Radical generating catalyst, method for producing radicals, method for producing oxidation reaction products, pharmaceuticals, and agricultural and livestock pharmaceuticals

Abstract

To provide a radical generating catalyst capable of generating radicals under mild conditions.SOLUTION: There is provided a first radical generating catalyst which contains at least one selected from the group consisting of an amino acid, a peptide, a phospholipid and salts thereof. There is provided a second or third radical-generating catalyst which contains an ammonium salt represented by the formula: N+(R11)(R21)(R31)(R41)X- and the Lewis acidity of the ammonium salt is 0.4 eV or more. Wherein, R11, R21, R31 and R41 are a hydrogen atom or an aromatic ring or an alkyl group, respectively, the alkyl group may contain an ether bond, a carbonyl group, an ester bond, or an amide bond, or an aromatic ring and two or more of R11, R21, R31 and R41 may integrated to form a ring together with N+ to which they are bonded.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a radical-generating catalyst, a method for producing radicals, a method for producing oxidation reaction products, a drug, and an agricultural and livestock drug. [Background technology]

[0002] Radicals are important and widely used chemical species due to their high reactivity. For example, sodium chlorite (NaClO2) is a non-toxic and inexpensive oxidizing reagent, and radical chlorine dioxide (ClO2 · ) have been used as precursors for (Non-Patent Documents 1 to 4). [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] H. Dodgen and H. Taube, J. Am. Chem. Soc., 1949, 71, 2501-2504. [Non-patent document 2] JK Leigh, J. Rajput, and DE Richardson, Inorg. Chem., 2014, 53,6715-6727. [Non-patent document 3] CL Latshaw, Tappi, 1994, 163-166. [Non-patent document 4] (a) JJ Leddy, in Riegel's Handbook of Industrial Chemistry, 8th edn. Ed., JA Kent, Van Nostrand Reinhold Co. Inc, New York, 1983, pp. 212-235; (b) I. Fabian, Coord. Chem. Rev., 2001, 216-217, 449-472. Summary of the Invention [Problem to be solved by the invention]

[0004] However, in general, a large amount of energy is required to generate radicals, which requires heating to a high temperature, which poses problems in terms of cost and reaction control.

[0005] Therefore, an object of the present invention is to provide a radical-generating catalyst capable of generating (producing) radicals under mild conditions, a method for producing radicals using the radical-generating catalyst, a method for producing oxidation reaction products using the method for producing radicals, a pharmaceutical, and an agricultural and livestock drug. [Means for solving the problem]

[0006] In order to achieve the above object, the first radical-generating catalyst of the present invention is characterized by containing at least one selected from the group consisting of amino acids, proteins, peptides, phospholipids, and salts thereof.

[0007] The second radical-generating catalyst of the present invention contains an ammonium salt (excluding peroxodisulfate) represented by the following chemical formula (XI), and the Lewis acidity of the ammonium salt is 0.4 eV or more: In a non-acidic liquid, catalyzes the generation of radicals from a radical generating source; The radical generating source is at least one selected from the group consisting of a halous acid, a halous acid ion, and a halous acid salt. [ka] In the chemical formula (XI), R 11 , R 21 , R 31 , and R 41 , each represent a hydrogen atom or an aromatic ring, or an alkyl group, and the alkyl group may contain an ether bond, a carbonyl group, an ester bond, an amide bond, or an aromatic ring; R 11 , R 21 , R31 , and R 41 may be the same or different, Or, R 11 , R 21 , R 31 , and R 41 Two or more of these are united and bonded together. + may form a cyclic structure together with the ring, and the cyclic structure may be saturated or unsaturated, may be aromatic or non-aromatic, and may or may not have one or more substituents; X - is an anion (excluding peroxodisulfate).

[0008] A third radical-generating catalyst of the present invention comprises an ammonium salt represented by the following chemical formula (XI), and the Lewis acidity of the ammonium salt is 0.4 eV or more: catalyzing radical generation from a radical generating source in the presence of an oxidizing agent; the oxidizing agent is O2, The radical generating source is at least one selected from the group consisting of a nitrogen-containing aromatic cation derivative represented by any one of the following formulas (A-1) to (A-8), a 9-substituted acridinium ion represented by the following formula (A-9), a quinolinium ion derivative represented by the following formula (I), stereoisomers and tautomers thereof, and salts thereof. [ka] In the chemical formula (XI), R 11 , R 21 , R 31 , and R 41 , each represent a hydrogen atom or an aromatic ring, or an alkyl group, and the alkyl group may contain an ether bond, a carbonyl group, an ester bond, an amide bond, or an aromatic ring; R 11 , R 21 , R 31 , and R 41 may be the same or different, Or, R11 , R 21 , R 31 , and R 41 Two or more of these are united and bonded together. + may form a cyclic structure together with the ring, and the cyclic structure may be saturated or unsaturated, may be aromatic or non-aromatic, and may or may not have one or more substituents; X - is an anion. [ka] [ka] [ka] In the formulas (A-1) to (A-8) and (A-9), R is a hydrogen atom or any substituent; Ar is the electron-donating group, and may be one or more, and when there are more than one, they may be the same or different; The nitrogen-containing aromatic ring forming the nitrogen-containing aromatic cation may or may not have one or more optional substituents other than R and Ar, In the formula (I), R 1 is a hydrogen atom or an optional substituent, Ar 1 ~Ar 3 are each a hydrogen atom or the above electron-donating group, and may be the same or different; Ar 1 ~Ar 3 At least one of the groups is the electron-donating group.

[0009] In the following, the first radical-generating catalyst of the present invention, the second radical-generating catalyst of the present invention, and the third radical-generating catalyst of the present invention may be collectively referred to as the "radical-generating catalyst of the present invention."

[0010] In order to achieve the above object, the first method for producing radicals according to the present invention is characterized by including a mixing step of mixing the radical-generating catalyst of the present invention with a radical-generating source.

[0011] The second method for producing radicals in the present invention includes a mixing step of mixing a Lewis acid (excluding peroxodisulfate) having a Lewis acidity of 0.4 eV or more with a radical generating source; a reaction step of reacting the Lewis acid with the radical generating source in a non-acidic liquid, The radical generating source is at least one selected from the group consisting of a halous acid, a halous acid ion, and a halous acid salt.

[0012] The third method for producing radicals in the present invention includes a mixing step of mixing a Lewis acid having a Lewis acidity of 0.4 eV or more, O2, and a radical generating source; a reaction step of reacting the Lewis acid, the O2, and the radical generating source in a liquid, the Lewis acid is the third radical-generating catalyst of the present invention, The radical generating source is at least one selected from the group consisting of a nitrogen-containing aromatic cation derivative represented by any one of formulas (A-1) to (A-8), a 9-substituted acridinium ion represented by formula (A-9), a quinolinium ion derivative represented by formula (I), stereoisomers and tautomers thereof, and salts thereof.

[0013] The fourth method for producing radicals according to the present invention includes a mixing step of mixing a Lewis acid (excluding peroxodisulfate) having a Lewis acidity of 0.4 eV or more with a radical generating source; a reaction step of reacting the Lewis acid with the radical generating source in a liquid, the Lewis acid having a Lewis acidity of 0.4 eV or more contains an inorganic substance, The radical generating source is at least one selected from the group consisting of a halous acid, a halous acid ion, and a halous acid salt.

