JP7045013B2 - Method for producing guanine crystals - Google Patents

Description

The present invention relates to a method for producing a guanine crystal, and more particularly to a method for producing a desired artificial guanine crystal from a guanine strong base salt aqueous solution by controlling the pH and using an additive.

Conventionally, biologically-derived guanine crystals have been used as fish scale foils in cosmetics because of their excellent light resistance and heat resistance, and as natural food additives because they are non-toxic.
In recent years, the layered structure of crystal plates derived from aquatic organisms has attracted attention as photonic crystals, of which guanine crystals derived from organisms have high reflectance and transparency, and thus have high light reflection. As a bioreflector, which is a material with a function, it is expected to be applied to optical devices.
However, since biological guanine crystals are expensive, processes for artificially obtaining guanine crystals are being developed in order to enable stable supply at low cost.
Non-Patent Document 1 describes that flat crystals are produced by recrystallization of guanine, and that organic and inorganic compounds are added to the solution to control the crystal morphology. It is as small as about 1 micron, and the recrystallized ones are aggregated.
Non-Patent Document 2 describes that guanine crystals are dissolved and recrystallized by adjusting the pH of the solution, but there are problems such as low guanine solubility and long crystallization. ..
Patent Document 1 describes that a guanine crystal powder is dissolved in a strongly basic solution to generate a base solution, then a trigger solution containing sodium and chlorine is added, and then the mixture is allowed to stand to precipitate guanine crystals. Has been done. It is also described that by adding a chromatophore obtained from fish, high-intensity guanine crystals having high reflectance in various directions can be rapidly produced.

Japanese Unexamined Patent Publication No. 2019-31478

Yuya Oaki, et al., "Morphology and orientation control of guanine crystal: a biogenic architecture and its structure mimetics", Journal of Materials Chemistry, 2012,22,22686-22691 Dvir Gur, et al., “Guanine Crystallization in Aqueous Solutions Enables Control over Crystal Size and Polymorphism”, Crystal Growth and Design, pp.4975-4980, Sep. 2016

Conventionally, as a method for artificially obtaining guanine crystals, a method in which guanine powder is dissolved in an alkaline solution and recrystallized by controlling the pH to obtain guanine crystals has been usual. However, guanine has low solubility even in an alkaline solution and cannot be made high in concentration, resulting in poor production efficiency. Further, the produced guanine crystals are aggregated, and the crystals grow like needles, so that it is not possible to obtain a plate-like crystal having a size of several tens of microns like a guanine crystal obtained from a fish or the like. Further, the optical characteristics of the obtained crystals could not realize the optical characteristics of the guanine crystals obtained from fish and the like.
Therefore, an object of the present invention is to obtain an artificial crystal having performance and uniform characteristics equal to or higher than those of a natural guanine crystal.

As a result of diligent studies to solve the above problems, the present inventor forms a guanine strong basic salt from guanine powder as a raw material, and uses the solution to control the pH and use an additive to obtain a desired artificial product. They have found that guanine crystals can be obtained, and have completed the present invention.

That is, the present invention relates to the following invention.
(1) A method for producing guanine crystals, which comprises a step of mixing a guanine strong base salt aqueous solution with an aqueous solution adjusted to pH 13-7.
(2) 1) A step of dissolving guanine crystal powder in a strong base solution having a pH of 14 or higher to produce a guanine strong base salt.
2) A step of precipitating, precipitating and isolating guanine strong base salt crystals by adding a common cation with the strong base to the solution containing the guanine strong base salt obtained in the above step, and 3). A method for producing a guanine crystal, which comprises a step of mixing an aqueous solution obtained by dissolving the strong guanine base salt crystal obtained in the above step in water and an aqueous solution adjusted to pH 13-7.
(3) The guanine according to (1) or (2), which comprises adjusting the pH of the mixed solution to a predetermined value in the step of mixing the guanine strong base salt aqueous solution with the aqueous solution adjusted to pH 13-7. Crystal manufacturing method.
(4) The method for producing a guanine crystal according to any one of (1) to (3), wherein the aqueous solution adjusted to pH 13 to 7 contains a buffer.
(5) One or 2 selected from inorganic salts, organic salts, proteins, saccharides, amino acids, nucleobases, surfactants and dispersants in the guanine strong base salt aqueous solution and / or the aqueous solution adjusted to pH 13-7. The method for producing a guanine crystal according to any one of (1) to (4), which comprises adding a water-soluble substance of seeds or more.
(6) The method for producing a guanine crystal according to any one of (1) to (5), which comprises heating the aqueous guanine strong base salt solution in a step of mixing the aqueous solution with the aqueous solution adjusted to pH 13 to 7.
(7) The method for producing a guanine crystal according to any one of (1) to (6), wherein the strong base is a compound containing sodium or potassium.

