JP2014136793A - Method for producing aqueous dispersion of micelles of nitrogen-containing dendrimer compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing an aqueous dispersion of micelles of a nitrogen-containing dendrimer compound, the aqueous dispersion enabling the nitrogen-containing dendrimer compound to be soluble into water with high efficiency.SOLUTION: By mixing an organic solvent solution of a nitrogen-containing dendrimer compound that is obtained by dissolving the nitrogen-containing dendrimer compound into a solvent of low miscibility with water, and an aqueous buffer containing a surfactant at a predetermined concentration, followed by removing the organic solvent from the mixture obtained, an aqueous dispersion of micelles of the nitrogen-containing dendrimer compound, in which the nitrogen-containing dendrimer compound is solubilized with respect to water with high efficiency, is produced.

Description

  The present invention relates to a method for producing an aqueous dispersion of micelles of a nitrogen-containing dendrimer compound.

  Dendrimer compounds are large compounds having a dendritic structure, and it is known that compounds having various characteristics can be obtained according to the design. Among dendrimer compounds, nitrogen-containing dendrimer compounds containing a nitrogen-containing group such as an azomethine group can coordinate the metal to the nitrogen atom and incorporate the metal or metal compound into the molecule, so the catalyst Applications to materials, electronic materials, luminescent materials, etc. are expected.

  As described above, the nitrogen-containing dendrimer compound is expected to be applied to various uses. However, since the nitrogen-containing dendrimer compound is a hydrophobic compound, its range of use is limited to non-aqueous uses. For this reason, the method of solubilizing a nitrogen-containing dendrimer compound with respect to water is examined.

  As a method for solubilizing a nitrogen-containing dendrimer compound in water, for example, a nitrogen-containing dendrimer compound having a porphyrin skeleton is dissolved in a hydrophobic organic solvent such as chloroform together with a surfactant, and then a nitrogen-containing dendrimer compound There is known a method of mixing an organic solvent solution and an aqueous buffer solution, and then removing the organic solvent from the mixed solution of the organic solvent solution and the aqueous buffer solution (Patent Document 1).

JP 2008-222628 A

  In general, a nitrogen-containing dendrimer compound is an expensive compound obtained through a complicated synthesis process. For this reason, in order to use a nitrogen-containing dendrimer compound as efficiently as possible, solubilization of the nitrogen-containing dendrimer compound in water is required to be highly efficient. However, in the method described in the Examples of Patent Document 1, the solubilization rate of the nitrogen-containing dendrimer compound in water is only 60% at most, and a large amount of the nitrogen-containing dendrimer compound is not used.

  The present invention has been made in view of the above problems, and provides a method for producing an aqueous dispersion of micelles of a nitrogen-containing dendrimer compound, which can solubilize the nitrogen-containing dendrimer compound with high efficiency in water. The purpose is to provide.

  The inventors mixed an organic solvent solution of a nitrogen-containing dendrimer compound obtained by dissolving a nitrogen-containing dendrimer compound in a solvent having low miscibility with water, and an aqueous buffer containing a surfactant at a predetermined concentration. After that, by removing the organic solvent from the resulting mixture, it was found that a nitrogen-containing dendrimer compound micelle aqueous dispersion in which the nitrogen-containing dendrimer compound was solubilized with high efficiency in water could be produced. The invention has been completed.

In an embodiment of the present invention, an organic solvent solution of a nitrogen-containing dendrimer compound is prepared by dissolving a nitrogen-containing dendrimer compound having at least one nitrogen atom to which a metal element can coordinate in a solvent having low miscibility with water. A dendrimer solution preparation step;
A mixing step of mixing the organic solvent solution and an aqueous buffer containing a surfactant having a concentration of 5.0 × 10 ^{−4 to} 2.0 × 10 ⁻² mol / L;
It is a manufacturing method of the aqueous dispersion of the micelle of a nitrogen-containing dendrimer compound including the organic-solvent removal process which removes an organic solvent from the liquid mixture of the said organic-solvent solution and the said aqueous buffer.

  ADVANTAGE OF THE INVENTION According to this invention, the manufacturing method of the aqueous dispersion of the micelle of a nitrogen-containing dendrimer compound which can solubilize a nitrogen-containing dendrimer compound with respect to water can be provided.