[0014] In the following, the first radical production method of the present invention, the second radical production method of the present invention, the third radical production method of the present invention, and the fourth radical production method of the present invention may be collectively referred to as the "radical production method of the present invention."

[0015] The method for producing an oxidation reaction product of the present invention further comprises the steps of: A method for producing an oxidation reaction product by oxidizing an oxidizable substance, comprising the steps of: a radical production step of producing the radical by the radical production method of the present invention; an oxidation reaction step in which the oxidized material is reacted with an oxidizing agent by the action of the radicals to generate the oxidation reaction product; The present invention is characterized by comprising:

[0016] The drug of the present invention comprises A radical generating catalyst and a radical generating source are included, The radical-generating catalyst is the radical-generating catalyst of the present invention.

[0017] The agricultural and livestock drug of the present invention comprises: A radical generating catalyst and a radical generating source are included, The radical-generating catalyst is the radical-generating catalyst of the present invention. [Effects of the Invention]

[0018] The radical-generating catalyst, radical generator, and radical-producing method of the present invention can generate (produce) radicals under mild conditions. Applications of the radical-generating catalyst, radical generator, and radical-producing method of the present invention include, for example, the method for producing an oxidation reaction product of the present invention, but are not particularly limited thereto, and the catalyst, radical generator, and radical-producing method of the present invention can be used in a wide range of applications. [Brief explanation of the drawings]

[0019] [Figure 1] Figure 1 shows UV+visible absorption spectra of NaClO2 (5.0 mM) taken at 0, 4, and 16 hours after mixing with Sc(OTf)3 (10 mM) in aqueous solution at 298 K. [Figure 2] Figure 2(a) shows the time profile of UV-Vis absorption at 358 nm for the formation of Sc3+(ClO2 ·) from the reaction of Sc(OTf)3 (10 mM) with NaClO2 (5.0 mM) in aqueous solution (0.20 M acetate buffer, pH 2.9) at 298 K. (b) is a quadratic plot. [Figure 3] Figure 3(a) shows the time profile of UV-Vis absorption at 358 nm for the consumption of Sc3+(ClO2 ·) in the presence of styrene (30–90 mM) in MeCN / H2O (1:1 v / v) solution at 298 K. (b) shows the plot of the pseudo-first-order rate constant versus styrene concentration. [Figure 4] Figure 4 shows EPR spectra of MeCN solutions measured at 298 K. (a) is the spectrum of a MeCN solution containing NaClO2 (0.10 mM) after refluxing at 353 K for 1 hour. (b) is the spectrum of a MeCN solution containing NaClO2 (0.10 mM) and CF3COOH (10 mM). (c) is the spectrum of a MeCN solution containing NaClO2 (0.10 mM) and Sc(OTf)3 (10 mM). [Figure 5] Figure 5 shows the bond lengths (Å) of the DFT-optimized structures calculated at the CAM-B3LYP / 6-311+G(d,p) level. (a) is ClO2 ·, (b) is H + ClO2 ·, and (c) is Sc3 + ClO2 ·. [Figure 6] FIG. 6 shows the H NMR spectra of the reaction of styrene (2.0 mM) with NaClO (20 mM) in aqueous MeCN solution (MeCN / H O 1:1 v / v) at room temperature (25° C.). [Figure 7]Figure 7 shows the H NMR spectra of a mixture of styrene (66 mM) and NaClO (200 mM) in CDCN / D0 (4:1 v / v) at 60 °C (333 K) for 0 and 25 hours. * denotes the peak derived from styrene oxide. [Figure 8] Figure 8 shows the H NMR spectra of a mixture of styrene (2.0 mM), NaClO (20 mM), and Sc(OTf) (30 mM) in CDCN / DO (1:1 v / v) at 25 °C after 0.6 and 17 hours. * and † indicate peaks attributable to 1-phenylethane-1,2-diol and 2-chloro-1-phenylethanol, respectively. [Figure 9] Figure 9 shows the H NMR spectra of styrene (2.0 mM), NaClO (20 mM), and CF3COOD (30 mM) in CD3CN / DO (1:1 v / v) after 0.5 and 17 hours. * and † indicate peaks from 1-phenylethane-1,2-diol and 2-chloro-1-phenylethanol, respectively. [Figure 10] Figure 10 shows the spin distributions of (a) H + ClO2 · and (b) Sc3 + ClO2 · calculated at the CAM-B3LYP / 6-311+G(d,p) level. [Figure 11] Figure 11(a) is a graph showing the time-dependent change in the UV+visible absorption spectrum of an oxygen-saturated solution of the cobalt(II) tetraphenylporphyrin complex Co(II)TPP ([CoTPP] = 9.0 × 10-6 M, [O2] = 13 mM) to which benzethonium chloride (Bzn+) was added. Figure 11(b) is a graph showing the time-dependent change in the increase in the 433 nm absorption band in Figure 11(a). [Figure 12] FIG. 12 is a diagram showing the structure of Bzn+ optimized by density functional calculations (B3LYP / 6-31G(d) level). [Figure 13] Figure 13 is a UV+visible absorption spectrum of NaClO2 (20 mM) taken after mixing with Sc(OTf)3 (40 mM) in aqueous solution at 298 K. [Figure 14] The graphs in Figure 14(a) to (c) show the time course of the reaction when 10-methyl-9,10-dihydroacridine (AcrH2) (1.4 mM) and sodium chlorite (NaClO2) (2.8 mM) were added to a deoxygenated acetonitrile / water (1:1 v / v) mixed solution. [Figure 15] The graphs in Figures 15(a) and (b) show the time course of the reaction when the same mixed solution as in Figure 14 was prepared and Bzn+ (0.56 mM) was further added. [Figure 16] The graphs in Figures 16(a) and (b) show the time course of the reaction when the same mixed solution as in Figure 15 was prepared and Sc(OTf)3 (3.0 mM) was further added. [Figure 17] FIG. 17 is a schematic diagram illustrating a presumed reaction mechanism in the oxygenation (oxidation) reaction from AcrH2 to 10-methylacridone. [Figure 18] Figure 18(a) shows UV-visible absorption spectra of the oxidation reaction of triphenylphosphine using NaClO2 and scandium triflate. Figure 18(b) shows the relationship between the initial concentration of Ph3P and the concentration of Ph3P=O produced in the reaction of Figure 18(a). [Figure 19] Figure 19 shows the H NMR spectra of a mixture of styrene (2.0 mM), NaClO (6.0 mM), and Sc(OTf) (5.6 mM) in CDCN / D0 (1:1 v / v) at 25 °C under an Ar atmosphere after 0 and 45 hours. [Figure 20] FIG. 20 shows the yield and other information for an example in which an oxidation reaction product (benzoic acid) was obtained by oxidizing a raw material aromatic compound (benzaldehyde) in acetonitrile in the presence of 9-mesityl-10-methylacridinium (Acr+-Mes) perchlorate (Acr+-Mes ClO4 -) and oxygen. [Figure 21] FIG. 21 is a graph showing the Lewis acidity of benzethonium chloride [Bzn+Cl-] and various metal complexes. [Figure 22]The UV-visible absorption spectra in Figure 22(a) show the conversion of triphenylphosphine to triphenylphosphine oxide over time, and the graph in Figure 22(b) shows the change in triphenylphosphine (Ph3P) concentration over time in the presence and absence of Sc(OTf)3 (Sc3+). [Figure 23] FIG. 23 is an ESR spectrum of the drug of the example. [Figure 24] FIG. 24 is an ESR spectrum of the drug of the example. [Figure 25] FIG. 25 is an ESR spectrum of the drug of the example. [Figure 26] FIG. 26 is an ESR spectrum of the drug of the example. [Figure 27] FIG. 27 is a graph showing the inhibitory effect of the agents of the examples on ulcerative colitis. [Figure 28] FIG. 28 is a graph showing changes in the intestinal bacterial flora caused by the drug of the example. DETAILED DESCRIPTION OF THE INVENTION