Crystals on the order of sub mm to sub μm can be produced by precipitating crystals by controlling the pH via a water-soluble strong base salt of guanine. Further, since the morphology and characteristics of the crystal can be controlled by adjusting the pH and temperature and various additives, it has become possible to obtain an artificial guanine crystal having a desired crystal form.
Further, since the concentration of the solution at the time of guanine crystallization can be made high, the production efficiency is good, and there are advantages such as being able to produce guanine crystals at a low pH (13 to 7).

The guanine crystals obtained in Example 1 (photo on the left) and the guanine crystals obtained in Example 1 were photographed with a telecentric microscope using a white LED lamp as a light source to photograph the movement state of the crystals when a magnetic field was applied. It is a photograph (the photograph on the right). A guanine crystal (Example 2) obtained when an aqueous solution containing a strong guanine base salt was added dropwise to an aqueous solution whose pH was adjusted to 9 with ammonium chloride was photographed with a telecentric microscope using a white LED lamp as a light source. It is a photograph. It is a photograph of a guanine crystal (Example 2) obtained when an aqueous solution containing a strong guanine base salt was heated to 45 ° C. and dropped by a telecentric microscope using a white LED lamp as a light source. It is a photograph of a guanine crystal (Example 3) obtained when an aqueous solution containing a strong guanine base salt was added dropwise to an aqueous solution having a pH of 12, taken with a telecentric microscope using a white LED lamp as a light source. It is a photograph of a guanine crystal (Example 4) obtained when an aqueous solution containing a strong guanine base salt was dropped into an aqueous solution to which calcium chloride was added, taken with a telecentric microscope using a white LED lamp as a light source. A photograph of a guanine crystal (Example 4) obtained when an aqueous solution containing a strong guanine base salt was added dropwise to an aqueous solution containing calcium chloride and sodium glutamate, taken with a telecentric microscope using a white LED lamp as a light source. Is. A photograph of a guanine crystal (Example 4) obtained when an aqueous solution containing a strong guanine base salt was added dropwise to a fish skin and an aqueous solution containing sodium glutamate, taken with a telecentric microscope using a white LED lamp as a light source. Is. The guanine crystal (Example 4) obtained when an aqueous solution containing a strong guanine base salt was dropped onto a fish skin and an aqueous solution containing sodium glutamate was irradiated with a blue LED lamp from an angle, and a telecentric microscope was used. This is a dark field photograph taken. It is a photograph of a guanine crystal (Example 5) obtained by using potassium hydroxide as a strong base when preparing a guanine strong base salt, taken with a telecentric microscope using a white LED lamp as a light source.

The present invention is a method for producing a guanine crystal, which comprises a step of mixing an aqueous solution containing a strong guanine base salt with an aqueous solution adjusted to pH 13-7. By the method of the present invention, the crystal shape, characteristics and the like can be controlled.
This will be described in detail below.

(1) Production of guanine strong base salt and its aqueous solution The guanine strong base salt and its aqueous solution can be specifically obtained through the following steps 1) to 3).
1) Dissolve guanine crystal powder in a strong base solution with a pH of 14 or higher to produce a guanine strong base salt.
2) By adding a common cation with the strong base to the solution containing the guanine strong base salt obtained in the above step, guanine strong base salt crystals are precipitated, precipitated and isolated, and 3) the above step. The guanine strong base salt crystals obtained in the above are dissolved in water.