≪Method for producing aqueous dispersion of micelle of nitrogen-containing dendrimer compound≫
The method for producing an aqueous dispersion of micelles of a nitrogen-containing dendrimer compound according to the present invention includes a dendrimer solution preparation step, a mixing step, and an organic solvent removal step. Hereinafter, the dendrimer solution preparation step, the mixing step, and the organic solvent removal step will be described in order.

<Dendrimer solution preparation process>
In the dendrimer solution preparation step, an organic solvent solution of a nitrogen-containing dendrimer compound is prepared by dissolving a nitrogen-containing dendrimer compound having at least one nitrogen atom to which a metal element can coordinate in a solvent having low miscibility with water. To do. Hereinafter, a method for preparing a nitrogen-containing dendrimer compound, an organic solvent, and an organic solvent solution of the nitrogen-containing dendrimer compound will be described in order.

[Nitrogen-containing dendrimer compound]
The nitrogen-containing dendrimer compound is not particularly limited as long as it has at least one nitrogen atom to which a metal element can coordinate. Examples of the nitrogen atom to which the metal element can coordinate include a nitrogen atom in an azomethine bond (—CH═N—). Preferable examples of the nitrogen-containing dendrimer compound containing an azomethine bond include a phenylazomethine dendrimer compound represented by the following general formula (1).

の構造で表され、Ｒ^１は、置換基を有してもよい芳香族基を表し、ｐは、Ｒ^１への結合数を表す。 A in the general formula (1) is a core molecular group of the phenylazomethine dendrimer, and the phenylazomethine dendrimer molecule is represented by B in the general formula (1) toward the outside centering on the core molecular group. Grow a chain of units to be played. As a result, the phenylazomethine dendrimer molecule after growth has a structure in which the B is linked and grown radially with the A at the center. The number of times B is linked is called a “generation”, and the generation adjacent to the core molecular group A is the first generation, and the number of generations increases toward the outside. A in the general formula (1) is the following formula:

R ¹ represents an aromatic group which may have a substituent, and p represents the number of bonds to R ¹ .

の構造で表され、Ｒ^２は、同一又は異なって置換基を有してもよい芳香族基を表す。このＢは、フェニルアゾメチンデンドリマーの世代を構成し、中核分子基Ａに直接結合するＢが第１世代となる。 B in the general formula (1) is the following formula that forms one azomethine bond with respect to A.

And R ² represents the same or different aromatic group which may have a substituent. This B constitutes the generation of phenylazomethine dendrimer, and B directly bonded to the core molecular group A is the first generation.

の構造で表され、Ｒ^３は、同一又は異なって置換基を有してもよい芳香族基を表す。Ｒは、フェニルアゾメチンデンドリマー分子の放射状に伸びた構造の末端に位置することになる。 R in the above general formula (1) is the following formula that forms an azomethine bond with B as a terminal group.

R ³ represents an aromatic group which may be the same or different and may have a substituent. R will be located at the end of the radially extended structure of the phenylazomethine dendrimer molecule.

In the general formula (1), n represents the number of generations of the phenylazomethine dendrimer through the structure B, m represents the number of terminal groups R of the phenylazomethine dendrimer, and when n = 0, m represents m. = P, and when n ≧ 1, m = 2 ⁿ p.

R ¹ , R ² and R ³ which are aromatic groups which may have a substituent each independently may be a phenyl group or a similar structure as the skeleton structure, for example, a phenyl group, biphenyl And various groups such as a group, a biphenylalkylene group, a biphenyloxy group, a biphenylcarbonyl group, and a phenylalkyl group. These skeletons are substituted with halogen atoms such as chlorine atom, bromine atom and fluorine atom, alkyl groups such as methyl group and ethyl group, haloalkyl groups such as chloromethyl group and trifluoromethyl group, methoxy group and ethoxy group. And various substituents such as alkoxyalkyl groups such as methoxyethyl groups, alkylthio groups, carbonyl groups, cyano groups, amino groups, and nitro groups. The skeleton can optionally have one or more of these substituents.

  Among the above substituents, substituents having high electron donating properties such as methoxy group and amino group, or substituents having high electron accepting properties such as cyano group and carbonyl group are preferable.

In the core part represented by the above formula R ¹ (—N =) _p , p is not particularly limited, and examples thereof include integers of 1 to 4. The generation number n of the phenylazomethine dendrimer is 0 or an integer of 1 or more, preferably 2 to 6, for example.