[0020] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following description.

[0021] [1. Radical-generating catalyst] The uses of the first to third radical-generating catalysts of the present invention are not particularly limited, and for example, as described above, they can be used in the first radical production method of the present invention. The first to third radical-generating catalysts of the present invention can also be used in the second to fourth radical production methods of the present invention. As described above, the second to fourth radical production methods of the present invention can use Lewis acids with a Lewis acidity of 0.4 eV or more. It is believed that the Lewis acids with a Lewis acidity of 0.4 eV or more function as radical-generating catalysts. Hereinafter, unless otherwise specified, the term "radical-generating catalyst of the present invention" is not limited to the first to third radical-generating catalysts of the present invention, but also includes Lewis acids with a Lewis acidity of 0.4 eV or more.

[0022] The radical generating catalyst of the present invention may be, for example, an organic compound or an inorganic substance. The organic substance may be, for example, at least one selected from the group consisting of ammonium, amino acids, peptides, phospholipids, and salts thereof. The inorganic substance may contain one or both of metal ions and nonmetal ions. The metal ions may contain one or both of typical metal ions and transition metal ions. The inorganic substance may be, for example, alkaline earth metal ions, rare earth ions, Sc 3+ , Li + , Fe 2+ , Fe 3+ , Al 3+ The alkaline earth metal ion may be at least one selected from the group consisting of calcium, strontium, barium, and radium ions. 2+ , Sr 2+ , Ba 2+ , and Ra 2+ "Rare earth" includes scandium 21 Sc, yttrium 39 Two elements, Y and lanthanum 57 La to Lutetium 71It is a general term for a total of 17 elements, including 15 elements (lanthanoids) up to Lu. Examples of rare earth ions include trivalent cations of each of the 17 elements.

[0023] The Lewis acid (including counter ions) may be at least one selected from the group consisting of CaCl2, MgCl2, FeCl2, FeCl3, AlCl3, AlMeCl2, AlMe2Cl, BF3, BPh3, BMe3, TiCl4, SiF4, and SiCl4, where "Ph" represents a phenyl group and "Me" represents a methyl group.

[0024] In the radical-generating catalyst of the present invention, the radical-generating catalyst can be appropriately selected depending on the purpose, taking into consideration the reactivity, acidity, safety, and the like.

[0025] As a result of their investigations, the present inventors have found that ammonium (particularly organic ammonium), amino acids, peptides, and phospholipids function as radical-generating catalysts. Furthermore, as a result of further investigations, the present inventors have found that ammonium, amino acids, peptides, and phospholipids that function as radical-generating catalysts sometimes have Lewis acid properties. That is, although the reason why ammonium, amino acids, peptides, and phospholipids function as radical-generating catalysts is unclear, it is presumed that this is because the ammonium, amino acids, peptides, and phospholipids function as Lewis acids. Furthermore, as a result of further investigations, the present inventors have found a radical-generating catalyst containing an organic compound that has at least one of Lewis acidity and Bronsted acidity. In the present invention, "Lewis acid" refers to, for example, a substance that acts as a Lewis acid with respect to the radical-generating source.

[0026] The Lewis acidity of the radical-generating catalyst of the present invention is, for example, 0.4 eV or more, 0.5 eV or more, or 0.6 eV or more. The upper limit of the Lewis acidity is not particularly limited, but is, for example, 20 eV or less. In the present invention, the criterion for determining whether the Lewis acidity is equal to or less than the above numerical value is, for example, whether the value measured by either the "Lewis acidity measurement method (1)" or the "Lewis acidity measurement method (2)" described below is equal to or less than the above numerical value.

[0027] The Lewis acidity can be measured by the method described in, for example, Ohkubo, K.; Fukuzumi, S. Chem. Eur. J., 2000, 6, 4532, J. AM. CHEM. SOC. 2002, 124, 10270-10271, or J. Org. Chem. 2003, 68, 4720-4726, and specifically, by the following "Method (1) for measuring Lewis acidity."

[0028] (Method for measuring Lewis acidity (1)) Cobalt tetraphenylporphyrin, saturated O2, and the object to be measured for Lewis acidity (e.g., a cation of a metal, etc., in the following chemical reaction formula (1a)) are n+ The change in the UV-visible absorption spectrum of acetonitrile (MeCN) containing the reaction product (represented by k cat ) can be used to calculate the ΔE value (eV), which is an index of Lewis acidity. cat The higher the value, the stronger the Lewis acidity. The Lewis acidity of an organic compound can also be estimated from the energy level of the lowest unoccupied molecular orbital (LUMO), calculated by quantum chemical calculations. The higher the positive value, the stronger the Lewis acidity.

[0029]

number

[0030] The following shows an example of the reaction rate constant between CoTPP and oxygen in the presence of a Lewis acid, which serves as an index of Lewis acidity measured (calculated) by the above-mentioned measurement method. cat ,M -2 s -1 " represents CoTPP and oxygen in the presence of a Lewis acid. "LUMO, eV" represents the LUMO energy level. "benzethonium chloride" represents benzethonium chloride, "benzalkonium chloride" represents benzalkonium chloride, "tetramethylammonium hexafluorophosphate" represents tetramethylammonium hexafluorophosphate, "tetrabutylammonium hexafluorophosphate" represents tetrabutylammonium hexafluorophosphate, and "ammonium hexafluorophosphate" represents ammonium hexafluorophosphate.

[0031] [Table tpp]

[0032] Furthermore, in the present invention, Lewis acidity may be measured by using ubiquinone 1 (Q1) instead of oxygen molecules (O2) in Lewis acidity measurement method (1) and reducing ubiquinone 1 to generate anion radicals of ubiquinone 1. Such a method for measuring Lewis acidity may be hereinafter referred to as "Lewis acidity measurement method (2)." In Lewis acidity measurement method (2), the measurement can be performed in the same manner as Lewis acidity measurement method (1) except that ubiquinone 1 (Q1) is used instead of oxygen molecules (O2). In addition, in Lewis acidity measurement method (2), the obtained reaction rate constant (k catThe ΔE value (eV), which is an index of Lewis acidity, can be calculated from the above. The method (2) for measuring Lewis acidity is described, for example, in Ohkubo, K.; Fukuzumi, S. Chem. Eur. J., 2000, 6, 4532, and can be performed according to or in accordance with the method described therein.