For the solution containing the guanine strong base salt obtained in 1) above, more specifically, guanine crystal powder is added to a strong base solution having a pH of 14 or higher, and then water is added to the creamy liquid obtained by stirring. It can be manufactured by dissolving.
As the "guanine crystal powder", a commercially available guanine crystal powder manufactured by Wako Pure Chemical Industries, Ltd., for example, can be used.
As the "strong base solution having a pH of 14 or higher", an aqueous solution of a strong base can be used. Examples of the strong base include hydroxides of alkali metals such as LiOH, NaOH and KOH, and tetraalkylammonium hydroxide such as tetramethylammonium hydroxide and tetraethylammonium hydroxide.
The water used in the present invention is not particularly limited in all steps as long as the effect of the present invention is not impaired, and may be drinking water such as tap water and well water, but distilled water and pure water. , Ultrapure water is preferable.
The amount of the "strong base solution having a pH of 14 or higher" to be mixed with the "guanine crystal powder" may be an amount within a range in which the produced guanine strong base salt can be dissolved, and is usually 1 for 1 mol of the guanine crystal powder. It is not efficient to use a strong base solution having a pH of 14 or more and containing a strong base having a molar concentration or more and a saturation concentration of 10 times or more.

The "common cation with a strong base" added to a solution containing a guanine strong base salt to precipitate guanine strong base salt crystals means a compound having the same cation as the cation of the compound which is a strong base. do.
For example, when the strong base is NaOH, in addition to NaOH, sodium salts of strong acids such as NaCl, NaBr, and Na ₂ SO ₄ having Na ions can be mentioned. When the strong base is KOH, in addition to KOH, potassium salts of strong acids such as KCl, _{KBr, and K2 SO 4 can} be mentioned. When the strong base is tetraalkylammonium hydroxide, examples thereof include ammonium salts of strong acids such as NH ₄ Cl and (NH ₄ ) ₂ SO ₄ in addition to tetraalkylammonium hydroxide.
In particular, compounds containing sodium or potassium are preferred.
The amount of the "common cation with the strong base" to be added to the solution containing the guanine strong base salt may be an amount within the range in which the guanine strong base salt crystals can be precipitated, and is added according to Le Chatelier's law. It can be predicted from the solubility product of "common cations with strong bases". Usually, in the case of sodium guanine salt, 0.1 mol to 5 mol of "common cation with a strong base" is used for 1 mol.

The guanine strong base salt crystals precipitated by adding "common cations with strong bases" are dissolved in water after isolation. At this time, the amount of water is adjusted so that the pH becomes 14 or more. When 1 g of guanine strong base salt crystals is dissolved in 50 ml or less of water, the pH becomes 14 or more.
Further, when dissolving guanine strong base salt crystals in water, one or more of various additives can be added to water.

The additive is not particularly limited as long as it is a water-soluble material, and water-soluble materials belonging to inorganic salts, organic salts, water-soluble proteins, saccharides, amino acids, nucleobases, surfactants, dispersants and the like can be used. Can be mentioned. In addition, solid materials such as fish skins to which proteins, sugars, and other water-soluble organic substances are attached to the skins and the like can also be used.
Inorganic salts, organic salts, water-soluble proteins, saccharides, amino acids, nucleobases and the like can control the crystal morphology of guanine, and surfactants, dispersants and the like can prevent aggregation of the guanine crystals produced. ..

Examples of the inorganic salts include hydrochlorides of alkali metals and alkaline earth metals, sulfates, hydrogen sulfites, carbonates, hydrogen carbonates, phosphates, borates and the like, and examples thereof include sodium sulfate and sodium chloride. Examples thereof include potassium chloride, sodium carbonate, calcium chloride, magnesium sulfate and the like. These can be used alone or in combination of two or more.
Examples of the organic salts include organic acid salts of alkali metals and alkaline earth metals, and examples thereof include sodium acetate, potassium acetate, magnesium succinate, sodium benzoate, sodium citrate, and sodium ascorbate. These can be used alone or in combination of two or more.
Examples of the water-soluble protein include casein, gelatin, albumin, and denatured products of collagen. These can be used alone or in combination of two or more.
Examples of saccharides include starch decomposition products such as dextrin; sugars such as lactose, glucose, fructose, sugar, xylose and trehalose: sugar alcohols such as xylitol, erythritol, sorbitol, maltitol, lactitol and mannitol; , Oligosaccharides such as fructo-oligosaccharides and the like. These can be used alone or in combination of two or more.
As amino acids, basic amino acids such as lysine, arginine and histidine; acidic amino acids such as aspartic acid and glutamic acid; alkali metal salts of amino acids such as glutamic acid monosodium salt and aspartic acid monopotassium salt; 2-methylglutamic acid and 3-hydroxy Examples thereof include amino acid derivatives such as aspartic acid and N-methyltaurine. These can be used alone or in combination of two or more.
Examples of nucleobases include hypoxanthine and cytosine. These can be used alone or in combination of two or more.