As one form of such a phenylazomethine dendrimer compound, a compound represented by the following formula can be exemplified. The compound represented by the following formula is a phenylazomethine dendrimer compound having a generation number of 4.

  When the phenylazomethine dendrimer compound represented by the above formula is mixed with a metal salt, the metal element coordinates to the nitrogen element of the phenylazomethine dendrimer compound and is taken into the phenylazomethine dendrimer compound. At this time, the metal element is coordinated preferentially to the nitrogen atom on the central portion side of the phenylazomethine dendrimer compound, and therefore coordinated in the order of the nitrogen atom existing on the central portion side to the nitrogen atom existing on the outside. Therefore, the metal element can be arranged at a desired position of the phenylazomethine dendrimer compound by controlling the molar ratio of the phenylazomethine dendrimer compound and the metal element.

  For example, an example in which 2 equivalents of a metal element are added to a phenylazomethine dendrimer compound represented by the above formula and an example in which 6 equivalents of a metal element are added are represented by the following formulas. In the following formula, the metal element coordinated with the phenylazomethine dendrimer compound is indicated by a black circle.

  As described above, in the phenyl azomethine dendrimer compound, the place where the metal element can coordinate is limited to a specific place, so the metal element coordinated to the phenyl azomethine dendrimer compound has a nano-level predetermined pitch. Will be placed. For this reason, by using a phenylazomethine dendrimer compound coordinated with a metal element as a catalyst, it is expected that the metal element having catalytic activity is utilized with high efficiency without aggregation. Further, by increasing or decreasing the number of generations of the phenylazomethine dendrimer compound, the upper limit number of metal elements that can be coordinated to one phenylazomethine dendrimer compound can be arbitrarily changed.

  A known method can be used to synthesize the above-mentioned phenylazomethine dendrimer. As such a method, for example, there is a method in which benzophenone and diaminobenzophenone are reacted in the presence of titanium chloride and a base in a chlorobenzene solvent and further reacted with diaminobenzophenone sequentially to increase the number of generations. There is no particular limitation.

  The metal element coordinated with the nitrogen-containing dendrimer compound is not particularly limited. Such a metal element is appropriately selected depending on the purpose of use of the metal element, such as use as a catalyst. Typical examples of the metal element coordinated to the nitrogen-containing dendrimer compound include titanium, vanadium, iron, cobalt, nickel, copper, zinc, gallium, zirconium, niobium, molybdenum, ruthenium, rhodium, palladium, silver, indium, tin, Examples include antimony, hafnium, tantalum, tungsten, osmium, iridium, platinum, gold, and bismuth.

[Organic solvent]
The organic solvent for dissolving the nitrogen-containing dendrimer compound is not particularly limited as long as it can dissolve a desired amount of the nitrogen-containing dendrimer compound and has a low miscibility with water. The solvent having low miscibility with water is not limited to a solvent that does not dissolve in water at all, and may be a solvent that dissolves in water to some extent. If a solvent that is poorly miscible with water is soluble in water to a certain degree, a solvent that is poorly miscible with water is an Any material can be used as long as it can form a two-phase system. The solvent having low miscibility with water has a solubility in water at 20 ° C. of preferably 1.0 g / 100 mL or less, and more preferably 0.9 g / 100 mL or less.

  Since the organic solvent is easily removed from the mixed solution of the organic solvent solution and the aqueous buffer solution by heating in the organic solvent removing step described later, the boiling point is lower than water or azeotropes with water. Organic solvents are preferred. Among such organic solvents, an organic solvent having a boiling point of 85 ° C. or lower is preferable, and an organic solvent having a boiling point of 75 ° C. or lower is more preferable. Further, the specific gravity of the organic solvent is preferably 1.2 or more, more preferably 1.4 or more. The specific gravity of the organic solvent is that when the density of water is 1. By using an organic solvent having such a boiling point and specific gravity, it becomes easy to remove the organic solvent in the organic solvent removing step described later. Specific examples of the organic solvent having low miscibility with water include chloroform, dichloroethane, and carbon tetrachloride, with chloroform being preferred.

