JP2013230954A - Method for producing mesoporous silica - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a convenient method for producing mesoporous silica with large specific surface area, suitable to adsorptive separation of protein or the like and to applications of DDS (drug delivery system).SOLUTION: A production method of mesoporous silica includes a first step of preparing a silica precursor aqueous solution by dissolving alkoxysilane into an acidic aqueous solution; a second step of preparing a block copolymer solution by dissolving a block copolymer (Z) into an organic solvent, where the block copolymer (Z) including a hydrophilic polymer block (S) containing a structural unit derived from an aromatic vinyl compound and having a sulfonate group, and a hydrophobic polymer block (T) comprising an amorphous polymer containing a structural unit derived from an unsaturated hydrocarbon compound, as structural components; a third step of mixing the silica precursor aqueous solution and the block copolymer solution; a fourth step of obtaining a solid content by removing the organic solvent and water from the mixed liquid obtained in the third step; and a fifth step of firing the solid content obtained in the fourth step.

Description

  The present invention relates to a method for producing mesoporous silica, and more particularly to a method for producing mesoporous silica useful for adsorption separation of proteins, drug delivery systems, and the like.

  In recent years, research on porous silica has been conducted. In particular, porous silica having pores with a pore diameter of 2 to 50 nm is called mesoporous silica, and its use for adsorption separation of proteins and drug delivery systems (DDS) is being studied. In these applications, mesoporous silica having a large specific surface area is considered desirable.

  In general, porous silica is produced using a micelle dispersion in which a surfactant is dispersed in an aqueous solvent. The surfactant has a hydrophilic part and a hydrophobic part, and in an aqueous solvent, the diameter is uniform (that is, the particle diameters are uniform) with the hydrophilic part oriented outward and the hydrophobic part oriented inward. ) Spherical micelles are formed and dispersed uniformly. When various silica precursors described later are mixed with the micelle dispersion and the solvent is removed, an organic-inorganic composite in which the surfactant is uniformly dispersed in the silica precursor is formed, and the surfactant is removed by firing. At the same time, silica is produced to obtain mesoporous silica.

  For example, a silica precursor obtained by treating sodium silicate with an acidic solvent is mixed with a cationic surfactant such as a long-chain alkylammonium halide to obtain mesoporous silica powder having a pore diameter of 2 to 5 nm. Is known (see Patent Document 1).

  In addition, the silica precursor obtained from the hydrolysis reaction of alkoxysilane is mixed with a nonionic triblock copolymer having a propylene oxide polymer block between two ethylene oxide polymer blocks, thereby reducing the pore diameter. It is known that 5-26 nm mesoporous silica is obtained (see Patent Document 2).

  Further, a method is known in which mesoporous silica having a pore surface diameter of about 30 nm and a high specific surface area is obtained using a block copolymer of a styrene polymer block and an ethylene oxide polymer block (see Non-Patent Document 1). Furthermore, production of a thin film made of mesoporous silica having spherical pores with a pore diameter of about 10 nm has been reported (see Non-Patent Document 2).

JP-A-8-259220 Japanese translation of PCT publication No. 2003-531083

Journal of American Chemical Society (J. of Am. Chem. Soc.), 1690 (2007). Advanced Functional Materials (Adv. Funct. Mater.), 47 (2003).

  Since mesoporous silica having a pore diameter of 2 to 5 nm described in Patent Document 1 has a relatively small pore diameter, its application is limited. Moreover, in order to obtain mesoporous silica by the method described in Patent Document 2, an organic swelling agent is added to a solution of a silica precursor and a nonionic triblock copolymer, and the reaction solution is heated to a high temperature (100 to 140 ° C. ) For a long time (11 to 72 hours). Further, in the method described in Non-Patent Document 1, in order to increase the specific surface area, it is necessary to heat the produced mesoporous silica in water at a higher temperature (100 ° C.) for a long time (72 hours). A thin film made of mesoporous silica obtained by the method described in Non-Patent Document 2 has a small specific surface area.

  Accordingly, an object of the present invention is to provide an industrially advantageous production method capable of producing mesoporous silica having a large specific surface area suitable for adsorption separation of proteins and the like and DDS applications at a low temperature in a short time.

In order to achieve the above object, the present invention provides:
A first step of preparing an aqueous silica precursor solution by dissolving an alkoxysilane in an acidic aqueous solution;
Hydrophobic polymer comprising a hydrophilic polymer block (S) having a structural unit derived from an aromatic vinyl compound and having a sulfonic acid group, and an amorphous polymer containing a structural unit derived from an unsaturated hydrocarbon compound A second step of preparing a block copolymer solution by dissolving the block copolymer (Z) having the combined block (T) as a constituent component in an organic solvent;
A third step of mixing the silica precursor aqueous solution and the block copolymer solution;
A mesoporous solution comprising: a fourth step of obtaining a solid content by removing an organic solvent and water from the mixed solution obtained in the third step; and a fifth step of firing the solid content obtained in the fourth step. A method for producing silica is provided.

  According to the present invention, mesoporous silica suitable for adsorption separation of proteins and the like and DDS applications can be produced at low temperature in a short time, which is industrially advantageous.

It is an X-ray diffraction pattern by GI-SAXS after baking of the mesoporous silica obtained in Examples 1, 2, and 4. It is a scanning electron micrograph of the mesoporous silica obtained in Examples 1-6, FIG. A is Example 1, FIG. B is Example 2, FIG. C is Example 3, FIG. D is Example 4, FIG. Is Example 5, and FIG. FIG. 2 is a transmission electron micrograph of mesoporous silica obtained in Examples 2 and 5. FIG. A is Example 2 and FIG. It is a nitrogen adsorption isotherm of the mesoporous silica obtained in Examples 1-6. In FIG. (A), A is Example 1, B is Example 2, C is Example 3, and in FIG. (B). , D is Example 4, E is Example 5, and F is Example 6. It is a pore distribution curve of the mesoporous silica obtained in Examples 1-6. In the figure, A is Example 1, B is Example 2, C is Example 3, D is Example 4, and E is Example. 5 and F are Example 6.