As the surfactant, any of anion, cation, amphoteric, and nonionic can be used.
Examples of the anionic surfactant include monoalkyl sulfate, alkylpolyoxyethylene sulfate, alkylbenzene sulfonate, monoalkyl phosphate and the like.
Examples of the cationic surfactant include an alkyltrimethylammonium salt, a dialkyldimethylammonium salt, an alkylbenzyldimethylammonium salt and the like.
Examples of the amphoteric tenside agent include alkyldimethylamine oxide and alkylcarboxybetaine.
Examples of the nonionic surfactant include polyoxyethylene alkyl ether, fatty acid sorbitan ester, alkyl polyglucoside, fatty acid diethanolamide, and alkyl monoglyceryl ether.
Dispersants include carboxylic acid dispersants such as polyacrylic acid and its salts, polymethacrylic acid and its salts, polyacrylic acid copolymers and their salts, and polystyrene sulfonic acid and its salts; complex such as alkylimidazoline compounds. Ring-based dispersants; sulfonic acid, dodecylbenzenesulfonic acid, ligninsulfonic acid, sulfonic acid-based dispersants such as salts thereof; orthosilicic acid, metasilicic acid, fumic acid, tannic acid, dodecylsulfate and the like.
These additives are added to an aqueous solution containing a strong guanine base salt in an amount of 0.01 to 10% by weight in the case of a surfactant, a dispersant or the like . In the case of inorganic salts, organic salts, water-soluble proteins, saccharides, amino acids, nucleobases and the like, it is added in the range of 0.01% to a saturated concentration.

(2) Production of Guanine Crystals Guanine crystals can be produced by mixing the guanine strong base salt aqueous solution obtained in the above step with an aqueous solution adjusted to any of pH 13 to 7. The crystal grain size and shape can be changed depending on the pH. Therefore, the pH is set to any of 13 to 7 according to the purpose.
The pH of the aqueous solution can be adjusted to 13 to 7, by adding an acid, an alkali, salts thereof, or the like.
Examples of the mixing method include a method of dropping a guanine strong base salt aqueous solution into an aqueous solution adjusted to pH 13 to 7, a method of dividing the guanine strong base salt aqueous solution and mixing it with an aqueous solution adjusted to pH 13 to 7.
The amount of the aqueous solution adjusted to pH 13 to 7 is usually 1 to 1000 times the amount of the guanine strong base salt aqueous solution.
Further, one or more of various additives similar to those used when dissolving guanine strong base salt crystals in water can be added to the aqueous solution adjusted to pH 13 to 7.
These additives are added to the aqueous solution adjusted to pH 13 to 7 so as to be 0.01 to 10% by weight in the case of a surfactant, a dispersant and the like. In the case of inorganic salts, organic salts, water-soluble proteins, saccharides, amino acids, nucleobases, etc., add in the range of 0.01% to saturated concentration.

Further, after mixing the strong base salt aqueous solution of guanine with the aqueous solution adjusted to pH 13 to 7, the pH of the mixed solution can be adjusted to a predetermined value by using an acid, an alkali, salts thereof and the like. The crystal grain size and shape can be changed by adjusting the pH.
An appropriate amount of a buffer may be added to the aqueous solution adjusted to pH 13 to 7 in order to maintain the pH.
Examples of the buffer include borate buffer, phosphate buffer, carbonic acid buffer, citric acid buffer, acetate buffer and the like. These can be added alone or in combination of two or more.
As a borate buffer, boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borosand, etc.); as a phosphate buffer, phosphate or a salt thereof (disodium hydrogen phosphate). , Sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.); , Sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium hydrogencarbonate, magnesium carbonate, etc.); Citric acid or a salt thereof (sodium citrate, potassium citrate, calcium citrate, dihydrogen citrate) as a citrate buffer. Sodium, disodium citrate, etc.); Examples of the acetate buffer include acetic acid or a salt thereof (ammonium acetate, potassium acetate, calcium acetate, sodium acetate, etc.).

