WO2009093561A1

WO2009093561A1 - Process for production of inorganic nanoparticle using colloid as precursor and/or intermediate

Info

Publication number: WO2009093561A1
Application number: PCT/JP2009/050728
Authority: WO
Inventors: Tomohiro Iwasaki
Original assignee: Osaka Prefecture University Public Corporation
Priority date: 2008-01-22
Filing date: 2009-01-20
Publication date: 2009-07-30
Also published as: JPWO2009093561A1

Abstract

The object is to allow the reaction to proceed only with a mechanical energy (a mechanochemical effect) without using any organic solvent system or any additive such as an oxidizing agent, a reducing agent and a surfactant and without the need of heating from an aqueous system, and to improve the crystallinity without growing particles. Specifically disclosed is a process for producing an inorganic nanoparticle by using a colloid as a precursor and/or an intermediate, which comprises the steps of: producing a colloidal material by using an aqueous solution of an inorganic compound; mixing the colloidal material, as a precursor and/or an intermediate, by ball-mill-type mechanical stirring for a predetermined period at a low temperature in an inert atmosphere until any unreacted colloidal material does not appear; centrifuging the mixture to obtain particles; and washing and drying the particles.

Description

Method for producing inorganic nanoparticles using colloid as precursor or / and intermediate

The present invention relates to a production method for obtaining inorganic nanoparticles such as magnetite particles that can be produced from an aqueous system.

Inorganic nanoparticles such as metals and ceramics are widely used as raw materials in various industries. Among them, magnetite (magnetite, triiron tetroxide) nanoparticles, one of the metal oxides, are ferromagnetic and have excellent electrical conductivity. Therefore, it is widely used as an electronic material. In particular, recently, there is an increasing need for magnetite nanoparticles of 10 nanometers or less because of high integration of electronic devices and attempts in medical fields such as drug delivery systems. There are many methods for synthesizing magnetite nanoparticles, but the coprecipitation method (colloid method), in which divalent and trivalent iron ions are reacted in an aqueous solution, compares the operations of washing the product and separating it from the liquid phase. It is often used because of its simplicity (see Non-Patent Document 1).

The coprecipitation method performs the reaction at room temperature, so that the crystallinity of the product is lowered. The magnetic properties of magnetite, which are extremely important for practical use, depend strongly on their crystallinity and homogeneity, so the product obtained by the coprecipitation method is heated in an inert atmosphere after the reaction ( Annealing and annealing). Although the crystallinity and homogeneity are improved by performing the heat treatment, particle growth also occurs at the same time. Therefore, even if it is 10 nanometers or less before the heat treatment, it becomes 20 nanometers or more after the heat treatment. The hydrothermal method corresponds to a combination of the coprecipitation method and the subsequent heat treatment, but the same phenomenon occurs and particle growth is unavoidable.

Magnetite nanoparticles have been used in the medical field as a contrast agent for magnetic resonance imaging (MRI) (superparamagnetic iron oxide, Super Paragonic Iron Oxide: SPIO), but recently formed a complex with a drug. Research is also underway to target this to the affected area (tumor) (drug delivery system, DDS). At this time, a complex of magnetite and drug is injected into the blood, and this is delivered to the affected area using a magnet. However, it is necessary that the magnetite nanoparticles used are superparamagnetic materials of 10 nanometers or less. Become. That is, the superparamagnetic material exhibits ferromagnetism only when an external magnetic field is generated by bringing the magnet close to it, and when the external magnetic field is removed, there is no residual magnetization and the coercive force becomes zero. . As a result, a large reaction area is obtained, and further, the effect of treatment is expected to be improved because it does not settle in blood. On the other hand, since magnetite nanoparticles larger than 10 nanometers are not superparamagnetic materials, residual magnetization occurs even when the external magnetic field is removed, and magnetization cohesion is likely to occur due to the coercive force.

In the conventional method for producing superparamagnetic magnetite nanoparticles, an organic solvent is used or a surfactant is used in an aqueous system, which is inappropriate for application to the human body. Thus, an example of synthesizing superparamagnetic magnetite nanoparticles having a high crystallinity of 10 nanometers or less without using an organic solvent or a surfactant in an aqueous system has not yet been reported.
As described above, in the conventional method for preparing magnetite nanoparticles, a surfactant is added to suppress particle growth due to aggregation in the synthesis process, but in the present invention, any additive such as a surfactant is used. First, superparamagnetic magnetite nanoparticles having ferromagnetism of 10 nanometers or less are prepared.