[Method for preparing organic solvent solution of nitrogen-containing dendrimer compound]
The method for preparing the organic solvent solution of the nitrogen-containing dendrimer compound is not particularly limited as long as a predetermined amount of the nitrogen-containing dendrimer compound can be dissolved in the organic solvent. Usually, an organic solvent and a predetermined amount of a nitrogen-containing dendrimer compound are mixed and then stirred to dissolve the nitrogen-containing dendrimer compound in the organic solvent, whereby an organic solvent solution of the nitrogen-containing dendrimer compound is obtained. When the nitrogen-containing dendrimer compound is dissolved in an organic solvent, the organic solvent may be heated as necessary. Further, for the purpose of removing dissolved residue of nitrogen-containing dendrimer and insoluble impurities, an organic solvent solution of the nitrogen-containing dendrimer compound may be filtered with a filter having a desired opening diameter.

  The content of the nitrogen-containing dendrimer compound in the organic solvent solution of the nitrogen-containing dendrimer compound is not particularly limited as long as the object of the present invention is not impaired, but is preferably 1 to 20 μmol / L, and preferably 2.5 to 10 μmol / L. More preferred is 5-7.5 μmol / L.

<Mixing process>
In the mixing step, the organic solvent solution obtained in the dendrimer solution preparation step is mixed with an aqueous buffer containing a surfactant having a concentration of 5.0 × 10 ^{−4 to} 2.0 × 10 ⁻² mol / L. To do. In the dendrimer solution preparation step, a solvent having low miscibility with water is used. Therefore, the mixture solution containing the organic solvent solution and the aqueous buffer solution obtained in the mixing step is composed of an organic solvent phase and an aqueous phase. Form a phase system.

  The mixing ratio of the organic solvent solution and the aqueous buffer solution is not particularly limited as long as the desired aqueous dispersion of micelles of the nitrogen-containing dendrimer compound can be satisfactorily formed. Typically, the mixing ratio of the organic solvent solution and the aqueous buffer is preferably a volume ratio (organic solvent solution / aqueous buffer) of 0.2 / 0.8 to 0.8 / 0.2, 0 4 / 0.6 to 0.6 / 0.4 is more preferable. Hereinafter, the surfactant and the buffering agent contained in the aqueous buffer solution will be described.

[Surfactant]
The surfactant contained in the aqueous buffer solution is not particularly limited as long as an aqueous dispersion of micelles of a nitrogen-containing dendrimer compound can be satisfactorily formed. Anionic surfactants, cationic surfactants, and nonionic surfactants Any of these can be used. Among the surfactants, it is preferable to use a cationic surfactant.

又は下記一般式（ＩＩ）

で表される基であり、Ｒ^４、Ｒ^５、及びＲ^６は、それぞれ、炭素数１〜３のアルキル基であり、Ｒ^７、Ｒ^８、Ｒ^９、Ｒ^１０、及びＲ^１１は、それぞれ、炭素数１又は２のアルキル基であり、Ｘはハロゲン原子である。） Among such surfactants, the compound represented by the following general formula (2) is preferable because the nitrogen-containing dendrimer compound is easily incorporated into the aqueous dispersion of micelles of the nitrogen-containing dendrimer compound with high efficiency.
^{_{Y-O- (CH 2) q}} -Q r + · rX - ··· (2)
(In General Formula (2), Y is a phenyl group which may have a substituent or a naphthyl group which may have a substituent, q is an integer of 10 to 14, and r is 1 or 2. Yes, Q ^{r +} is the following general formula (I):

Or the following general formula (II)

R ⁴ , R ⁵ , and R ⁶ are each an alkyl group having 1 to 3 carbon atoms, and R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , and R ¹¹ are each , An alkyl group having 1 or 2 carbon atoms, and X is a halogen atom. )

The compound represented by the general formula (2) is, for example, the following general formula (III)
Y-OH (III)
(In general formula (III), Y is the same as in general formula (2).)
A hydroxyaryl compound represented by the following general formula (IV):
_{X- (CH 2) q -X ···} (IV)
(In general formula (IV), q is the same as in general formula (2), and X is a halogen atom.)
Is reacted with an alkyl dihalide represented by the following general formula (V):
_{Y-O- (CH 2) q} -X ··· (V)
(In general formula (V), Y and q are the same as those in general formula (2), and X is a halogen atom.)
After synthesizing the aryloxyalkyl halide represented by the formula (V), the aryloxyalkyl halide represented by the general formula (V) is converted into a tertiary amino group represented by the general formulas (I) and (II). It can be produced by reacting with an amine compound.