Hereinafter, the present invention will be described in detail with reference to preferred embodiments thereof.
The method for producing the mesoporous silica of the present invention comprises:
1st process: The process which dissolves alkoxysilane in acidic aqueous solution, and prepares silica precursor aqueous solution;
2nd process: From the amorphous polymer containing the structural unit derived from the hydrophilic polymer block (S) which has a structural unit derived from an aromatic vinyl compound, and has a sulfonic acid group, and an unsaturated hydrocarbon compound A step of preparing a block copolymer solution by dissolving a block copolymer (Z) comprising a hydrophobic polymer block (T) as a constituent component in an organic solvent;
3rd process: The process of mixing a silica precursor aqueous solution and a block copolymer solution;
Fourth step: a step of removing the organic solvent and water from the liquid mixture obtained in the third step to obtain a solid content; and a fifth step: a step of firing the solid content obtained in the fourth step; Including at least.

[First step]
By dissolving the alkoxysilane in the acidic aqueous solution, the alkoxyl group (—OR) of the alkoxysilane is hydrolyzed and converted into a hydroxyl group (—OH) in the acidic aqueous solution, and further dehydrated and condensed to have a high molecular weight. Presumed to be a silica precursor.
As alkoxysilane, what is shown, for example by following General formula (1) can be used.

(In the formula, R represents an alkyl group, Y represents a hydrogen atom, a halogen atom, a hydroxyl group or a hydrocarbon group, and n represents an integer of 1 or more and 4 or less.)

  The alkyl group represented by R in the general formula (1) is not particularly limited, and may be linear or branched. An alkyl group having 1 to 5 carbon atoms is preferable, and a methyl group or an ethyl group is more preferable. The hydrocarbon group represented by Y is, for example, an alkyl group having 1 to 10 carbon atoms such as a methyl group; an alkenyl group having 2 to 10 carbon atoms such as an allyl group; an aryl group such as a phenyl group or an alkyl-substituted phenyl group; An aralkyl group such as a benzyl group; Moreover, as a halogen atom which Y represents, a fluorine atom, a chlorine atom, and a bromine atom are preferable.

  When n is 2 to 4, n (OR) s may be the same or different, but are preferably the same. n is preferably 3 or 4. When (4-n) is 2 or more, the plurality of Y may be the same or different.

  Among the alkoxysilanes represented by the general formula (1), mesoporous silica having good crystallinity can be obtained. (Alternative name: tetraethoxysilane) and triethoxymethylsilane are preferred.

  An alkoxysilane may be used individually by 1 type, or may use 2 or more types together.

  Examples of the acidic aqueous solution used in the first step include aqueous solutions of inorganic acids such as hydrochloric acid, nitric acid, boric acid, bromic acid, fluoric acid, sulfuric acid, and phosphoric acid. You may use the above together. The pH of the acidic aqueous solution is preferably 3 or less, more preferably 2 or less, from the viewpoint of smoothly proceeding the hydrolysis reaction of alkoxysilane. Moreover, you may contain organic substances, such as alcohol, in the range which does not inhibit the said hydrolysis reaction.

  In the first step, the alkoxysilane is preferably dissolved in the acidic aqueous solution with stirring, and the temperature at the time of dissolution is preferably in the range of 0 to 80 ° C, more preferably in the range of 5 to 50 ° C. More preferably, the temperature is in the range of 10 to 30 ° C. The preparation time required for the alkoxysilane to dissolve in the acidic aqueous solution is usually in the range of 1 to 90 minutes. The first step is preferably performed in an air atmosphere.

[Second step]
In the second step, the hydrophilic polymer block (S) having a sulfonic acid group containing a structural unit derived from an aromatic vinyl compound (hereinafter referred to as “a sulfonic acid group containing a structural unit derived from an aromatic vinyl compound. Hydrophilic polymer block (S) ”is simply referred to as“ hydrophilic polymer block (S) ”), and an amorphous polymer containing a structural unit derived from an unsaturated hydrocarbon compound. Combined block (T) (hereinafter, “hydrophobic polymer block (T) which is an amorphous polymer containing a structural unit derived from an unsaturated hydrocarbon compound” is simply referred to as “hydrophobic polymer block (T)”. A block copolymer solution is prepared by dissolving a block copolymer (Z) having a component as a constituent in an organic solvent. In the block copolymer solution, the block copolymer (Z) forms micelles of equal diameter with the hydrophilic polymer block (S) oriented outward and the hydrophobic polymer block (T) oriented inward. Are considered to be evenly distributed.

  In the second step, as an organic solvent for dissolving the block copolymer (Z), from the viewpoint of forming stable micelles, methanol, ethanol, n-propanol, 2-propanol, 2-methyl-1-propanol, etc. Preference is given to alcohols; ethers such as tetrahydrofuran (THF); polar organic solvents such as ketones such as acetone and cyclohexanone. These polar organic solvents may be used alone or in combination of two or more. Moreover, you may use nonpolar organic solvents, such as toluene, mixing with a polar organic solvent in order to improve the solubility of a block copolymer (Z). Among the above organic solvents, THF, a mixed solvent of THF and ethanol, a mixed solvent of THF and n-propanol, a cyclohexanone, a mixed solvent of cyclohexanone and ethanol, toluene and 2 from the high miscibility with the aqueous silica precursor solution. A mixed solvent of -propanol, a mixed solvent of toluene and 2-methyl-1-propanol, and the like are preferable.

  The second step is preferably performed in an air atmosphere. A block copolymer solution can be prepared by adding the organic solvent to the block copolymer (Z) and stirring usually for 30 minutes to 3 hours. The preparation temperature is not particularly limited as long as the block copolymer (Z) is not decomposed. From the viewpoint of increasing the dissolution rate of the block copolymer (Z), a range of 25 to 100 ° C. is preferable, and 40 to 70 is preferable. A range of ° C is more preferred.

  The solid content concentration of the prepared block copolymer solution is preferably 0.5 to 30% by mass, and more preferably 1 to 20% by mass. If it is lower than 0.5% by mass, the productivity tends to be poor, and if it is higher than 30% by mass, the viscosity of the resulting block copolymer solution may increase and handling may be difficult. The viscosity of the block copolymer solution to be prepared is, for example, preferably 20 Pa · s or less, and more preferably 10 Pa · s or less. When the viscosity of the block copolymer solution exceeds 20 Pa · s, handling tends to be difficult.