[0033] The Lewis acidity measurement method (2) is carried out by measuring the reaction rate constant (k cat ) can be measured.

number

[0034] The Lewis acidity of the radical-generating catalyst of the present invention can be determined, for example, by the reaction rate constant (k cat ) that is, the reaction rate constant (k cat ) measured value (K obs ) is, for example, 1.0×10 -5 S -1 That's it, 2.0 x 10 -5 S -1 That's it, 3.0 x 10 -5 S -1 That's it, 4.0 x 10 -5 S -1 That's it, 5.0 x 10 -5 S -1 That's it, 6.0 x 10 -5 S -1 That's it, 7.0 x 10 -5 S-1 Above, 8.0×10 -5 S -1 Above, 9.0×10 -5 S -1 Above, 1.0×10 -4 S -1 Above, 2.0×10 -4 S -1 Above, 3.0×10 -4 S -1 Above, 4.0×10 -4 S -1 Above, 5.0×10 -4 S -1 Above, 6.0×10 -4 S -1 Above, 7.0×10 -4 S -1 Above, 8.0×10 -4 S -1 Above, 9.0×10 -4 S -1 Above, 1.0×10 -3 S -1 Above, 2.0×10 -3 S -1 Above, 3.0×10 -3 S -1 Above, 4.0×10 -3 S -1 Above, 5.0×10 -3 S -1 Above, 6.0×10 -3 S -1 Above, 7.0×10 -3 S -1 Above, 8.0×10 -3 S -1 Above, 9.0×10 -3 S -1 Above, 1.0×10 -2 S -1 Above, 2.0×10 -2 S -1 Above, 3.0×10 -2 S -1 Above, 4.0×10 -2 S -1 Above, 5.0×10 -2 S -1 Above, 6.0×10 -2 S -1 Above, 7.0×10 -2 S -1 Above, 8.0×10-2 S -1 or more, or 9.0 x 10 -2 S -1 It may be 1.0 x 10 or more. -1 S -1 Below, 9.0 x 10 -2 S -1 Below, 8.0 x 10 -2 S -1 Below, 7.0 x 10 -2 S -1 Below, 6.0 x 10 -2 S -1 Below, 5.0 x 10 -2 S -1 Below, 4.0 x 10 -2 S -1 Below, 3.0 x 10 -2 S -1 Below, 2.0 x 10 -2 S -1 Below, 1.0 x 10 -2 S -1 Below, 9.0 x 10 -3 S -1 Below, 8.0 x 10 -3 S -1 Below, 7.0 x 10 -3 S -1 Below, 6.0 x 10 -3 S -1 Below, 5.0 x 10 -3 S -1 Below, 4.0 x 10 -3 S -1 Below, 3.0 x 10 -3 S -1 Below, 2.0 x 10 -3 S -1 Below, 1.0 x 10 -3 S -1 Below, 9.0 x 10 -4 S -1 Below, 8.0 x 10 -4 S -1 Below, 7.0 x 10 -4 S -1 Below, 6.0 x 10 -4 S -1 Below, 5.0 x 10 -4 S -1 Below, 4.0 x 10 -4 S -1 Below, 3.0 x 10 -4 S-1 Below, 2.0 x 10 -4 S -1 Below, 1.0 x 10 -4 S -1 Below, 9.0 x 10 -5 S -1 Below, 8.0 x 10 -5 S -1 or less, or 7.0 x 10 -5 S -1 It may be the following:

[0035] In the radical-generating catalyst of the present invention, the ammonium may be, for example, quaternary ammonium, or may be tertiary, secondary, primary, or zeroth ammonium. The ammonium is not particularly limited and may be, for example, a nucleic acid base, or an amino acid or peptide, which will be described later.

[0036] In the radical-generating catalyst of the present invention, the at least one selected from the group consisting of ammonium, amino acids, peptides, phospholipids, and salts thereof (first radical-generating catalyst of the present invention), or the compound having at least one of Lewis acidity and Bronsted acidity (second radical-generating catalyst of the present invention) may be, for example, a cationic surfactant or a quaternary ammonium-type cationic surfactant. Examples of quaternary ammonium-type cationic surfactants include benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, hexadecyltrimethylammonium bromide, dequalinium chloride, edrophonium, didecyldimethylammonium chloride, tetramethylammonium chloride, tetrabutylammonium chloride, benzyltriethylammonium chloride, oxitropium, carbachol, glycopyrronium, safranine, sinapine, tetraethylammonium bromide, hexadecyltrimethylammonium bromide, and suxamethoxazole. Examples of quaternary ammonium salts include niu, sphingomyelin, ganglioside GM1, denatonium, trigonelline, neostigmine, paraquat, pyridostigmine, phellodendrine, pralidoxime methyl iodide, betaine, betanin, bethanechol, betalain, lecithin, adenine, guanine, cytosine, thymine, uracil, and cholines (choline chlorides such as benzoylcholine chloride and lauroylcholine chloride hydrate, phosphocholine, acetylcholine, choline, dipalmitoylphosphatidylcholine, and choline bitartrate). However, in the radical production method of the present invention, the quaternary ammonium salt is not limited to surfactants.

[0037] In the radical-generating catalyst of the present invention, the ammonium may be, for example, ammonium represented by the following chemical formula (XI).

[0038] [ka]

[0039] In the chemical formula (XI), R 11 , R21 , R 31 , and R 41 , each represent a hydrogen atom or an aromatic ring, or an alkyl group, and the alkyl group may contain an ether bond, a carbonyl group, an ester bond, an amide bond, or an aromatic ring; R 11 , R 21 , R 31 , and R 41 may be the same or different, Or, R 11 , R 21 , R 31 , and R 41 Two or more of these are united and bonded together. + may form a cyclic structure together with the ring, and the cyclic structure may be saturated or unsaturated, may be aromatic or non-aromatic, and may or may not have one or more substituents; X - is an anion. X - is, for example, an anion excluding peroxodisulfate. R 11 , R 21 , R 31 , and R 41In the above, the aromatic ring is not particularly limited, and may or may not contain a heteroatom, and may or may not have a substituent. Examples of the aromatic ring containing a heteroatom (heteroaromatic ring) include a nitrogen-containing aromatic ring, a sulfur-containing aromatic ring, and an oxygen-containing aromatic ring. Examples of the aromatic ring not containing a heteroatom include a benzene ring, a naphthalene ring, an anthracene ring, and a phenanthrene ring. Examples of the heteroaromatic ring include a pyridine ring, a thiophene ring, and a pyrene ring. The nitrogen-containing aromatic ring may or may not have a positive charge, for example. Examples of the nitrogen-containing aromatic ring not having a positive charge include a pyrroline ring, a pyridine ring, a pyridazine ring, a pyrimidine ring, a pyrazine ring, a quinoline ring, an isoquinoline ring, an acridine ring, a 3,4-benzoquinoline ring, a 5,6-benzoquinoline ring, a 6,7-benzoquinoline ring, a 7,8-benzoquinoline ring, a 3,4-benzoisoquinoline ring, a 5,6-benzoisoquinoline ring, a 6,7-benzoisoquinoline ring, and a 7,8-benzoisoquinoline ring. Examples of the positively charged nitrogen-containing aromatic ring include a pyrrolinium ring, a pyridinium ring, a pyridazinium ring, a pyrimidinium ring, a pyrazinium ring, a quinolinium ring, an isoquinolinium ring, an acridinium ring, a 3,4-benzoquinolinium ring, a 5,6-benzoquinolinium ring, a 6,7-benzoquinolinium ring, a 7,8-benzoquinolinium ring, a 3,4-benzoisoquinolinium ring, a 5,6-benzoisoquinolinium ring, a 6,7-benzoisoquinolinium ring, a 7,8-benzoisoquinolinium ring, etc. Examples of the oxygen-containing aromatic ring or sulfur-containing aromatic ring include aromatic rings in which at least one carbon atom or nitrogen atom of the aromatic ring or nitrogen-containing ring not containing a heteroatom is replaced with at least one oxygen atom and / or sulfur atom. R 11 , R 21 , R 31 , and R 41 In the above formula, when the alkyl group or the aromatic ring has a substituent, the substituent is not particularly limited and may be any, and examples thereof include a sulfo group, a nitro group, and a diazo group.