  In the compound represented by the general formula (2), Y is a phenyl group which may have a substituent, or a naphthyl group which may have a substituent. Examples of the substituent that Y may have include an alkyl group having 1 to 4 carbon atoms such as a methyl group, an ethyl group, an n-propyl group, and an isopropyl group; a vinyl group, a 1-propenyl group, and an allyl group. C2-C4 alkenyl group; C2-C4 alkynyl group such as ethynyl group, 1-propynyl group and 2-propynyl group; methoxy group, ethoxy group, n-propoxy group, isopropoxy group and the like Examples thereof include an alkoxy group having 1 to 4 carbon atoms; a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom and an iodine atom; an amino group; and a nitro group. In the compound represented by the general formula (2), Y is preferably an unsubstituted phenyl group or a naphthalen-2-yl group.

In the compound represented by the general formula (2), specific examples of the alkylene group represented by — (CH ₂ ) _q — include decane-1,10-diyl group, undecane-1,11-diyl group, and dodecane. Examples include -1,12-diyl group, tridecane-1,13-diyl group, and tetradecane-1,14-diyl group.

Specific examples of R ⁴ , R ⁵ , and R ⁶ in the general formula (I) include a methyl group, an ethyl group, an n-propyl group, and an isopropyl group. As the group represented by the general formula (I), a group in which R ⁴ , R ⁵ and R ⁶ are all ethyl groups is preferable.

Specific examples of R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , and R ^{11 in} the general formula (II) include a methyl group and an ethyl group.

  Specific examples of X that is a halogen atom in the general formula (2), the general formula (IV), and the general formula (V) include a chlorine atom, a bromine atom, and an iodine atom.

The concentration of the surfactant in the aqueous buffer is 5.0 × 10 ^{−4 to} 2.0 × 10 ⁻² mol / L.

[Buffer]
The buffer contained in the aqueous buffer is not particularly limited, and a buffer contained in buffers conventionally used for various purposes can be used. As the buffer, any of metal-containing buffers such as sodium phosphate and potassium salts of phosphate and metal-free buffers can be used. When an aqueous dispersion of micelles containing nitrogen-containing dendrimer compounds is applied and used, the metal salt does not precipitate, and the resulting aqueous dispersion of micelles containing nitrogen-containing dendrimer compounds is a biological material derived from organisms such as animals and plants. A metal-free buffering agent is preferable because it can be easily applied to the above-described treatment.

  Specific examples of the metal-free buffer include Tris (tris (hydroxymethyl) aminomethane), HEPES (4- (2-hydroxyethyl) -1-piperazineethanesulfonic acid), ACES (N-2- (acetamide) ) -2-aminoethanesulfonic acid), MES (2-morpholinoethanesulfonic acid), ADA (N- (2-acetamido) iminodiacetic acid), PIPES (piperazine-1,4-bis (2-ethanesulfonic acid)) , Collamine hydrochloride (N, N, N-trimethyl-2-aminoethaneaminium chloride), BES (N, N-bis (2-hydroxyethyl) -2-aminoethanesulfonic acid), TES (N-tris (hydroxy) Methyl) methyl-2-aminoethanesulfonic acid), acetamidoglycine, tricine (N- [tris (hydroxy Chill) methyl] glycine), glycinamide, and Bicine (2- bis (2-hydroxyethyl) amino acid), TMAH (tetramethyl amine hydroxide), and include hydrochloride.

  The concentration of the buffering agent in the aqueous buffer is not particularly limited and is appropriately selected according to the type of the buffering agent so that the aqueous buffer has a desired pH. Typically, the pH of the aqueous buffer is preferably 6.6 to 8.5.

<Organic solvent removal step>
In the organic solvent removal step, the organic solvent is removed from the mixed solution of the organic solvent solution of the nitrogen-containing dendrimer compound obtained in the mixing step and the aqueous buffer solution. By removing the organic solvent from the mixed solution, the nitrogen-containing dendrimer compound is transferred from the organic solvent solution to the aqueous buffer solution with a decrease in the amount of the organic solvent in the mixed solution. When the nitrogen-containing dendrimer compound is transferred to the aqueous buffer solution, the aqueous buffer solution contains a surfactant. Therefore, the surfactant is collected on the surface of the nitrogen-containing dendrimer, and micelles centering on the nitrogen-containing dendrimer compound are formed.