Hereinafter, the block copolymer (Z) will be described.
<Hydrophilic polymer block (S)>
The hydrophilic polymer block (S) which is a constituent component of the block copolymer (Z) is a polymer block (S ₀ ) (hereinafter referred to as a polymer block containing a structural unit derived from an aromatic vinyl compound and having no sulfonic acid group). The “polymer block (S ₀ ) containing a structural unit derived from an aromatic vinyl compound and having no sulfonic acid group” is simply referred to as “polymer block (S ₀ )”). It is obtained by introducing. The aromatic ring of the aromatic vinyl compound is preferably a carbocyclic aromatic ring, and examples thereof include a benzene ring, a naphthalene ring, an anthracene ring, and a pyrene ring.

Examples of the monomer capable of forming the polymer block (S ₀ ) include styrene, 2-methylstyrene, 3-methylstyrene, 4-methylstyrene, 4-ethylstyrene, 2,4-dimethylstyrene, 2,5. -Aromatic vinyl compounds such as dimethyl styrene, 3,5-dimethyl styrene, 2-methoxy styrene, 3-methoxy styrene, 4-methoxy styrene, vinyl biphenyl, vinyl terphenyl, vinyl naphthalene, vinyl anthracene, 4-phenoxy styrene, etc. Can be mentioned.

  Further, in the aromatic vinyl compound, the α-position carbon (α-carbon) of the aromatic ring may be a quaternary carbon. When the α-carbon is a quaternary carbon, examples of the substituent bonded to the α-carbon include an alkyl group having 1 to 4 carbon atoms (methyl group, ethyl group, n-propyl group, isopropyl group, n- A butyl group, an isobutyl group, a sec-butyl group, or a tert-butyl group), a halogenated alkyl group having 1 to 4 carbon atoms (chloromethyl group, 2-chloroethyl group, 3-chloroethyl group, etc.), and a phenyl group. Can do. As the aromatic vinyl compound having the substituent, α-methylstyrene, α-methyl-4-methylstyrene, α-methyl-4-ethylstyrene, and 1,1-diphenylethylene are preferable.

From the viewpoint of introducing an aromatic ring sulfonic acid groups of the polymer block S _0, it is on the aromatic ring of the aromatic vinyl compound is desirably no functional groups which interfere with the reaction of introducing a sulfonic acid group. For example, if hydrogen on the aromatic ring of styrene (particularly hydrogen at the 4-position) is substituted with an alkyl group (particularly an alkyl group having 3 or more carbon atoms) or the like, it may be difficult to introduce a sulfonic acid group. It is preferable that the aromatic ring is not substituted with another functional group, or is substituted with a substituent capable of introducing a sulfonic acid group itself, such as an aryl group. Styrene, α-methylstyrene, 4-methylstyrene, 4-ethylstyrene, and vinylbiphenyl are more preferable from the viewpoint of increasing the density of the group.

The polymer block (S ₀ ) may contain a structural unit derived from one or more other monomers other than the aromatic vinyl compound as long as the effects of the present invention are not impaired. Examples of such other monomers include conjugated dienes having 4 to 8 carbon atoms (1,3-butadiene, 1,3-pentadiene, isoprene, 1,3-hexadiene, 2,4-hexadiene, 2,3- Dimethyl-1,3-butadiene, 2-ethyl-1,3-butadiene, 1,3-heptadiene, etc.), alkenes having 2 to 8 carbon atoms (ethylene, propylene, 1-butene, 2-butene, isobutene, 1- Pentene, 2-pentene, 1-hexene, 2-hexene, 1-heptene, 2-heptene, 1-octene, 2-octene, etc.), (meth) acrylic acid esters (methyl (meth) acrylate, (meth) acrylic) Ethyl acetate, butyl (meth) acrylate, etc.), vinyl esters (vinyl acetate, vinyl propionate, vinyl butyrate, vinyl pivalate, etc.), vinyl ether (methyl) Vinyl ether, isobutyl vinyl ether, etc.), and the like. The copolymerization form of the aromatic vinyl compound and the other monomer is desirably random copolymerization. These other monomers are preferably 10% by mass or less, more preferably 5% by mass or less of the monomer capable of forming the polymer block (S ₀ ).

The number average molecular weight per polymer block (S ₀ ) is preferably in the range of 1,000 to 50,000 as the number average molecular weight in terms of standard polystyrene measured by gel permeation chromatography (GPC) method, The range of 3,000 to 40,000 is more preferable, and the range of 5,000 to 25,000 is more preferable. When the number average molecular weight is less than 1,000 or exceeds 50,000, it may be difficult to form micelles of the block copolymer (Z) derived from the block copolymer (Z ₀ ).

In order to obtain mesoporous silica with small variations in pore diameter with good reproducibility, the amount of sulfonic acid groups introduced into the polymer block (S ₀ ) is important. In the production of the mesoporous silica of the present invention, the equivalent number of sulfonic acid groups per unit mass of the block copolymer (Z) (hereinafter referred to as “ion exchange capacity”) is preferably 0.10 meq / g or more, It is more preferably 0.30 meq / g or more, and particularly preferably 0.75 meq / g or more. The upper limit of the ion exchange capacity is preferably 5.00 meq / g or less because mesoporous silica cannot be obtained with good reproducibility because the balance of hydrophilicity / hydrophobicity is lost if the ion exchange capacity becomes too large. It is more preferably 2.5 meq / g or less, and further preferably 1.1 meq / g or less. The ion exchange capacity of the sulfonated block copolymer (Z) can be calculated using an acid value titration method.

<Hydrophobic polymer block (T)>
The hydrophobic polymer block (T) which is a constituent component of the block copolymer (Z) is an amorphous polymer block containing a structural unit derived from an unsaturated hydrocarbon compound. Here, “amorphous” can be confirmed by measuring the dynamic viscoelasticity of the block copolymer (Z) and confirming that there is no change in the storage elastic modulus derived from the crystalline olefin polymer.

  The monomer capable of forming the hydrophobic polymer block (T) is not particularly limited as long as it is an unsaturated hydrocarbon compound having a polymerizable carbon-carbon double bond, but is preferably a chain unsaturated hydrocarbon compound, For example, an olefin having 2 to 8 carbon atoms (ethylene, propylene, 1-butene, 2-butene, isobutene, 1-pentene, 2-pentene, 1-hexene, 2-hexene, 1-heptene, 2-heptene, 1- Octene, 2-octene, etc.), conjugated diene compounds having 4 to 8 carbon atoms (1,3-butadiene, 1,3-pentadiene, isoprene, 1,3-hexadiene, 2,4-hexadiene, 2,3-dimethyl- 1,3-butadiene, 2-ethyl-1,3-butadiene, 1,3-heptadiene, etc.). When the monomer has a plurality of polymerizable carbon-carbon double bonds, any of them may be used for polymerization. For example, in the case of a conjugated diene compound, a 1,2-bond may be used. , 4-bonds or these may be mixed.