In the step of mixing the strong base salt aqueous solution of guanine with the aqueous solution adjusted to pH 13 to 7, heating can be performed, and it is preferable to heat at about 70 ° C. or lower. The temperature can be appropriately set depending on the type of additive to be mixed and the like. The crystal grain size and shape can be changed depending on the temperature.
Depending on the size and shape of the target crystal, the time for mixing the strong base salt aqueous solution of guanine and the aqueous solution adjusted to pH 13 to 7, the selection of additives, the temperature, and the final pH can be set.
The precipitated guanine crystals can be separated from the solution by filtration or the like, and then washed with water or the like for purification.

The isolated guanine crystal can be confirmed by a Fourier transform infrared spectrophotometer (FT-IR), X-ray diffraction (XRD), or the like.
With respect to the solution in which guanine crystals are precipitated, it is possible to observe the morphology with an optical microscope, observe the movement state of the crystals when a magnetic field is applied, and / or observe the interference fringes and reflections due to light irradiation.

Examples of the present invention are shown below, but the technical scope of the present invention is not limited thereto.
(Example 1)
Caustic soda: 2 g was dissolved in 10 ml, 3 g of commercially available guanine was added, and the mixture was stirred well to obtain a creamy solution. Further, 25 ml of water is added to make an aqueous solution of guanine sodium salt. Two grains of caustic soda were added to this aqueous solution to obtain crystals of sodium guanine.
0.85 g of guanine sodium salt crystals were taken in 200 ml of ultrapure water at pH 7 stirred at 120 rpm, and a solution dissolved in 30 ml of ultrapure water was added dropwise over 15 minutes. At this time, a 1N-HCl solution was used to adjust the pH so that the pH did not exceed 11. After the dropping was completed, the pH was set to 10 and the mixture was left to stand. Precipitation occurred immediately after the start of leaving, and the supernatant became transparent after leaving for 1 day. After leaving it at pH 8 for another day, it was filtered and washed to obtain a precipitate. The precipitate obtained was 0.84 g. FIG. 1 (photograph on the left) shows a photograph of crystals observed with a telecentric microscope using a white LED lamp as a light source. It was confirmed that the obtained crystals were rice granules and rotated 90 ° when a vertical magnetic field was applied with a magnet of about 150 mT (photo on the right).

(Example 2)
In Example 1, when the guanine sodium salt solution was added dropwise to the ultrapure water solution having a pH of 7, the following conditions 1) and 2) were carried out to precipitate crystals. FIGS. 2 and 3 show micrographs of a telecentric system using the obtained crystal white LED lamp as a light source.
1) Adjusted to pH 9 with ammonium chloride (Fig. 2).
The obtained crystal has a larger aspect ratio than that of Example 1.
2) Heated to 45 ° C (Fig. 3)
The obtained crystals show a columnar morphology as compared with Example 1.

(Example 3)
The step of obtaining the guanine sodium salt is the same as in Example 1.
0.35 g of guanine sodium salt crystals were taken in a 200 ml ultrapure water solution adjusted to pH 12 with caustic soda stirred at 120 rpm, and a solution dissolved in 30 ml ultrapure water was added dropwise over 20 minutes. At this time, a 1N-HCl solution was used to adjust the pH to 12. After the dropping was completed, stirring was stopped and the mixture was left to stand. Precipitation was confirmed from about 2 hours after the start of leaving. After 3 days, the pH was adjusted to 8, and after being left for another 1 day, the mixture was filtered and washed to obtain a precipitate. The precipitate obtained was 0.34 g. FIG. 4 shows a photograph taken by a telecentric microscope using the obtained crystal white LED lamp as a light source. The crystals were plate-like and moire-like striped patterns could be observed.