[0040] The ammonium represented by the chemical formula (XI) may be, for example, ammonium represented by the following chemical formula (XII).

[0041] [ka]

[0042] In the chemical formula (XII), R 111 is an alkyl group having 5 to 40 carbon atoms, which may contain an ether bond, a ketone (carbonyl group), an ester bond, an amide bond, a substituent, or an aromatic ring, R 21 and X - is the same as the above chemical formula (XI). R 111 In the formula (I), the aromatic ring is not particularly limited, and may or may not contain a heteroatom, and may or may not have a substituent. 111 In the formula (XI), specific examples of the aromatic ring are not particularly limited, but include, for example, R 11 , R 21 , R 31 , and R 41 is the same as: R 111 In the case where the alkyl group or the aromatic ring has a substituent, the substituent is not particularly limited and is arbitrary. For example, R 11 , R 21 , R 31 , and R 41 is the same as:

[0043] In the chemical formula (XII), R 21may be, for example, a methyl group or a benzyl group, and the benzyl group may or may not have one or more hydrogen atoms of the benzene ring substituted with an optional substituent, and the optional substituent may be, for example, an alkyl group, an unsaturated aliphatic hydrocarbon group, an aryl group, a heteroaryl group, a halogen, a hydroxy group (—OH), a mercapto group (—SH), or an alkylthio group (—SR, where R is an alkyl group).

[0044] The ammonium salt represented by the chemical formula (XII) may be, for example, ammonium represented by the following chemical formula (XIII).

[0045] [ka]

[0046] In the chemical formula (XIII), R 111 and X - is the same as the above chemical formula (XII).

[0047] The ammonium represented by the chemical formula (XI) may be, for example, an ammonium salt represented by the following chemical formula (XIV).

[0048] [ka] In the chemical formula (XIV), R 100 may form a cyclic structure, which may be saturated or unsaturated, aromatic or non-aromatic, and may or may not have one or more substituents; R 11 and X - is the same as the above chemical formula (XI).

[0049] The ammonium salt represented by the chemical formula (XI) may be, for example, an ammonium salt represented by the following chemical formula (XV).

[0050] [ka]

[0051] In the chemical formula (XV), each Z is CH or N, and may be the same or different, and in the case of CH, H may be optionally substituted with a substituent; R 11 and X - is the same as the above chemical formula (XI).

[0052] The ammonium salt represented by the chemical formula (XI) may be, for example, an ammonium salt represented by the following chemical formula (XVI).

[0053] [ka]

[0054] In the chemical formula (XVI), R 101 , R 102 , R 103 , and R 104 are each a hydrogen atom or a substituent, and R 101 , R 102 , R 103 , and R 104 may be the same or different, Or, R 101 , R 102 , R 103 , and R 104 Two or more of these are united and bonded together. + may form a cyclic structure together with the ring, and the cyclic structure may be saturated or unsaturated, may be aromatic or non-aromatic, and may or may not have one or more substituents; Z is CH or N, and in the case of CH, H may be substituted by a substituent; R 11 and X - is the same as the above chemical formula (XI).

[0055] The ammonium salt represented by the chemical formula (XI) may be, for example, an ammonium salt represented by the following chemical formula (XVII).

[0056] [ka]

[0057] In the chemical formula (XVII), R 111 ~R 118 are each a hydrogen atom or a substituent, and R 111 ~R 118 may be the same or different, Or, R 111 ~R 118 Two or more of these may be integrated to form a ring structure, and the ring structure may be It may be an aromatic or non-aromatic ring, and may or may not have one or more substituents; Z is CH or N, and in the case of CH, H may be substituted by a substituent; R 11 and X - is the same as the above chemical formula (XI).

[0058] The ammonium salt represented by the chemical formula (XI) may be, for example, at least one selected from the group consisting of benzethonium chloride, benzalkonium chloride, hexadecyltrimethylammonium chloride, tetramethylammonium chloride, ammonium chloride, methylammonium chloride, and tetrabutylammonium chloride. It is particularly preferable that the ammonium salt represented by the chemical formula (XII) is benzethonium chloride.

[0059] In addition, benzethonium chloride (Bzn + Cl - ) can be represented by the following chemical formula: Furthermore, benzalkonium chloride can be represented by, for example, the following chemical formula: 111 is an alkyl group having 8 to 18 carbon atoms, and X -is the chloride ion. [ka]

[0060] In the chemical formulas (XI), (XII), (XIII), (XIV), (XV), (XVI), and (XVII), X - is any anion and is not particularly limited. - is not limited to a monovalent anion, and may be an anion of any valence, such as divalent or trivalent. When the anion has multiple charges, such as divalent or trivalent, the number of ammonium (monovalent) molecules in the chemical formulas (XI), (XII), (XIII), (XIV), (XV), (XVI), and (XVII) is, for example, the number of anion molecules multiplied by the anion valence (for example, when the anion is divalent, the number of anion (monovalent) molecules is twice the number of anion molecules). X - Examples of the ions include halogen ions (fluoride ions, chloride ions, bromide ions, iodide ions), acetate ions, nitrate ions, and sulfate ions.