  The said monomer which can form a hydrophobic polymer block (T) may be used individually by 1 type, or may use 2 or more types together. When using 2 or more types together, it is preferable that the arrangement | sequence of the structural unit which comprises a hydrophobic polymer block (T) is random.

  Further, the hydrophobic polymer block (T) may contain a structural unit derived from another monomer within the range not impairing the effects of the present invention, in addition to the monomer. Examples of such other monomers include aromatic vinyl compounds such as styrene and vinyl naphthalene, halogen-containing vinyl compounds such as vinyl chloride, vinyl esters (vinyl acetate, vinyl propionate, vinyl butyrate, vinyl pivalate, etc.), vinyl ethers. (Methyl vinyl ether, isobutyl vinyl ether, etc.) and the like. In this case, the arrangement of the structural units forming the hydrophobic polymer block (T) is preferably random. The structural unit derived from the other monomer is preferably 5% by mass or less of the hydrophobic polymer block (T).

  If the number average molecular weight per polymer block (T) is too small, the stability of the micelle tends to decrease, and if too large, the pore diameter is expanded and the adsorption amount of proteins and drugs tends to decrease. . For this reason, the number average molecular weight in terms of standard polystyrene measured by gel permeation chromatography (GPC) is preferably in the range of 3,000 to 150,000, more preferably in the range of 20,000 to 100,000. The range of 5,000 to 75,000 is more preferable.

<Block copolymer (Z)>
The block copolymer (Z) has at least one hydrophilic polymer block (S) and one hydrophobic polymer block (T). In the case of having a plurality of hydrophilic polymer blocks (S), their structures (type of monomer constituting, degree of polymerization, type of sulfonic acid group, introduction ratio, etc.) may be the same or different from each other. It may be. Moreover, when it has two or more hydrophobic polymer blocks (T), those structures (a kind of monomer to comprise, a polymerization degree, etc.) may mutually be the same, and may differ.

  As an example of the arrangement of the hydrophilic polymer block (S) and the hydrophobic polymer block (T) in the block copolymer (Z), an S-T type diblock copolymer (S and T are respectively hydrophilic Reactive polymer block (S), hydrophobic polymer block (T)), STS type triblock copolymer, TST type triblock copolymer, STS type Examples thereof include a triblock copolymer or a mixture of a TST type triblock copolymer and a S type diblock copolymer. In the mesoporous silica of the present invention, these block copolymers may be used alone or in combination of two or more.

  In the block copolymer (Z) forming the mesoporous silica of the present invention, the ratio of the total amount of the hydrophilic polymer block (S) and the total amount of the hydrophobic polymer block (T) is expressed in mass ratio. The ratio is preferably 10:90 to 50:50, and more preferably 20:80 to 40:60 from the viewpoint of reproducible mesoporous silica having a small variation in pore diameter.

<Production of block copolymer (Z ₀ )>
The block copolymer (Z) for forming the mesoporous silica of the present invention is prepared by producing a block copolymer (Z ₀ ) comprising a polymer block (S ₀ ) and a hydrophobic polymer block (T), A method of introducing a sulfonic acid group into the combined block (S ₀ ) can be used.

The production method of the block copolymer (Z ₀ ) is appropriately selected from radical polymerization method, anion polymerization method, cationic polymerization method, coordination polymerization method, etc. depending on the kind of monomer constituting, molecular weight, etc. The radical polymerization method, the anionic polymerization method, or the cationic polymerization method is preferably selected from the viewpoint of practical ease. In particular, a so-called living polymerization method is preferable from the viewpoint of molecular weight, molecular weight distribution, and the like, and specifically, a living radical polymerization method, a living anion polymerization method, and a living cation polymerization method are preferable.

As a specific example of the method for producing a block copolymer (Z ₀ ) composed of a polymer block (S ₀ ) and a hydrophobic polymer block (T), the polymer block (S ₀ ) is styrene, α-methylstyrene, A method for producing a block copolymer (Z ₀ ) formed from an aromatic vinyl compound such as t-butylstyrene and having a hydrophobic polymer block (T) formed from a conjugated diene or isobutene will be described. In this case, it is produced by a living anionic polymerization method or a living cationic polymerization method from the viewpoint of industrial ease, molecular weight, molecular weight distribution, polymer block (S ₀ ), ease of bonding with a hydrophobic polymer block (T), and the like. The following specific examples of synthesis are shown.

In producing the block copolymer (Z ₀ ) by living anionic polymerization,
(1) In the presence of an anionic polymerization initiator in a nonpolar solvent such as cyclohexane, an aromatic vinyl compound, a conjugated diene, and an aromatic vinyl compound are sequentially polymerized under a temperature condition of 20 to 100 ° C., so that S ₀ -T— A method for obtaining an S ₀ type block copolymer (Z ₀ );
(2) A coupling agent such as phenyl benzoate after sequential polymerization of an aromatic vinyl compound and a conjugated diene in the presence of an anionic polymerization initiator in a nonpolar solvent such as cyclohexane at a temperature of 20 to 100 ° C. To obtain a S ₀ -T—S ₀ type block copolymer (Z ₀ );
(3) In the presence of an organic lithium compound as an anionic polymerization initiator in a nonpolar solvent such as cyclohexane, in the presence of a polar compound having a concentration of 0.1 to 10% by mass, at a temperature of −30 to 30 ° C., After polymerizing an aromatic vinyl compound having a concentration of 50% by mass and polymerizing a conjugated diene to the resulting living polymer, a coupling agent such as phenyl benzoate is added, and S ₀ -TS ₀ type block copolymer A method for obtaining a coalescence (Z ₀ );
(4) In the presence of an anionic polymerization initiator in a non-polar solvent such as cyclohexane, t-butylstyrene, styrene, and conjugated diene are sequentially added one or more times in the desired order under a temperature condition of 20 to 100 ° C. A method of obtaining a block copolymer (Z ₀ ) comprising three or more polymer blocks;
Etc. are adopted.