  In the organic solvent removal step, the method for removing the organic solvent from the mixed solution is not particularly limited. As a suitable method for removing the organic solvent from the mixed solution, there is a method in which the mixed solution is heated to the boiling point of the organic solvent or the azeotropic point of the organic solvent and water to distill off the organic solvent from the mixed solution. When the mixture is heated to distill off the organic solvent, the mixture may be heated under reduced pressure for the purpose of lowering the heating temperature.

  When the organic solvent and water azeotrope, a condenser capable of separating the condensate is attached to the line where the mixed vapor of the organic solvent and water distills, and the aqueous phase separated from the condensate is returned to the mixture. However, the organic solvent may be removed. Moreover, when an organic solvent and water azeotrope, you may remove an organic solvent, adding the water of a substantially equivalent quantity to the water distilled with an organic solvent to a liquid mixture. When the organic solvent and water azeotrope, as described above, the concentration of the aqueous dispersion of micelles of the resulting nitrogen-containing dendrimer compound becomes excessively high by removing the organic solvent while adding water to the mixture. Can be prevented.

  Although removal of the organic solvent can be stopped in a state where the organic solvent remains in the mixed solution, 98% by mass or more of the organic solvent is removed from the mixed solution from the viewpoint of effective use of the nitrogen-containing dendrimer compound. It is preferable to remove 99% by mass or more, and it is most preferable to remove 100% by mass. When the organic solvent remains in the mixed solution after the organic solvent removing step, the organic solvent phase may be removed from the mixed solution by a method such as liquid separation.

  The aqueous dispersion of micelles of nitrogen-containing dendrimer compounds obtained by removing the organic solvent from the mixed solution may be hydrated or concentrated as necessary to adjust the concentration of micelles of nitrogen-containing dendrimer compounds.

  According to the method of the present invention described above, an aqueous dispersion of micelles of a nitrogen-containing dendrimer compound can be produced by solubilizing the nitrogen-containing dendrimer compound with high efficiency in water. The aqueous dispersion of micelles of a nitrogen-containing dendrimer compound produced by the method of the present invention can be applied to various uses such as catalyst materials, electronic materials, and luminescent materials.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to these Examples.

In Examples 1 and 2, a compound represented by the following formula (DPAG4er) was used as the phenylazomethine dendrimer compound.

で表される界面活性剤（ＢＭＮ）を５．０ｍＭ濃度で含み、ｐＨ６．８６であるリン酸塩緩衝液１ｍｌを加えた。クロロホルム溶液と、緩衝液との混合液から、１５０ｍｍＨｇ、２５℃の条件でクロロホルムをゆっくり除去して、ＤＰＡＧ４ｅｒのミセルの水性分散液を得た。得られた水性分散液を移した後の容器に再度クロロホルムを加えて、デンドリマーによる着色を観察したところ、着色は観察されなかった。 [Example 1]
DPAG4er was dissolved in 1 ml of chloroform to obtain a DPAG4er chloroform solution having a DPAG4er concentration of 5 μM. In the resulting chloroform solution,

1 ml of a phosphate buffer containing a surfactant (BMN) represented by the formula (5) at a concentration of 5.0 mM and having a pH of 6.86 was added. Chloroform was slowly removed from the mixed solution of the chloroform solution and the buffer under conditions of 150 mmHg and 25 ° C. to obtain an aqueous dispersion of micelles of DPAG4er. Chloroform was added again to the container after the obtained aqueous dispersion was transferred, and when coloring with a dendrimer was observed, no coloring was observed.

[Example 2]
An aqueous dispersion of DPAG4er micelles was prepared in the same manner as in Example 1 except that the buffer contained in the buffer was changed from phosphate to Tris, ACES, or HEPES. Chloroform was added again to the container after transferring the aqueous dispersion obtained in the same manner as in Example 1, and when coloring with a dendrimer was observed, no coloring was observed.

