximum peak position is referred to as the phase transition temperature.
This gel-liquid crystal phase transition temperature corresponds in colloid chemistry to the melting point of a surfactant in water. When an aqueous dispersion is heated to this temperature or above, the tubular structure changes its conformation to vesicle (endoplasmic reticulum) immediately and the tubular structure is destroyed. This gel-liquid crystal phase transition temperature depends on the type of surface active organic compound but is ordinarily from about 30° C. to 90° C. It is preferably conducted at atmospheric pressure, but the pressure of less than 0.2 MPa may be added.
Effect of the Invention
When various functional substances are introduced into organic nanotubes, various applications are made possible depending on the functional substance properties. For example, DDS and cosmetic products applications are made possible when active ingredients such as pharmaceutical drugs, proteins, DNA and the like are encapsulated, and sensor device applications become possible when metals are introduced.
The present invention is illustrated using examples below, but the examples are not intended to restrict the present invention.

PRODUCTION EXAMPLE 1

D-(+)-Glucopyranose (1.0 g, 5.55 millimoles manufactured by the Fluka Co.) was placed in a flask, and 50 ml of water was added to dissolve it. Ten grams of ammonium hydrogen carbonate (Wako Pure Chemical Industries, Ltd.) was added to the solution until crystals separated out in the bottom of the flask. The mixture was agitated using a magnetic stirrer for three to five days in an oil bath at 37° C. Ammonium hydrogen carbonate was added from time to time to maintain saturation in the reaction system. The total amount of ammonium hydrogen carbonate added was from 40 g to 50 g. The reaction was monitored using thin layer chromatography [Rf value=0.40, developing solvent: ethyl acetate/acetic acid/methanol/water (volume ratio 4/3/3/1)].
The reaction system was cooled to allow ammonium hydrogen carbonate crystals to separate out in a post treatment to remove unreacted ammonium hydrogen carbonate from the reaction system. A different method may be used. For example, a suitable amount of water may be added to the reaction system and vaporized by concentrating it or a desalination device may be utilized to remove unreacted ammonium hydrogen carbonate. β-D-Glucopyranosylamine was obtained in this manner.

PRODUCTION EXAMPLE 2

A reaction system was created by placing 11-cis-Octadecenoic acid (282 mg, 1.0 millimole) (Wako Pure Chemical Industries, Ltd.) dissolved in 1 ml of dimethyl sulfoxide. HOBt (153 mg, 1.0 millimole) (Wako Pure Chemical Industries, Ltd.) and BOP (1.33 g, 3.0 millimoles) (Wako Pure Chemical Industries, Ltd.) dissolved in 1.5 ml of dimethyl sulfoxide were added to the reaction system, and the system was agitated using a magnetic stirrer for ten minutes at 25° C.
Next, the β-D-glucopyranosylamine (1.24 g, 6.9 millimoles) obtained in Production Example 1 was added to the reaction system, and the system was agitated using a magnetic stirrer for at least five hours at 25° C. to allow a reaction to occur. The reaction was monitored using thin layer chromatography [Rf value=0.56, developing solvent: chloroform/methanol (volume ratio 4/1)].
The crude product obtained was chromatographed using silica gel chromatography with a mixed solvent of chloroform/methanol (volume ratio 4/1) as the elution solution. Next, column chromatography was conducted using gel permeation agent Toyopearl HW-40S (Tosoh Corp.) with methanol as the elution solution to obtain white solids of N-(11-cis-octadecenoyl)-β-D-glucopyranosylamine (85 mg, 19% yield).
The physical properties of this product are presented below.
Melting point: 148° C.

Elemental analysis (C₂₄H₄₅O₆N)

C H N

Calculated (%) 64.98 10.22 3.16

Experimental (%) 63.68 10.02 3.16

PRODUCTION EXAMPLE 3

5 milligrams of the N-(11-cis-octadecenoyl)-β-D-glucopyranosylamine obtained in Production Example 2 was dispersed unltrasonically in 100 ml of pure water for 40 minutes. The dispersion was subsequently boiled for an hour at 110° C., allowed to cool to ambient temperature and left standing overnight.
The aqueous solution obtained was examined using a transmission type electron microscope (TEM), and hollow fiber shaped organic nanotubes having an internal diameter of 45-200 nm and an external diameter of 75-500 nm were confirmed. [See FIG. 1(a).]