In producing the block copolymer (Z ₀ ) by living cationic polymerization,
(5) Cationic polymerization of isobutene in the presence of Lewis acid using a bifunctional halogenated initiator at -78 ° C in a mixed solvent of halogenated hydrocarbon and hydrocarbon, and then aromatic vinyl such as styrene. A method (Macromol. Chem., Macromol. Symp. 32, 119 (1990).), Etc., for polymerizing the compound to obtain an S ₀ -TS ₀ type block copolymer (Z ₀ ) is employed.

When the unsaturated hydrocarbon compound, which is a monomer that forms the hydrophobic polymer block (T), has a plurality of carbon-carbon double bonds (unsaturated bonds), the unsaturated bond usually remains after polymerization. doing. In this case, some or all of the remaining unsaturated bonds may be converted to saturated bonds by a known hydrogenation reaction. The hydrogenation rate of the carbon-carbon double bond can be calculated by a commonly used method, for example, ¹ H-NMR measurement. The hydrogenation rate of the carbon-carbon double bond is preferably 50 mol% or more, and more preferably 80 mol% or more.

The number average molecular weight of the block copolymer (Z ₀ ) is usually preferably 5,000 to 200,000 as the number average molecular weight in terms of standard polystyrene measured by a gel permeation chromatography (GPC) method, preferably 30,000. ˜150,000 is more preferable, and 50,000 to 100,000 is more preferable. When the number average molecular weight of the block copolymer (Z ₀ ) is smaller than 5000, the stability of micelles is reduced in the block copolymer solution obtained by dissolving the block copolymer (Z) obtained therefrom in an organic solvent. If it is larger than 150,000, the pore diameter of the obtained mesoporous silica is expanded and the amount of protein or drug adsorbed tends to decrease.

<Production of block copolymer (Z)>
Next, a method for producing a block copolymer (Z) by introducing a sulfonic acid group into the block copolymer (Z ₀ ) will be described. Introduction of a sulfonic acid group (sulfonation) can be performed by a known method. For example, after preparing a solution or suspension of the block copolymer (Z ₀ ), a sulfonating agent described later is added and mixed, or a gaseous sulfonating agent is directly added to the block copolymer (Z ₀ ). The method of adding is mentioned.

  As the sulfonating agent, sulfuric acid; a mixed system of sulfuric acid and an aliphatic acid anhydride; a chlorosulfonic acid; a mixed system of chlorosulfonic acid and trimethylsilyl chloride; a sulfur trioxide; a mixed system of sulfur trioxide and triethyl phosphate; Examples include aromatic organic sulfonic acid represented by 2,4,6-trimethylbenzenesulfonic acid. Examples of the organic solvent to be used include halogenated hydrocarbons such as methylene chloride, linear aliphatic hydrocarbons such as hexane, cyclic aliphatic hydrocarbons such as cyclohexane, and the like. You may select and use suitably.

[Third step]
The silica precursor aqueous solution obtained in the first step and the block copolymer solution obtained in the second step are mixed. There is no limitation on the mixing method, a method of supplying a block copolymer solution into a silica precursor aqueous solution, a method of supplying a silica precursor aqueous solution into a block copolymer solution, a silica precursor aqueous solution and a block copolymer solution, Any of the methods of simultaneously supplying the liquid into the container may be used. The mixing is preferably carried out with stirring using a known stirring device.

  The amount ratio of the aqueous silica precursor solution and the block copolymer solution is such that the mass ratio of the block copolymer (Z) to the alkoxysilane is 0.01: 1 from the viewpoint of reducing the pore size variation of the obtained mesoporous silica. The ratio is preferably 25: 1, and more preferably 0.05: 1 to 9: 1.

  The third step is preferably performed in an air atmosphere. From the viewpoint of increasing the crystallinity of the obtained mesoporous silica, the aqueous silica precursor solution used in the third step is preferably subjected to the third step within 1 hour after being prepared in the first step, and the third step within 30 minutes. More preferably, it is used. The temperature at the time of mixing has the preferable range of 0-80 degreeC, The range of 5-50 degreeC is more preferable, The range of 10-30 degreeC is further more preferable. Moreover, since highly crystalline mesoporous silica is obtained, the mixing time is preferably in the range of 1 to 300 minutes, and more preferably in the range of 30 to 90 minutes.

[Fourth step]
The organic solvent and water are removed from the mixed solution obtained in the third step to obtain a solid content. From the viewpoint of increasing the crystallinity of the obtained mesoporous silica, it is preferably provided in the fourth step within 1 hour after preparation in the third step, and more preferably provided in the fourth step within 30 minutes.

  The fourth step is preferably performed in an air atmosphere. The temperature in the fourth step is preferably in the range of 20 to 80 ° C. The time required for the fourth step is preferably in the range of 10 minutes to 6 hours, more preferably 30 minutes to 3 hours. When the solid content is held at 100 ° C. using a commercially available infrared moisture meter, it is preferable to remove the organic solvent and water until the mass reduction rate is 0.1% or less per minute.

[Fifth step]
The solid content obtained in the fourth step is baked to remove the block copolymer (Z), and mesoporous silica in which a large number of pores having a pore diameter of 2 to 50 nm are periodically formed is obtained.

  Firing is performed at 300 to 1000 ° C., preferably 400 to 700 ° C. The heating time is preferably in the range of 30 minutes to 12 hours.

  The pore diameter of mesoporous silica used for adsorption separation of proteins and the like and DDS is in the range of 2 to 50 nm, and preferably in the range of 5 to 30 nm. Here, the pore diameter refers to the pore diameter showing the maximum peak in the pore distribution curve shown in FIG. The pore distribution curve is obtained by cooling the mesoporous silica to be measured to liquid nitrogen temperature (−196 ° C.), gradually pressurizing with nitrogen gas, and plotting the adsorption amount of nitrogen gas against the equilibrium pressure of nitrogen gas by the constant volume method. It is calculated by the BJH method from the adsorption isotherm adsorption curve as shown in FIG. The BJH method is calculated by using cylindrical pores that are not connected to other pores as a model, and is a method for obtaining pore distribution from capillary condensation of nitrogen gas and multi-layer adsorption. The details are described in “Shimadzu review” (Vol. 48, No. 1, pp. 35-44, published in 1991).

  When the X-ray diffraction pattern of the mesoporous silica obtained by the production method of the present invention is measured, it is preferable that the X-ray diffraction pattern has one or more peaks at a diffraction angle corresponding to a d value of 1 nm or more. The X-ray diffraction peak means that a periodic structure having a d value corresponding to the peak angle is present in the sample. Therefore, having one or more peaks at a diffraction angle corresponding to a d value of 1 nm or more means that the pores are regularly arranged at intervals of 1 nm or more.