で表される含窒素デンドリマー化合物と、界面活性剤（ＢＭＮ）とをクロロホルム１ｍｌに溶解させて、含窒素デンドリマー化合物の濃度が５μＭであり、界面活性剤の濃度が１０ｍＭである含窒素デンドリマー化合物のクロロホルム溶液を得た。得られたクロロホルム溶液に、ｐＨ６．８６のリン酸塩緩衝液２ｍｌを加えた。クロロホルム溶液と、緩衝液との混合液から、実施例１と同様にしてクロロホルムを除去して、含窒素デンドリマー化合物のミセルの水性分散液を得た。得られた水性分散液の吸光度を測定して、含窒素デンドリマー化合物の可溶化率を求めたところ５４％であった。
また、実施例１と同様にして得られた水性分散液を移した後の容器に再度クロロホルムを加えて、デンドリマーによる着色を観察したところ、黄色の着色が観察された。 [Comparative Example 1]
The following formula

The nitrogen-containing dendrimer compound represented by the formula (1) and a surfactant (BMN) are dissolved in 1 ml of chloroform, the concentration of the nitrogen-containing dendrimer compound is 5 μM, and the concentration of the surfactant is 10 mM. A chloroform solution was obtained. To the resulting chloroform solution was added 2 ml of pH 6.86 phosphate buffer. Chloroform was removed from the mixed solution of the chloroform solution and the buffer solution in the same manner as in Example 1 to obtain an aqueous dispersion of micelles of a nitrogen-containing dendrimer compound. The absorbance of the obtained aqueous dispersion was measured, and the solubilization rate of the nitrogen-containing dendrimer compound was determined to be 54%.
In addition, chloroform was added again to the container after the aqueous dispersion obtained in the same manner as in Example 1 was transferred, and the coloration by the dendrimer was observed. As a result, yellow coloration was observed.

  According to Examples 1 and 2, most of the nitrogen-containing dendrimer remains in the container used for preparing the aqueous dispersion after the aqueous dispersion is transferred from the container used for preparing the aqueous dispersion to another container. From this, it can be seen that the nitrogen-containing dendrimer compound is well solubilized in water. On the other hand, in Comparative Example 1, after the aqueous dispersion was transferred from the container used for the preparation of the aqueous dispersion to another container, the nitrogen-containing dendrimer remained in the container used for the preparation of the aqueous dispersion. The solubilization rate of nitrogen dendrimers in water is low.

Claims (3)

A dendrimer solution preparation step of preparing an organic solvent solution of a nitrogen-containing dendrimer compound by dissolving a nitrogen-containing dendrimer compound having at least one nitrogen atom to which a metal element can coordinate, in a solvent having low miscibility with water;
A mixing step of mixing the organic solvent solution and an aqueous buffer containing a surfactant having a concentration of 5.0 × 10 ^{−4 to} 2.0 × 10 ⁻² mol / L;
The manufacturing method of the aqueous dispersion of the micelle of a nitrogen-containing dendrimer compound including the organic-solvent removal process of removing an organic solvent from the liquid mixture of the said organic-solvent solution and the said aqueous buffer. The method for producing an aqueous dispersion of micelles of a nitrogen-containing dendrimer compound according to claim 1, wherein the nitrogen-containing dendrimer compound is a phenylazomethine dendrimer compound represented by the following general formula (1).

(A in the above general formula (1) is a core molecular group of phenylazomethine dendrimer,

Wherein R ¹ represents an aromatic group which may have a substituent, and p represents the number of bonds to R ¹ ;
B in the above general formula (1) is the following formula that forms one azomethine bond to A.

R ² represents an aromatic group which may be the same or different and may have a substituent;
R in the above general formula (1) is the following formula that forms an azomethine bond with B as a terminal group.

R ³ represents an aromatic group which may be the same or different and may have a substituent;
n represents the number of generations of the phenylazomethine dendrimer through the B structure;
m represents the number of terminal groups R of the phenylazomethine dendrimer. When n = 0, m = p, and when n ≧ 1, m = 2 ⁿ p. ) The manufacturing method of the aqueous dispersion of the micelle of the nitrogen-containing dendrimer compound of Claim 1 or 2 whose said surfactant is a compound represented by following General formula (2).
^{_{Y-O- (CH 2) q}} -Q r + · rX - ··· (2)
(In the general formula (2), Y is a phenyl group which may have a substituent or a naphthyl group which may have a substituent, q is an integer of 10 to 14, and r is 1 or 2) And Q ^{r +} is the following general formula (I):

Or the following general formula (II)

R ⁴ , R ⁵ , and R ⁶ are each an alkyl group having 1 to 3 carbon atoms, and R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , and R ¹¹ are each , An alkyl group having 1 or 2 carbon atoms, and X is a halogen atom. )