Furthermore, there is Patent Document 1 as a method using an organic solvent. However, organic solvent systems are difficult to handle environmentally.

As a method for synthesizing magnetite fine particles from an aqueous solution having a temperature of room temperature or lower, there are Patent Document 2 and Patent Document 3, but there are the following problems.
(A) In any method, synthesis takes a long time (several days).
(B) Annealing is required after synthesis.
(C) An additive such as an oxidizing agent is used.
(D) The magnetic properties of the product are not good.
(E) The particle size is very large.
Japanese Patent No. 39898868 JP 09-169525 A JP 2006-219353 A JP 2007-023027 A " "S. Meerod, G. Tumcharern, U. Wichai, M. Rutnakonpituk, Magnetotide nanopolys stabile with a highly polymerized solid polymer of e-ylene.

The problem to be solved is that, in the conventional coprecipitation method, the reaction is performed at room temperature, so that the crystallinity of the product is low, and even if it is 10 nanometers or less before the heat treatment, 20 nanometers after the heat treatment. It is the point which becomes more than a meter. In addition, in the conventional method for producing superparamagnetic magnetite nanoparticles, an organic solvent is used or a surfactant is used in an aqueous system, which is inappropriate for application to the human body.

The present invention does not use additives such as organic solvent systems, oxidants, reducing agents, surfactants, etc., and mechanical energy ( An object of the present invention is to provide a method for producing inorganic nanoparticles, which advances the reaction only by mechanochemical effect) and improves the crystallinity without causing particle growth at the same time.

The solution of claim 1 of the present invention is that a colloidal state is produced using an aqueous solution of an inorganic compound, and the colloidal state is used as a precursor or / and an intermediate in an inert atmosphere and at a low temperature for a predetermined time. In the meantime, ball mill mechanical stirring and mixing is performed to confirm that there is no unreacted colloid, the particles are centrifuged, washed, and then dried, and the colloid is characterized as a precursor or / and an intermediate. It is a method for producing inorganic nanoparticles.

The solution of claim 2 of the present invention is to produce an inorganic compound in a colloidal form from an aqueous solution, using the colloidal state as a precursor or / and an intermediate, and a rotational speed of 35 rpm to 140 rpm in an inert atmosphere and at a low temperature. It is characterized in that it is mixed by ball mill mechanical stirring and mixing for 12 hours on the low rotation side to 6 hours on the high rotation side, and confirmed that there is no unreacted colloid, and the particles are centrifuged, washed and dried. Yes.

According to a third aspect of the present invention, sodium hydroxide corresponding to the stoichiometric ratio is dropped into an aqueous solution of an inorganic compound to adjust the pH to near neutrality, and the rotation is performed 140 times per minute in an inert atmosphere. It is characterized by performing ball milling at room temperature for 2 hours at room temperature.

Further, the solution of claim 4 uses a mixture of ferrous sulfate heptahydrate and ferric chloride hexahydrate as an inorganic compound, and adds sodium hydroxide to form a colloidal form at 5 ° C. Although it takes several days in the above, the reaction due to heat proceeds slowly in a standing state. To suppress this, magnetite nanoparticles are produced by the method described in the previous section at a low temperature of 5 ° C. or less. Yes.

Furthermore, the solution of claim 5 is characterized in that when sodium hydroxide is added, the pH is maintained at 12 or higher, and the inorganic nanoparticles having the colloid as a precursor or / and an intermediate as described above are used. This method is characterized in that it is a method for producing magnetite nanoparticles.

The present invention can be carried out in an environmentally friendly aqueous system without using an additive such as a surfactant, an oxidant, and a reducing agent in an organic solvent, and is not mechanically heat as energy for advancing the reaction. In order to use energy (mechanochemical effect, mechanochemical reaction) and advance the reaction only by the mechanochemical effect, it can be carried out at a low temperature, does not add heat, and acts on mechanical energy. Therefore, it is possible to realize high crystallization while suppressing particle growth and to control the progress of the reaction by mechanical energy, that is, milling conditions.