  As described above, in the block copolymer (Z) comprising the hydrophilic polymer block (S) having a sulfonic acid group and the hydrophobic polymer block (T) in the present invention, the hydrophilic polymer Since the difference in hydrophilicity and hydrophobicity between the block (S) and the hydrophobic polymer block (T) is extremely large, stable micelles can be formed. Moreover, since the hydrophilic polymer block (S) is composed of structural units derived from bulky aromatic vinyl compounds, it is considered that the hydrophilic polymer block (S) functions as pores that connect the pores after firing. As a result, mesoporous silica having a large pore diameter in which pores are connected can be produced at a low temperature in a short time, which is an industrially advantageous production process.

  Hereinafter, the present invention will be described in more detail. In addition, this invention is not limited to the Example demonstrated here. First, the measurement method and conditions used are shown.

1. Measurement of the number average molecular weight of the block copolymer (Z ₀ ) by GPC;
GPC system: HLC-8220GPC manufactured by Tosoh Corporation
Column: TSKgel Super Multipore HZ-M
TSK guard Column Super MP-M
TSK gel G3000H
RI detector: HLC-8220GPC
Column oven temperature: 40 ° C
Eluent: Tetrahydrofuran Standard sample: Converted using standard polystyrene calibration curve

2. Measurement of hydrogenation rate of block copolymer (Z ₀ ) and sulfonation rate of block copolymer (Z) by ¹ H-NMR;
NMR system: JEOL JNM-ECX400
Solvent: Deuterated chloroform Standard peak: Tetramethylsilane

3. Measurement of storage modulus A 20% by weight toluene / isopropyl alcohol (mass ratio 5/5) solution of the block copolymer (Z) was prepared, and a release-treated PET film [Mitsubishi Resin Co., Ltd., MRV (trade name) ]] Was coated at a thickness of about 350 μm, dried with a hot air dryer at 100 ° C. for 4 minutes, and then peeled off from the release-treated PET film at 25 ° C. to obtain a film with a thickness of 30 μm. Using the wide-range dynamic viscoelasticity measuring device ("DVE-V4FT Rheospectr" manufactured by Rheology Co., Ltd.), the resulting film was heated in a tensile mode (frequency: 11 Hz) at a heating rate of 3 ° C / min,- The temperature was raised from 80 ° C. to 250 ° C., and the storage elastic modulus (E ′), loss elastic modulus (E ″), and loss tangent (tan δ) were measured. Based on the fact that there was no change in the storage elastic modulus at 80 to 100 ° C. derived from the crystallized olefin polymer, the amorphous nature of the hydrophobic polymer block (T) was judged. As a result, the hydrophobic polymer block (T) was amorphous for all the block copolymers (Z) obtained in the following Examples and Comparative Examples.

4). Measurement of pore size and specific surface area of mesoporous silica BEL specific surface area by multipoint method using liquid nitrogen and using an automatic specific surface area / pore distribution measuring device, trade name “BELSORP-miniII”, manufactured by Nippon Bell Co., Ltd. And the value was derived in the range where the parameter C becomes positive. For the pore distribution, the BJH method described above was adopted, and the peak top was the pore diameter. Pretreatment was performed at 100 ° C. for 24 hours.

[Synthesis Example 1: Synthesis of block copolymer (Z ₀ -1) comprising poly α-methylstyrene and hydrogenated polybutadiene]
After sufficiently substituting the pressure vessel equipped with a stirrer with nitrogen, 172 g, 258.1 g, 28.8 g and 5.9 g of α-methylstyrene, cyclohexane, n-hexane and tetrahydrofuran, which were sufficiently dehydrated, were added, respectively. Subsequently, 17.5 ml of sec-butyllithium (1.3 M, cyclohexane solution) was added, and polymerization was performed at −10 ° C. for 5 hours. When the number average molecular weight of the poly α-methylstyrene after polymerization for 5 hours was measured by GPC, it was 6,400 in terms of polystyrene. Next, 27 g of 1,3-butadiene was added, and after stirring for 30 minutes, 1,703 g of cyclohexane was added. The number average molecular weight of the poly 1,3-butadiene block (b1) was 3640. Next, 303 g of 1,3-butadiene was added, and polymerization was carried out for 2 hours while raising the temperature to 60 ° C. Furthermore, 27.0 ml of α, α′-dichloro-p-xylene (0.3 M, toluene solution) was added to the polymerization solution in the pressure vessel, and the mixture was stirred at 60 ° C. for 1 hour to conduct a coupling reaction. An α-methylstyrene) -polybutadiene-poly (α-methylstyrene) type copolymer (hereinafter abbreviated as mSEBmS) was synthesized. The number average molecular weight of the obtained mSEBmS was 74000, the 1,2-bond amount determined from ¹ H-NMR measurement was 43.9%, and the content of α-methylstyrene unit was 28% by mass. Further, it was found by composition analysis by ¹ H-NMR spectrum measurement that α-methylstyrene was not substantially copolymerized in the polybutadiene block.

Prepare a synthesized cyclohexane solution of mSEBmS, charge it in a pressure-resistant vessel with sufficient nitrogen substitution, and then hydrogenate it at 80 ° C. for 5 hours in a hydrogen atmosphere using a Ni / Al Ziegler hydrogenation catalyst. The reaction was carried out to obtain a poly α-methylstyrene-b-hydrogenated polybutadiene-b-polyα-methylstyrene type triblock copolymer (hereinafter referred to as a block copolymer (Z ₀ -1)). The resulting block copolymer hydrogenation rate of _(Z 0 -1) was calculated by ¹ H-NMR spectrum measurement, it was 99.6%.