EXAMPLE 1

A dispersion of the organic nanotubes obtained in Production Example 3 was placed for ten minutes in liquid nitrogen (−196° C.) and was completely frozen. The frozen dispersion was subsequently transferred to a freeze drying machine (Tokyo Rikakikai Co., Ltd.) and was dried for 72 hours in vacuum (<1 Pa) at 25° C. The tubes were subsequently removed, and their structure was confirmed using TEM. The results are shown in FIG. 1(b). The tubular structure was not destroyed and was maintained unchanged before and after freeze drying.
Next, the dried organo nanotube powder and 10 ml of a gold chloride solution (5 mM HAuCl₄; 50 mM tris hydrochloride) were mixed by agitation. The bulk of the gold chloride solution was removed after an hour using an ultra centrifuging method and washed was conducted five times using pure water. The gold chloride containing nanotubes were subsequently irradiated for 40 minutes using UV light [a low pressure mercury lamp (UVB-10), 135W, λ=254 nm manufactured by Sen Tokushu Kogen Co., Ltd.). This operation reduced gold chloride into gold.
This organic nanotubes were examined using TEM. The results are shown in FIGS. 2(a) and (b). From FIGS. 2(a) and (b), the nano gold crystals were found to have packed the organic nanotubes. Furthermore, the electron beam diffraction of the fine gold nano particles of the organic nanotubes was measured using an electron beam diffraction device (Leo Corp.), and a diffraction pattern attributable to [111], [200], [220] and [311] faces was observed indicating that gold nano crystals gave rise to this diffraction pattern. That is, the gold chloride solution was thought to be introduced to the tube interior by the capillary suction force.

EXAMPLE 2

A gold colloid was prepared first. 98 milliliters of a gold chloride solution (0.01%) was placed in a 200 ml flask and was heated to boiling temperature (100° C.). 2 milliliters of a 1% by weight aqueous solution was added under agitation. The heating continued, and a reaction was allowed to proceed for 15 minutes. The reaction system was allowed to stand until it cooled to ambient temperature. The gold colloid solution obtained was a red wine color. The average particle size of the gold particles was 20 nm.
Next, the organic nanotube powder obtained in Production Example 3 by freeze drying was dispersed in 10 ml of the gold colloid solution, and the dispersion was agitated for an hour at ambient temperature and pressure.
This organic nanotubes were examined using TEM. The results are shown in FIG. 3. From the data presented in FIG. 3, the organic nanotubes were shown to be packed with colloidal gold particles.

Claims

1-5. (canceled)

6. An organic nanotube having an internal cavity size of at least 5 nm formed by self aggregating a surface active organic compound in liquid phase, wherein a functional substance is introduced into the internal cavity of the organic nanotubes, said surface active organic compound contains a hydrophobic hydrocarbon chain and at least one type of hydrophilic group selected from the group comprising saccharide chains, peptide chains and metal salts, and the hydrocarbon chain and the hydrophilic group are bonded directly or through an amide linkage, arylene group or arylene-oxy group.

7. The organic nanotube as in claim 6, wherein the functional substance is introduced into the internal cavity of the organic nanotubes by a method comprising the steps of freeze drying the organic nanotubes, dissolving or dispersing the desired functional substance in a solvent and dispersing said freeze dried organic nanotubes in the solvent or the dispersion at or below the gel-liquid crystal phase transition temperature of said surface active organic compound.

8. The organic nanotube as in claim 6 wherein said hydrophobic hydrocarbon chain is a hydrocarbon chain containing about 6 to 50 carbon atoms.

9. The organic nanotube as in claim 7 wherein said hydrophobic hydrocarbon chain is a hydrocarbon chain containing about 6 to 50 carbon atoms.