Furthermore, the present invention uses nanoparticle colloidal particle suspension as a starting solution to produce nanoparticles having colloidal precursors and / or intermediates such as iron oxides such as magnetite and hematite, and ferrites such as zinc and manganese. In addition, it is applicable to the complexization.

The sample synthesized without adding a surfactant by the conventional method (hydrothermal method) has an average particle diameter of 39 nm and is very large, and the saturation magnetization is 79 emu / g and exhibits ferromagnetism, but the coercive force is 73 Oe and is supernormal. It is not magnetic. Table 1 shows a comparison between the conventional hydrothermal method and the method according to the present invention.

Although the rotation speed of the ball mill container has an influence on the synthesis time, it has been confirmed that it has almost no influence on the particle size and magnetic properties of the product, and is 120 to 160 rpm (85% to 115% of the critical rotation speed). The synthesis is preferably within 12 hours.
The size, filling amount, and material of the ball change the mechanical energy acting on the sample suspension per unit time, but it only affects the length of the synthesis time as well as the rotational speed of the ball mill container. A preferable range of the dynamic energy is 2 J / s to 30 J / s (calculated from a discrete element simulation of medium ball behavior).

It is a process flow figure in an embodiment of the present invention. It is a front view of the ball mill type agitator used for the embodiment of the present invention. It is an X-ray-diffraction pattern of the product in Example 1 of this invention, (a) Before milling process, (b) Milling process 1 hour, (c) Milling process 3 hours, (d) Milling process 6 hours, (e ) 9 hours of milling process. It is an electron micrograph of the product of the milling process for 9 hours in Example 1 of this invention. In Example 2 of this invention, it is a figure which shows the relationship between the magnitude | size of the obtained particle size, and frequency (%). It is an X-ray-diffraction pattern of the product in the comparative example 1, and is a pattern of a starting solution (a) and cooling stationary 24 hours (b). 2 is an electron micrograph of a product of a starting solution (a) and a cooled standing for 24 hours (b) in Comparative Example 1. FIG. It is a X-ray-diffraction pattern of the product in the comparative example 2 of this invention, The product of the milling process of Example 1 after 9 hours (a), and the product of the comparative example 2 after 9 hours of heating standing (b) It is an X-ray diffraction pattern. 4 is an electron micrograph of a product after 9 hours of heating and standing in Comparative Example 2.

As shown in the process flow diagram of the first embodiment of the present invention in FIG. 1, ferrous sulfate heptahydrate (FeSO4 7H2 O) 1.5 mmol (0.417 grams) and ferric chloride hexahydrate 3.0 mmol (0.812 g) of (FeCl3 · 6H2 O) was dissolved in 60 mL of deoxygenated ion exchange water while cooling to 5 ° C. or less (first step). Next, while stirring the aqueous solution vigorously with a magnetic stirrer, a 1N sodium hydroxide solution cooled to 5 ° C. or less was added to the aqueous solution at a rate of 3 ml / min (the concentration and dropping rate of the sodium hydroxide solution were preliminary experiments). Was added dropwise (pH> 12 at this time) to obtain a dark brown colloidal suspension as a starting solution (second step). At this time, a sodium hydroxide solution was dropped in an argon atmosphere in order to prevent oxidation of divalent iron ions. At this time, the following reaction occurs. A small amount of magnetite (Fe 3 O 4 生成) formation reaction occurs immediately when the pH is raised even under cooling, but the further reaction can be suppressed by cooling, and the formation reaction of magnetite proceeds only with mechanical energy. .

^{^{Fe 2+ + 2OH - → Fe (}} OH) 2 (1)
Fe ³⁺ + 3OH ⁻ → Fe (OH) 3 (2)
Fe (OH) 3 → α-FeOOH + H2O (3)
Fe (OH) 2 + 2α-FeOOH → Fe3 O4 + 2H2 O (4)

The suspension thus prepared was transferred to a stainless steel rolling ball mill (inner diameter: 90 mm, capacity: 500 ml) cooled to 5 ° C. or less. After replacing the gas phase with argon, the ball mill container was Sealed (third step). A stainless steel ball having a diameter of 3.2 millimeters (1/8 inch) was used as the medium ball, and the filling amount was 40% of the container (including the space between the balls). The ball mill container was cooled from the outside and rotated at a rotation speed of 140 times per minute with the inside kept at 5 ° C. or less (fourth step). After a predetermined milling time had elapsed (fifth step), the suspension and the medium balls were taken out from the ball mill container and separated using a wire mesh (sixth step). Next, the operation of centrifuging particles from the suspension and washing with ion-exchanged water was repeated three times (seventh step) and dried overnight under reduced pressure (eighth step).