[Synthesis Example 2: Synthesis of block copolymer (Z-1)]
100 g of the block copolymer (Z ₀ -1) obtained in Synthesis Example 1 was vacuum-dried for 1 hour in a glass reaction vessel equipped with a stirrer, and then purged with nitrogen. Then, 1000 ml of methylene chloride was added, and 35 ° C. And stirred for 2 hours to dissolve. After dissolution, a sulfating reagent obtained by reacting 21.0 ml of acetic anhydride and 9.34 ml of sulfuric acid at 0 ° C. in 41.8 ml of methylene chloride was gradually added dropwise over 20 minutes. After stirring at 35 ° C. for 0.5 hour, the polymer solution was poured into 2 L of distilled water while stirring to coagulate and precipitate the polymer. The precipitated solid was washed with distilled water at 90 ° C. for 30 minutes and then filtered. This washing and filtration operation was repeated until there was no change in the pH of the washing water, and the polymer collected by filtration at the end was vacuum dried to obtain a sulfonated product (hereinafter referred to as block copolymer (Z-1)). . The sulfonation rate of the benzene ring of the α-methylstyrene unit of the obtained block copolymer (Z-1) was 27 mol% from ¹ H-NMR analysis, and the ion exchange capacity determined by acid value titration was 0.8 meq / g. Met.

[Synthesis Example 3: Synthesis of block copolymer (Z-2)]
The reaction was performed in the same manner as in Synthesis Example 2 except that the reaction temperature of Synthesis Example 2 was changed to 25 ° C. and the reaction time was changed to 3 hours. The sulfonation rate of the benzene ring of the α-methylstyrene unit of the obtained sulfonated product (hereinafter referred to as block copolymer (Z-2)) was 36 mol% from ¹ H-NMR analysis, and the ion obtained by acid value titration. The exchange capacity was 0.88 meq / g.

[Synthesis Example 4: Synthesis of block copolymer (Z-3)]
The same procedure as in Synthesis Example 3 was performed except that the reaction time in Synthesis Example 3 was changed to 7 hours. The sulfonation rate of the benzene ring of the α-methylstyrene unit of the obtained sulfonated product (hereinafter referred to as block copolymer (Z-3)) was 50 mol% from ¹ H-NMR analysis, and the ion determined by acid value titration. The exchange capacity was 1.06 meq / g.

[Synthesis Example 5: Synthesis of block copolymer of styrene polymer block and ethylene oxide polymer block (hereinafter referred to as block copolymer (Q)]]
20 g of monomethoxypolyethylene oxide (PEG 5000 manufactured by Acros) was dissolved in 60 ml of THF. To this, 40 ml of pyridine was added to obtain a uniform solution. The solution was cooled in an ice bath, 13 mmol of 2-bromoisobutyryl bromide (Acros) was added dropwise over 30 minutes, and the mixture was further stirred at 30 ° C. for 12 hours. After cooling to room temperature, 200 ml of cooled dimethyl ether was added to the solution to obtain white PEO-Br as a precipitate. PEO-Br was washed with cooled dimethyl ether and dried in vacuo. Next, PEO-Br 3 g, CuBr 0.08 g, N, N, N ′, N′-pentamethyldiethylenetriamine (manufactured by Acros) 0.10 g, and styrene (manufactured by Wako Pure Chemical Industries) 15 g are put into an ampule tube and removed. After the oxygen treatment, a polymerization reaction was carried out at 110 ° C. for 3 hours. The obtained gel-like product was dissolved in 50 ml of THF and passed through an alumina column to remove the Cu complex. The block copolymer (Q) was obtained by adding 200 ml of petroleum ether to this and performing a reprecipitation process. The number average molecular weight of the obtained block copolymer (Q) was 36100.

<Synthesis of mesoporous silica>

  0.15 g of 0.1M hydrochloric acid aqueous solution is added to 0.5 g of tetraethoxysilane (manufactured by Aldrich), and the silica precursor aqueous solution is prepared by stirring with a magnetic stirrer at 25 ° C. for 5 minutes in an air atmosphere. Prepared. Next, 2.5 ml of THF was added to 0.0556 g of the block copolymer (Z-3) synthesized in Synthesis Example 4, and the block copolymer was stirred by using a magnetic stirrer at 25 ° C. for 1 hour in an air atmosphere. A polymer solution was prepared. Next, the previously prepared silica precursor aqueous solution was added and stirred for 1 hour. The obtained liquid mixture was dried at 25 ° C. for 1 hour in an air atmosphere to obtain a solid content, transferred to an electric furnace (KBF442N1 manufactured by Koyo Thermo Systems), and heated at a rate of 1 ° C./min in the air atmosphere. The temperature was raised to 600 ° C. and maintained for 4 hours, and then the power was turned off and cooled to room temperature to obtain mesoporous silica.

  Except having changed the addition amount of the block copolymer (Z-3) of Example 1 into 0.125g, it carried out similarly to Example 1 and obtained mesoporous silica.

  Except having changed the addition amount of the block copolymer (Z-3) of Example 1 into 0.2143g, it carried out similarly to Example 1 and obtained mesoporous silica.

  Except having changed the addition amount of the block copolymer (Z-3) of Example 1 into 0.3333 g, it carried out similarly to Example 1 and obtained mesoporous silica.

  Except having changed the addition amount of the block copolymer (Z-3) of Example 1 into 0.5 g, it carried out similarly to Example 1 and obtained mesoporous silica.

  Except having changed the addition amount of the block copolymer (Z-3) of Example 1 into 0.75g, it carried out similarly to Example 1 and obtained mesoporous silica.

  A mesoporous silica was obtained in the same manner as in Example 1 except that 0.125 g of the block copolymer (Z-1) synthesized in Synthesis Example 2 was added.

  Mesoporous silica was obtained in the same manner as in Example 1 except that 0.2143 g of the block copolymer (Z-1) synthesized in Synthesis Example 2 was added.

  Mesoporous silica was obtained in the same manner as in Example 1 except that 0.3333 g of the block copolymer (Z-1) synthesized in Synthesis Example 2 was added.

  Mesoporous silica was obtained in the same manner as in Example 1 except that 0.125 g of the block copolymer (Z-2) synthesized in Synthesis Example 3 was added.

  Mesoporous silica was obtained in the same manner as in Example 1 except that 0.2143 g of the block copolymer (Z-2) synthesized in Synthesis Example 3 was added.

  Mesoporous silica was obtained in the same manner as in Example 1 except that 0.3333 g of the block copolymer (Z-2) synthesized in Synthesis Example 3 was added.