[0061] In the present invention, the radical-generating catalyst is not limited to, for example, the formulas (XI), (XII), (XIII), (XIV), (XV), (XVI), and (XVII), and may be an ammonium of any structure containing an aromatic ring. The aromatic ring is not particularly limited, but for example, R 11 , R 21 , R 31 , and R 41 Examples of the aromatic ring include the aromatic rings exemplified in

[0062] In the present invention, the radical-generating catalyst may be, for example, a sulfonic acid amine or its ammonium. The sulfonic acid amine is, for example, an amine having a sulfo group (sulfonic acid group) in the molecule. Examples of the sulfonic acid amines include taurine, sulfamic acid, 3-amino-4-hydroxy-1-naphthalenesulfonic acid, sulfamic acid, p-toluidine-2-sulfonic acid, o-anisidine-5-sulfonic acid, Direct Blue 14, 3-[N,N-bis(2-hydroxyethyl)amino]-2-hydroxypropanesulfonic acid, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, aminomethanesulfonic acid, 3-sulfopropylamine, 2-aminobenzenesulfonic acid, R(+)-3-aminotetrahydrofuran toluene, 4-amino-5-hydroxy-1,7-naphthalenedisulfonic acid, N-(2-acetamido)-2-aminoethanesulfonic acid, sodium 4'-amino-3'-methoxyazobenzene-3-sulfonate, and lapatinib. Ditosylate, N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid, 8-amino-1,3,6-naphthalenetrisulfonic acid disodium salt hydrate, 1-aminonaphthalene-2-sulfonic acid, (2S,3S)-3-amino-2-methyl-4-oxo-1-azetidinesulfonic acid, 3-(1-naphthylamino)propanesulfonic acid sodium salt, 3-methyl-4-aminobenzenesulfonic acid, 3-cyclohexylamino-2-hydroxypropanesulfonic acid sodium salt, N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid sodium salt, 4-amino-1-naphthalenesulfonic acid, sodium sulfamate, tricaine, sodium sulfanilate, 1,4-phenylenediamine-2-sulfonic acid, p-anisidine-2-sulfonic acid, 6-amino-1-naphthalenesulfonic acid, 3,4-Diaminobenzenesulfonic acid, 3-amino-4-chlorobenzenesulfonic acid, 3-[(4-amino-3-methylphenyl)azo]benzenesulfonic acid, 3-amino-4-hydroxy-5-nitrobenzenesulfonic acid, 5-amino-6-hydroxy-3-nitrobenzenesulfonic acid, 4-acetamido-2-aminobenzenesulfonic acid hydrate, 2-aminophenol-4-sulfonic acid, 1-amino-2-methoxy-5-methyl-4-benzenesulfonic acid, dansylic acid, Sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl ester, 5-sulfo-4'-diethylamino-2,2'-dihydroxyazobenzene, 2-aminonaphthalene-6,8-disulfonic acid, sodium 2-[N,N-bis(2-hydroxyethyl)amino]-1-ethanesulfonate, 3-acetyl-2-(methylaminosulfonyl)thiophene, sodium 4-amino-2-chlorotoluene-5-sulfonate, 5-(3-AMINO-5-OXO-2-PYRAZOLIN-1-YL)-2-PHENOXYBENZENESULFONIC ACID, potassium sulfamate, P-AMINOAZOBENZENE MONOSULFONIC ACID, 3-[(3-Cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate, 3-amino-2,7-naphthalenedisulfonic acid monosodium salt, 3-[N,N-bis(hydroxyethyl)amino]-2-hydroxypropanesulfonic acid sodium salt, cobalt(II) di(amidosulfate), 3-(4-amino-3-methoxyphenylazo)benzenesulfonic acid, nickel(II) sulfamate tetrahydrate, sodium 2,4-diaminobenzenesulfonate, 5-amino-2-chlorotoluene-4-sulfonic acid, 2,5-dichlorosulfanilic acid, 4-methylbenzenesulfonic acid, APTS (aminopyrenetrisulfonic acid), 4'-aminoazobenzene-3-sulfonic acid, Pontacil carmine 2B, p-anisidine-3-sulfonic acid, 4,4'-Bis(4-amino-1-naphthylazo)-2,2'-stilbenesulfonic acid, 3-Aminonaphthalene-8-hydroxy-4,6-disulfonic acid, Sodium 4-amino-1,5-naphthalenedisulfonate, Sodium 4-aminoazobenzene-4'-sulfonate, 5-amino-2-methylbenzenesulfonic acid, Disodium 7-amino-1,3-naphthalenedisulfonate, Alizarin Sapfirol SE, 7-amino-2-naphthalenesulfonic acid Sodium, 6-amino-5-bromopyridine-3-sulfonic acid, 2-aminoethanethiol p-toluenesulfonate, sodium 2-amino-1-naphthalenesulfonate, 6-amino-1,3-naphthalenedisulfonic acid disodium salt hydrate, N,N,N',N'-tetraethylsulfamide, 5-amino-2-ethoxybenzenesulfonic acid, 3,5-diamino-2,4,6-trimethylbenzenesulfonic acid, 7-amino-1-naphthalenesulfonic acid, guanidine sulfamate, 2-amino-5-nitrobenzenesulfonic acid, nickel(II) diamido sulfate, 4-amino-4'-nitrostilbene-2,2'-disulfonic acid disodium, aniline-2,5-disulfonic acid monosodium, 5-amino-1-naphthol-3-sulfonic acid hydrate, 2,5-dichlorosulfanilic acid Sodium, 6-aminohexanoic acid hexyl p-toluenesulfonate, rac-(R*)-2-(4-chlorophenyl)-3-amino-1-propanesulfonic acid, 2-(N,N-dipropyl)amino anisole-4-sulfonic acid, 2-amino-4-chlorophenol-6-sulfonic acid, 6-amino-1,3-naphthalenedisulfonic acid, 5,10,15,20-tetrakis[4-(trimethylammonio)phenyl]-21H,-23H-porphine tetratosylate, 5-amino-2-[(4-aminophenyl)amino]benzenesulfonic acid, 4-amino-3-chlorobenzenesulfonic acid, 2-aminobenzenesulfonic acid phenyl ester, 4-acetylamino-4'-isothiocyanatostilbene-2,2'-disulfonic acid disodium salt, (S)-3-AMINO-2-OXETANONE P-TOLUENESULFONIC ACID SALT, 5-acetylamino-4-hydroxy-2,Examples include disodium 7-naphthalenedisulfonate, 2-phenylamino-5-aminobenzenesulfonic acid, sodium 4-octadecylamino-4-oxo-2-[(sodiumoxy)sulfonyl]butanoate, and 3,5-diamino-4-methylbenzenesulfonic acid.

[0063] In the present invention, the radical-generating catalyst may be, for example, a nicotinic amine or its ammonium. The nicotinic amine is, for example, an amine having a cyclic structure in the molecule, and the cyclic structure includes a nicotine skeleton. Examples of the nicotinic amine include nicotinamide and alkaloids.

[0064] In the present invention, the radical-generating catalyst may be, for example, a nitrite-based amine or a nitrite-based ammonium. The nitrite-based amine or nitrite-based ammonium is, for example, a compound obtained by reacting an amine with nitrous acid or a nitrous acid derivative. Examples of the nitrite-based amine or nitrite-based ammonium include diazo compounds, diazonium salts, N-nitroso compounds, and C-nitroso compounds.

[0065] In the present invention, the ammonium has an ammonium structure (N + Furthermore, the ammonium may be in the form of a dimer, a trimer, or the like, in which a plurality of molecules associate with each other through π electron interactions.