The ball mill type agitator used in the present invention is shown in FIG. 2 as a front view. A ball mill container turntable 2 is laid in the insulated water tank 1, and the ball mill container 3 is placed thereon so as to be supported by rotation, and is rotated by a motor 4. The ball mill container contains a suspension and a suitably sized stainless steel ball.

Various properties of the particles thus obtained were evaluated by the following methods.
As an evaluation method,
(B) Identification: The X-ray diffraction pattern of the sample was compared with a known magnetite pattern by a powder X-ray diffractometer (RINT-1500 manufactured by Rigaku).
(B) Particle size: Measured with a scanning electron microscope (JSM-6700FW manufactured by JEOL). (C) Magnetism: Measured (confirmed to be ferromagnetic) with a superconducting quantum interference device magnetometer (MPMS manufactured by Quantum Design).

Example 1
FIG. 3 shows the pre-milling process (a), milling process 1 hour (b), milling process 3 hours (c), milling process 6 hours (d), and milling process 9 hours (e) in Example 1 of the present invention. It is an X-ray diffraction pattern of the product obtained by changing.
As can be seen from the X-ray diffraction pattern of FIG. 3, the presence of unreacted goethite (α-FeOOH) (appears at 2θ = 21.2 degrees on the horizontal axis) was confirmed in the treatment for 3 hours or less. It was found that a substantially uniform magnetite phase was formed by the treatment for 6 hours or more. From the electron microscope observation, the size of the magnetite nanoparticles obtained by the milling treatment for 9 hours was about 10 nanometers. When the saturation magnetization value was measured as a magnetic characteristic, it was 70.5 emu / g, and although the value was slightly small because the particles were very fine, it was sufficient for practical use. FIG. 4 is an image of the nanoparticle diameter of the product after 9 hours of milling using an electron microscope.

(Example 2)
Experiments were carried out while changing the rotation speed of the ball mill container, and it was found that the magnetite formation reaction was completed in a process of 12 hours at 35 rpm, 9 hours at 70 rpm, and 6 hours at 140 rpm. Table 2 shows the physical properties of the obtained sample. FIG. 5 is a graph showing the relationship between the obtained particle size and frequency (%). According to this, the obtained particle diameter is predominantly around 10 nanometers, and all the particle diameters are 12 nanometers or less.

(Example 3)
The amount of 1N sodium hydroxide aqueous solution dropped into the aqueous solution of ferrous sulfate and ferric chloride was adjusted to 12 ml corresponding to the stoichiometric ratio, and the pH of the aqueous solution was adjusted to near neutral (approximately 7.5). When the resulting suspension was ball milled at room temperature for 2 hours at a rotational speed of 140 revolutions per minute, about 10 nanometer magnetite particles having relatively high crystallinity were obtained. Since the saturation magnetization value of this product was 72 emu / g and the coercive force was 5 Oe, it was confirmed that ferromagnetic superparamagnetic magnetite nanoparticles can be obtained at room temperature in a short time.

Example 4
Dissolve 4.5 mmol of ferrous sulfate alone in 60 ml of water, add 30 ml of 1N sodium hydroxide aqueous solution at a rate of 3 ml / min, and ball suspension for 6 hours at a rotational speed of 140 rpm. As a result, about 20 nanometer magnetite nanoparticles having relatively high crystallinity were obtained.

(Example 5)
4.5 mmol of ferrous sulfate and 4.5 mmol of sodium thiosulfate as a reducing agent are dissolved in 60 ml of water, 30 ml of 1N sodium hydroxide aqueous solution is added thereto at a rate of 3 ml per minute, and the resulting suspension is added at 140 rpm. When ball milling was performed for 6 hours at a rotational speed of 10 to 20 nanometers of magnetite nanoparticles with relatively high crystallinity were obtained.