10. The organic nanotube as in claim 6 wherein said surface active organic compound is any one of (a) to (d) shown below:

(a) An O-glycoside type glycolipid having a structure shown by the general formula

whereinG represents a saccharide group and R represents a hydrocarbon group containing 6 to 25 carbon atoms;

(b) An asymmetric double head type lipid represented by the general formula R′—NHCO—(CH₂)n-COOH, wherein R′ represents an aldopyranose radical from which the terminal reducing hydroxyl group is excluded, and n represents 6 to 20;

(c) An N-glycoside type glycolipid represented by the general formula G′-NHCO—R″ wherein G′ represents a saccharide radical from which a hemiacetal hydroxyl group bonded to the anomer carbon atom in the saccharide is excluded, and R″ represents an unsaturated hydrocarbon group containing 10 to 39 carbon atoms;

(d) A compound comprising a transition metal and a peptide lipid represented by the general formula R′″CO(NHCH₂CO)_mOH, wherein R′″ represents a hydrocarbon group containing 6 to 18 carbon atoms, and m represents an integer of 1 to 3.

11. The organic nanotube as in claim 7 wherein said surface active organic compound is any one of (a) to (d) shown below:

12. The organic nanotube as in claim 8 wherein said surface active organic compound is any one of (a) to (d) shown below:

13. The organic nanotube as in any claim 6 wherein the solvent used for self aggregating the surface active organic compound in liquid phase is water, a saline solution or a pH buffer solution and the solvent used for introducing the functional substance into the internal cavity of the organic nanotubes is water or an organic solvent.

14. The organic nanotube as in claim 6 wherein the step of dissolving or dispersing the desired functional substance is conducted under atmospheric pressure and at ambient temperature.

15. The organic nanotube as in claim 6 wherein the freeze drying is conducted at −70° C. or lower, 20 Pa or lower and for at least 24 hours.

16. A method for introducing a functional substance into organic nanotubes in a solvent or in a dispersion comprising the steps of freeze drying an organic nanotubes having an internal cavity size of at least 5 nm formed by allowing a surface active organic compound to self aggregate in liquid phase, and dispersing said freeze dried organic nanotubes in the solvent or the dispersion at or below the gel-liquid crystal phase transition temperature of said surface active organic compound, wherein said surface active organic compound contains a hydrophobic hydrocarbon chain and at least one type of hydrophilic group selected from the group comprising saccharide chains, peptide chains and metal salts, and the hydrocarbon chain and the hydrophilic group are bonded directly or through an amide linkage, arylene group or arylene-oxy group.

17. The method as in claim 16 wherein said hydrophobic hydrocarbon chain is a hydrocarbon chain containing about 6 to 50 carbon atoms.

18. The method as in claim 16 wherein said surface active organic compound is any one of (a) to (d) shown below:

wherein G represents a saccharide group and R represents a hydrocarbon group containing 6 to 25 carbon atoms;

(c) An N-glycoside type glycolipid represented by the general formula G′-NHCO—R″, wherein G′ represents a saccharide radical from which a hemiacetal hydroxyl group bonded to the anomer carbon atom in the saccharide is excluded, and R″ represents an unsaturated hydrocarbon group containing 10 to 39 carbon atoms;

19. The method as in claim 17 wherein said surface active organic compound is any one of (a) to (d) shown below:

20. The method as in claim 16 wherein the solvent used for self aggregating the surface active organic compound in liquid phase is water, a saline solution or a pH buffer solution and the solvent used for introducing the functional substance into the internal cavity of the organic nanotubes is water or an organic solvent.

21. The method as in claim 17 wherein the solvent used for self aggregating the surface active organic compound in liquid phase is water, a saline solution or a pH buffer solution and the solvent used for introducing the functional substance into the internal cavity of the organic nanotubes is water or an organic solvent.

22. The method as in claim 18 wherein the solvent used for self aggregating the surface active organic compound in liquid phase is water, a saline solution or a pH buffer solution and the solvent used for introducing the functional substance into the internal cavity of the organic nanotubes is water or an organic solvent.