[0066] In the present invention, the amino acid is not particularly limited. For example, the amino acid may contain at least one amino group or imino group and at least one carboxy group in the molecule. The amino acid may be, for example, an α-amino acid, a β-amino acid, a γ-amino acid, or other amino acid. The amino acid may be, for example, a protein-constituting amino acid, specifically, at least one selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, glutamic acid, asparagine, glutamine, lysine, hydroxylysine, arginine, cysteine, cystine, methionine, phenylalanine, tyrosine, tryptophan, histidine, proline, and 4-hydroxyproline.

[0067] In the present invention, the peptide is not particularly limited. For example, the peptide may be one in which two or more of the amino acid molecules are bound by peptide bonds. For example, the peptide may be at least one of oxidized glutathione (GSSG) and reduced glutathione (GSH).

[0068] In the present invention, the phospholipid is not particularly limited. The phospholipid may be, for example, a lipid containing a phosphorus atom in the molecule, and may be, for example, a lipid containing a phosphate ester bond (POC) in the molecule. The phospholipid may or may not have, for example, at least one of an amino group, an imino group, an ammonium group, and an iminium group in the molecule. The phospholipid may be, for example, at least one selected from the group consisting of phosphatidylserine, phosphatidylcholine, phosphatidic acid, phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin.

[0069] The radical generator of the present invention may contain, for example, a Bronsted acid. a is, for example, 5 or more. aThe upper limit is not particularly limited, but is, for example, 50 or less.

[0070] The radical generating catalyst of the present invention may catalyze the generation of radicals from a radical generating source ex vivo, or may catalyze the generation of radicals from a radical generating source in vivo, for example, in the human body or in the body of an animal other than a human.

[0071] The radical-generating catalyst of the present invention may catalyze radical generation from a radical-generating source, for example, in the digestive organs. The digestive organs may be, for example, at least one selected from the group consisting of the oral cavity, pharynx, esophagus, stomach, duodenum, small intestine, and large intestine. The digestive organs may be, for example, the large intestine. The small intestine may be, for example, at least one selected from the group consisting of the duodenum, jejunum, and ileum. The large intestine may be, for example, at least one selected from the group consisting of the cecum, colon, and rectum. The radical-generating catalyst of the present invention may be used, for example, for sterilizing the digestive organs, inducing changes in the intestinal flora, treating ulcerative colitis, or suppressing symptoms.

[0072] [2. Radical Production Method] Next, the method for producing radicals of the present invention will be explained.

[0073] As described above, the method for producing radicals in the present invention includes a mixing step of mixing the radical-generating catalyst of the present invention with a radical-generating source. The mixture obtained by the mixing step may or may not further contain any substance other than the radical-generating catalyst of the present invention and the radical-generating source. For example, it is preferable to further mix a solvent in the mixing step from the viewpoint of reactivity, etc. In the present invention, the "solvent" may or may not dissolve the radical-generating catalyst, the radical-generating source, etc. For example, after the mixing step, the radical-generating catalyst of the present invention and the radical-generating source may each be in a dissolved state in the solvent, or may be in a dispersed or precipitated state in the solvent.

[0074] The radical production method of the present invention includes, for example, a radical production step in which radicals are produced by a reaction in the mixture obtained after the mixing step. As described above, the mixture may be, for example, in a solution state, a suspension state, a colloid state, or the like. From the viewpoint of reactivity, the mixture is preferably in a solution state or a colloid state. In the radical production step, for example, the mixture may simply be left at room temperature, or the mixture may be heated or irradiated with light, as necessary. The reaction temperature and reaction time in the radical production step are not particularly limited and can be appropriately set depending on, for example, the types of reactants (raw materials) and the target product. In the case of light irradiation, the wavelength of the irradiated light is not particularly limited and can be appropriately set depending on, for example, the absorption band of the reactants (raw materials). The reaction time and reaction temperature can also be adjusted, for example, by changing the concentrations of the radical-generating catalyst of the present invention and the radical-generating source in the mixture. For example, the reaction time can be shortened by increasing the concentration, but the present invention is not limited by this explanation.

[0075] The concentration of the radical-generating catalyst of the present invention is not particularly limited, but for example, the reaction mol / L relative to the solvent is not particularly limited and can be appropriately set depending on, for example, the types of reactants (raw materials) and the target product. The solvent is also not particularly limited, but may be, for example, water or an organic solvent. Examples of organic solvents include halogenated solvents such as methylene chloride, chloroform, and carbon tetrachloride, ketones such as acetone, nitrile solvents such as acetonitrile, alcohol solvents such as methanol and ethanol, acetic acid solvents, and sulfuric acid solvents. These solvents may be used alone or in combination of two or more. The acetic acid solvent and sulfuric acid solvent may be, for example, acetic acid or sulfuric acid dissolved in water, which functions as a solvent and also as a Lewis acid or Bronsted acid. The type of solvent may be selected depending on, for example, the solubility of the solute (e.g., the radical-generating catalyst of the present invention, the radical generating source, etc.).

[0076] In the method for producing radicals of the present invention, as described above, the reaction may be carried out by heating. However, radicals can also be produced by simply irradiating the reaction mixture with light without heating, or by simply leaving the reaction mixture at room temperature without heating or irradiating the reaction mixture with light. The definition of "room temperature" is not particularly limited, but is, for example, 5 to 35°C. Since heating is not required, the cost of heating using an electric furnace or the like is eliminated, and the cost of producing radicals can be significantly reduced. Furthermore, since heating is not required, unexpected runaway reactions due to radical chains and the accumulation of peroxides can be suppressed, for example, thereby significantly improving the safety of the reaction and further reducing costs. However, these explanations are merely examples and do not limit the present invention in any way.

[0077] The method for producing radicals of the present invention may further include, for example, a light irradiation step of irradiating the mixture obtained in the mixing step with light. As described above, radicals may be produced by a reaction induced by the light irradiation. The wavelength of the irradiated light is, for example, as described above. The light source is not particularly limited, but excitation can be easily achieved by using visible light contained in natural light such as sunlight. Furthermore, for example, light sources such as a xenon lamp, halogen lamp, fluorescent lamp, or mercury lamp may be used as appropriate instead of or in addition to the natural light. Furthermore, a filter that cuts off wavelengths other than the required wavelength may be used as appropriate, or may not be used.

[0078] In the radical production method of the present invention, the radical source may include at least one selected from the group consisting of halogen ions, hypohalite ions, halite ions, halogen ions, and perhalite ions. It is particularly preferable that the radical source include, for example, chlorite ions. The radical source may include, for example, an oxoacid or a salt thereof (e.g., a halogen oxoacid or a salt thereof). Examples of the oxoacid include boric acid, carbonic acid, orthocarbonic acid, carboxylic acid, silicic acid, nitrous acid, nitric acid, phosphorous acid, phosphoric acid, arsenic acid, sulfurous acid, sulfuric acid, sulfonic acid, sulfinic acid, chromic acid, dichromate, and permanganic acid. Halogen oxoacids include chlorine oxoacids such as hypochlorous acid, chlorous acid, chloric acid, and perchloric acid; bromine oxoacids such as hypobromous acid, bromous acid, bromic acid, and perbromic acid; and iodine oxoacids such as hypoiodous acid, iodous acid, iodic acid, and periodic acid.