(Example 4)
In Example 3, the additives of 3) to 5) were added to the ultrapure water solution adjusted to pH 12, and crystals were precipitated. FIGS. 5 to 7 show micrographs of a telecentric system using the obtained crystal white LED lamp as a light source.
3) Calcium chloride (Fig. 5)
The crystal diameter was smaller than that of the crystal before the addition (Fig. 4), but a moire-like striped pattern could be observed.
4) Calcium chloride and monosodium glutamate (Fig. 6)
The particles were small and uniform rice particles.
5) Fish skin and monosodium glutamate (Fig. 7)
FIG. 8 shows a dark-field photograph of a telecentric microscope irradiated with a blue LED lamp from an oblique angle of the obtained crystal. Crystals with high reflection intensity have been obtained.

(Example 5)
In Example 2, potassium hydroxide was used as a strong base to be used when preparing a strong guanine base salt, and guanine crystals were precipitated. FIG. 9 shows a telecentric micrograph using the obtained crystal white LED lamp as a light source. The distribution of the particle size of the obtained crystals was wide, but the crystals were plate-like and moire-like stripes could be observed.

According to the present invention, it is expected to mass-produce uniform guanine crystals having a controlled shape. Therefore, it can be applied not only to functional devices such as bioreflectors (attitude control by water / magnetism) and optical devices (spectroscopy of minute parts by moire), but also to applications that consume a large amount of guanine crystals as cosmetics.

Claims (12)

A step of dissolving guanine strong base salt crystals in water to obtain a guanine strong base salt aqueous solution, and
A method for producing guanine crystals, which comprises a step of mixing the guanine strong base salt aqueous solution with an aqueous solution adjusted to pH 13-7 . The method for producing a guanine crystal according to claim 1, wherein the guanine strong base salt aqueous solution is obtained by the following steps 1), 2) and 3).
1) A step of dissolving guanine crystal powder in a strong base solution having a pH of 14 or higher to produce a guanine strong base salt.
2) A step of precipitating, precipitating and isolating guanine strong base salt crystals by adding a common cation with the strong base to the solution containing the guanine strong base salt obtained in the step 1). as well as
3) A step of dissolving the guanine strong base salt crystals obtained in the step 2) above in water. The method for producing a guanine crystal according to claim 1 or 2, wherein the pH of the guanine strong base salt aqueous solution is set to 14 or more. The invention according to any one of claims 1 to 3, wherein the pH of the mixed solution is adjusted to a predetermined value in the step of mixing the guanine strong base salt aqueous solution with the aqueous solution adjusted to pH 13 to 7. Method for producing guanine crystals. The method for producing guanine crystals according to claim 4, wherein the pH of the mixed solution is maintained at a constant value. The method for producing guanine crystals according to claim 4 or 5, wherein the pH of the mixed solution is adjusted with an acid or an alkali or salts thereof. The invention according to any one of claims 1 to 6, wherein the guanine strong base salt aqueous solution is added dropwise to an aqueous solution adjusted to pH 13 to 7, or divided and mixed with an aqueous solution adjusted to pH 13 to 7. How to make guanine crystals. The method for producing a guanine crystal according to any one of claims 1 to 7, wherein the aqueous solution adjusted to pH 13 to 7 contains a buffer. One or more selected from inorganic salts, organic salts, proteins, saccharides, amino acids, nucleobases, surfactants and dispersants in the guanine strong base salt aqueous solution and / or the aqueous solution adjusted to pH 13-7. The method for producing a guanine crystal according to any one of claims 1 to 8, wherein a water-soluble substance is added. The method for producing a guanine crystal according to any one of claims 1 to 9, wherein the guanine strong base salt aqueous solution is heated in the step of mixing the aqueous solution adjusted to pH 13 to 7. The method for producing a guanine crystal according to any one of claims 1 to 10, wherein the strong base is a compound containing sodium or potassium or tetraalkylammonium hydroxide. The compound added as a common cation with the strong base contains a strong acid salt or a tetraalkylammonium hydroxide or an ammonium salt of a strong acid having a cation of sodium hydroxide, potassium hydroxide or any of these compounds. The method for producing a guanine crystal according to claim 2 to 11 , which is characterized by the above-mentioned method.

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