Comparative Example 1

  30 g of water was added to 4 g of a nonionic triblock copolymer having a propylene oxide polymer block between two ethylene oxide polymer blocks (BASF P123 brand; molecular weight 5900), and the temperature was increased to 25 ° C. in an air atmosphere. Then, a block copolymer solution was prepared by stirring with a magnetic stirrer for 1 hour, then 120 g of 2M hydrochloric acid was added, the temperature was raised to 35 ° C., and the mixture was stirred for 5 minutes. Next, 8.5 g of tetraethoxysilane was added and stirred at 35 ° C. for 20 hours using a magnetic stirrer. The obtained mixed liquid was transferred to a pressure-resistant container coated with Teflon (registered trademark) and heated at 80 ° C. for 12 hours to obtain a solid as a precipitate. The solid content was recovered by filtration, rinsed with 50 ml of water, and then dried at 25 ° C. for 12 hours in an air atmosphere. Transfer this to an electric furnace (KBF442N1 manufactured by Koyo Thermo Systems Co., Ltd.), raise the temperature to 600 ° C. at a temperature increase rate of 1 ° C./min in an air atmosphere, hold it for 4 hours, then turn off the power and cool to room temperature. To obtain mesoporous silica.

Comparative Example 2

  2M hydrochloric acid 60 g, nonionic triblock copolymer 1.01 g (BASF F127 brand; molecular weight 12600) having a propylene oxide polymer block between two ethylene oxide polymer blocks, KCl 1.42 g, 1, 3, 2.16 g of 5-trimethylbenzene was mixed and stirred using a magnetic stirrer at 15 ° C. for 24 hours in an air atmosphere. Then, 3.96 g of tetraethoxysilane was added and stirred for 24 hours. The obtained mixed liquid was transferred to a pressure-resistant container coated with Teflon (registered trademark) and heated at 100 ° C. for 72 hours to obtain a solid as a precipitate. The solid content was collected by filtration and further rinsed with 50 ml of water. After drying this solid content at 25 ° C. for 12 hours in an air atmosphere, the solid content is transferred to an electric furnace (KBF442N1 manufactured by Koyo Thermo Systems Co., Ltd.) to 600 ° C. at a temperature increase rate of 1 ° C./min in the air atmosphere. The temperature was raised and held for 4 hours, and then the power supply was turned off and cooled to room temperature to obtain mesoporous silica.

Comparative Example 3

  A silica precursor aqueous solution was prepared by adding 0.3 g of 0.1M hydrochloric acid to 1 g of tetraethoxysilane (manufactured by Aldrich) and stirring the mixture using a magnetic stirrer at 25 ° C. for 5 minutes in an air atmosphere. Next, 2.5 ml of THF was added to 0.1 g of the block copolymer (Q) synthesized in Synthesis Example 5, and the block copolymer was stirred by using a magnetic stirrer at 25 ° C. for 1 hour in an air atmosphere. A solution was prepared. After the silica precursor aqueous solution was added to the block copolymer solution, the mixture was stirred with a magnetic stirrer at 25 ° C. for 1 hour in an air atmosphere. The obtained liquid mixture was dried at 25 ° C. for 1 hour in an air atmosphere to obtain a solid content, and then transferred to an electric furnace (KBF442N1 manufactured by Koyo Thermo Systems). The temperature was raised to 600 ° C. at a rate of temperature rise and held for 4 hours, and then the power was turned off and cooled to room temperature to obtain mesoporous silica.

  The X-ray diffraction pattern by GI-SAXS after firing of the mesoporous silica obtained in Examples 1, 2, and 4 is shown in FIG. Moreover, the scanning electron micrograph of the mesoporous silica obtained in Examples 1-6 is shown in FIG. 2, and the transmission electron micrograph of the mesoporous silica obtained in Examples 2 and 5 is shown in FIG. 1, 2 and 3, it was found that the mesoporous silica obtained in the example has a spherical pore shape.

  The nitrogen adsorption isotherm of the mesoporous silica obtained in Examples 1 to 6 is shown in FIG. It is believed that mesoporous silica was obtained from the hysteresis of this nitrogen adsorption isotherm. FIG. 5 shows a pore distribution curve calculated using the BJH method from the nitrogen adsorption isotherm of FIG.

  Table 1 shows data on the pore diameter, specific surface area, and pore volume of the mesoporous silica obtained in Examples and Comparative Examples. The specific surface area was calculated from the adsorption isotherm curve of FIG. 4 using the BET method. The pore volume was calculated from the adsorption curve of the adsorption isotherm in FIG. 4 using the t method. The pore diameter of Comparative Example 1 is 4.7 nm, which is not a pore diameter suitable for adsorption of a huge molecular size such as protein or drug. In Comparative Example 2, by adding an organic swelling agent and applying a hydrothermal treatment, the pore diameter is expanded to 26 nm, the specific surface area and the pore volume are both large, and mesoporous silica suitable for macromolecule adsorption is obtained. On the other hand, in Comparative Example 3, spherical pores near 31 nm were observed from XRD diffraction and scanning electron micrographs, but the amount of nitrogen gas adsorbed was small and the specific surface area was also low. For this reason, adsorption of huge molecules such as proteins and drugs cannot be expected. The mesoporous silica other than Comparative Example 3 is white, whereas the mesoporous silica of Comparative Example 3 is gray, suggesting the possibility that residues derived from the block copolymer are contained in isolated pores. This is presumed to be due to the low surface area. In this example, a pore diameter of 16.9 to 27.1 nm was obtained without adding an organic swelling agent or hydrothermal treatment, and mesoporous silica having a large specific surface area and pore volume was obtained.

Claims (3)

A first step of preparing an aqueous silica precursor solution by dissolving an alkoxysilane in an acidic aqueous solution;
Hydrophobic polymer comprising a hydrophilic polymer block (S) having a structural unit derived from an aromatic vinyl compound and having a sulfonic acid group, and an amorphous polymer containing a structural unit derived from an unsaturated hydrocarbon compound A second step of preparing a block copolymer solution by dissolving the block copolymer (Z) having the combined block (T) as a constituent component in an organic solvent;
A third step of mixing the silica precursor aqueous solution and the block copolymer solution;
A fourth step of removing the organic solvent and water from the liquid mixture obtained in the third step to obtain a solid content; and a fifth step of firing the solid content obtained in the fourth step. A process for producing mesoporous silica, characterized by   The manufacturing method of Claim 1 whose equivalent number of the sulfonic acid group per unit mass of a block copolymer (Z) is 0.10 meq / g or more and 5.00 meq / g or less. The manufacturing method of Claim 1 or 2 whose mass ratio of the block copolymer (Z) and alkoxysilane in the liquid mixture obtained at the 3rd process is 0.01: 1-25: 1.