(Comparative Example 1)
The starting solution prepared at 5 ° C. was sealed in a stainless steel sealed container (the gas phase was replaced with argon), and allowed to stand at 5 ° C. for 24 hours. FIG. 6 is an X-ray diffraction pattern of the starting solution (a) and 24 hours after cooling standing (b) in Comparative Example 1, and FIG. 7 shows the starting solution before milling (A) and 24 hours after cooling standing ( It is an electron micrograph of B).
As can be seen from these, the obtained product was observed with an electron microscope, and its X-ray diffraction pattern was measured. As a result, there was no change from those of the starting solution (many needle-like goethite particles were present). Thus, it was found that the reaction hardly progressed at 5 ° C.

(Comparative Example 2)
The starting solution prepared at 5 ° C. was sealed in a stainless steel sealed container (the gas phase was replaced with argon), and was left to stand in an oven maintained at 120 ° C. for 9 hours (hydrothermal synthesis). FIG. 8 is an X-ray diffraction pattern (a) of the product after 9 hours (a) of the milling treatment in Example 1 and an X-ray diffraction pattern of the product after 9 hours of heating and standing in Comparative Example 2 (b). FIG. 9 is an electron micrograph of the product after 9 hours of heating and standing.
As can be seen from these figures, the X-ray diffraction pattern of the obtained product was measured. As a result, the crystallinity was higher than that of the product obtained by the milling treatment of Example 1 for 9 hours. From observation, the particle diameter was 20 nanometers or more, and particle growth was confirmed.

If the molar ratio of the divalent and trivalent iron ions as the raw material is 1: 2, these may be replaced with other compounds (for example, using FeCl2Ｆｅ instead of FeSO4). Further, the alkaline solution for raising the pH of the aqueous solution may be other than the sodium hydroxide solution.

媒体 A media mill equipped with a temperature control (cooling) device can be used even if the motion mechanism of the media is different. The cooling temperature may be other temperature as long as the reaction does not proceed (however, it should be higher than the temperature at which the solution freezes).

Equipment and operating conditions such as ball mill container and medium ball size and material, container rotation speed, ball filling amount, and milling time are not particularly limited as long as the mechanical energy applied to the sample exceeds a certain threshold. None (these are factors controlling homogeneity and properties).

The milling processing time in the present invention is related to the rotation speed and speed of the ball mill, but these are not so much influence, but rather the influence of the cooling temperature etc. seems to be stronger.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Warm water tank 2 Ball mill container turntable 3 Ball mill container 4 Motor

Claims

An inorganic compound is formed in a colloidal form from an aqueous solution, and the colloidal state is used as a precursor or / and an intermediate, in an inert atmosphere and at a low temperature, for a predetermined period of time by a ball mill mechanical stirring and mixing, and unreacted. A method for producing inorganic nanoparticles using a colloid as a precursor or / and an intermediate, which comprises confirming the absence of a colloid, centrifuging the particles, washing, and drying.
An inorganic compound is formed in a colloidal form from an aqueous solution, and the colloidal state is used as a precursor or / and an intermediate, in an inert atmosphere and at a low temperature, at a rotation speed of 35 rpm to 140 rpm on the low rotation side for 12 hours to the high rotation side 6. The colloid precursor according to claim 1, wherein the colloid is mechanically stirred and mixed for 6 hours to confirm that there is no unreacted colloid, the particles are centrifuged, washed, and then dried. Or / and a method for producing inorganic nanoparticles as an intermediate.
Sodium hydroxide corresponding to the stoichiometric ratio is dropped into an aqueous solution of an inorganic compound to adjust the pH to near neutrality, and ball milling is performed at room temperature for 2 hours at 140 rotations per minute in an inert atmosphere. A method for producing inorganic nanoparticles using the colloid according to claim 1 or 2 as a precursor or / and an intermediate.
As an inorganic compound, a mixture of ferrous sulfate heptahydrate and ferric chloride hexahydrate is used, and sodium hydroxide is added to the deoxygenated aqueous solution to make it into a colloidal form to suppress the reaction caused by heat. The method for producing inorganic nanoparticles using the colloid according to any one of claims 1 to 3 as a precursor or / and an intermediate, wherein the temperature is 5 ° C or lower.
The method for producing inorganic nanoparticles using colloid as a precursor or / and an intermediate according to claim 4, wherein sodium hydroxide is added to maintain the pH at 12 or more.