[0079] The radical generating source may be appropriately selected depending on the application, taking into consideration the reactivity of the radical species, etc. For example, highly reactive hypochlorous acid and chlorous acid, which is slightly less reactive than hypochlorous acid and therefore easier to control the reaction, may be used depending on the purpose.

[0080] In the radical production method of the present invention, the radical generation source may include, for example, an electron donor-acceptor linked molecule. The electron donor-acceptor linked molecule is not particularly limited, but may, for example, have an electron donor moiety that is one or more electron-donating groups and an electron acceptor moiety that is one or more aromatic cations. In this case, the aromatic cation may be a monocyclic or fused ring, and the aromatic ring may or may not contain a heteroatom and may or may not have a substituent other than the electron-donating group. Furthermore, the aromatic ring that forms the aromatic cation is not particularly limited in the number of ring-constituting atoms, but may be, for example, a 5- to 26-membered ring.

[0081] The aromatic ring forming the aromatic cation is preferably at least one selected from the group consisting of a pyrrolinium ring, a pyridinium ring, a quinolinium ring, an isoquinolinium ring, an acridinium ring, a 3,4-benzoquinolinium ring, a 5,6-benzoquinolinium ring, a 6,7-benzoquinolinium ring, a 7,8-benzoquinolinium ring, a 3,4-benzoisoquinolinium ring, a 5,6-benzoisoquinolinium ring, a 6,7-benzoisoquinolinium ring, a 7,8-benzoisoquinolinium ring, and a ring in which at least one of the carbon atoms constituting the ring is replaced with a heteroatom. For example, if the aromatic cation is a macrocyclic (having a large number of π electrons) aromatic cation such as an acridinium ring, a benzoquinolinium ring, or a benzoisoquinolinium ring, for example, the absorption band shifts to the long wavelength side and has absorption in the visible light region, thereby enabling visible light excitation.

[0082] The electron-donating group is preferably at least one selected from the group consisting of a hydrogen atom, an alkyl group, and an aromatic ring. In this case, the aromatic ring may further have one or more substituents on the ring, and when there are multiple substituents, the substituents may be the same or different, and when there are multiple electron-donating groups, the substituents may be the same or different. In this case, the alkyl group in the electron-donating group is more preferably a linear or branched alkyl group having 1 to 6 carbon atoms. Furthermore, in the electron-donating group, the aromatic ring is more preferably at least one selected from the group consisting of a benzene ring, a naphthalene ring, an anthracene ring, a phenanthrene ring, a pyridine ring, a thiophene ring, and a pyrene ring. In the electron-donating group, the substituent on the aromatic ring is more preferably at least one selected from the group consisting of an alkyl group, an alkoxy group, a primary amine, a primary amine, a secondary amine, a carboxylic acid, and a carboxylic acid ester. In Ar, the substituent on the aromatic ring is more preferably at least one selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms, a primary to tertiary amine, a carboxylic acid, and a carboxylic acid ester. Regarding the substituent on the aromatic ring, "carboxylic acid" refers to a carboxyl group or a group having a carboxyl group attached to the terminal (e.g., a carboxyalkyl group), and "carboxylic acid ester" refers to a carboxylic acid ester group such as an alkoxycarbonyl group or a phenoxycarbonyl group, and an acyloxy group. The alkyl group in the carboxyalkyl group is preferably, for example, a linear or branched alkyl group having 1 to 6 carbon atoms, and the alkoxy group in the alkoxycarbonyl group is preferably, for example, a linear or branched alkoxy group having 1 to 6 carbon atoms.

[0083] The electron-donating group is more preferably at least one selected from the group consisting of phenyl, o-tolyl, m-tolyl, p-tolyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 2,3,4-trimethylphenyl, 2,3,5-trimethylphenyl, 2,3,6-trimethylphenyl, mesityl (2,4,6-trimethylphenyl), and 3,4,5-trimethylphenyl. Among these, mesityl is particularly preferred from the viewpoint of the lifetime of the electron transfer state (charge-separated state). While the reason why the mesityl group exhibits such excellent effects is unclear, it is thought that, for example, two methyl groups are present at the ortho positions, which facilitates perpendicular inter-relation between the benzene ring of the mesityl group and the aromatic ring of the aromatic cation, and that hyperconjugation within the mesityl group is reduced. However, this is only one example of a possible mechanism and does not limit the present invention in any way.

[0084] From the viewpoints of the lifetime of the electron transfer state (charge-separated state), oxidizing power, reducing power, etc., the electron donor-acceptor linked molecule is preferably at least one selected from the group consisting of a nitrogen-containing aromatic cation derivative represented by any one of the following formulas (A-1) to (A-8), a quinolinium ion derivative represented by the following formula (I), stereoisomers and tautomers thereof, and salts thereof.

[0085] [ka]

[0086] [ka]

[0087] In the formulas (A-1) to (A-8), R is a hydrogen atom or any substituent; Ar is the electron-donating group, and may be one or more, and when there are more than one, they may be the same or different; The nitrogen-containing aromatic ring forming the nitrogen-containing aromatic cation may or may not have one or more optional substituents other than R and Ar, In the formula (I), R 1 is a hydrogen atom or an optional substituent, Ar 1 ~Ar 3 are each a hydrogen atom or the above electron-donating group, and may be the same or different; Ar 1 ~Ar 3 At least one of the groups is the electron-donating group.

[0088] In the formulas (A-1) to (A-8), R is preferably a hydrogen atom, an alkyl group, a benzyl group, a carboxyalkyl group (an alkyl group having a carboxyl group attached to the terminal), an aminoalkyl group (an alkyl group having an amino group attached to the terminal), or a polyether chain. R is more preferably a hydrogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, a benzyl group, a linear or branched alkyl group having 1 to 6 carbon atoms and having a carboxyl group attached to the terminal, a linear or branched alkyl group having 1 to 6 carbon atoms and having an amino group attached to the terminal, or a polyethylene glycol (PEG) chain. A PEG chain is an example of the polyether chain, but the type of the polyether chain is not limited thereto and any polyether chain may be used. The degree of polymerization of the polyether chain in R is not particularly limited, but is, for example, 1 to 100, preferably 1 to 50, and more preferably 1 to 10. When the polyether chain is a PEG chain, the degree of polymerization is not particularly limited, but is, for example, 1 to 100, preferably 1 to 50, and more preferably 1 to 10.

[0089] The electron donor-acceptor linked molecule is more preferably at least one selected from the group consisting of 9-substituted acridinium ions represented by the following formula (A-9), and tautomers and stereoisomers thereof.

[0090] [ka]

[0091] In the formula (A-9), R and Ar are the same as in the formula (A-1).

[0092] Furthermore, it is particularly preferable that the electron donor-acceptor linked molecule is a 9-mesityl-10-methylacridinium ion represented by the following formula (A-10). This 9-mesityl-10-methylacridinium ion can generate a long-lived electron transfer state (charge-separated state) with high oxidizing and reducing power upon photoexcitation. Visible light, for example, can be used as the excitation light for the photoexcitation.

[0093] [ka]

[0094] Furthermore, examples of the 9-substituted acridinium ion represented by the formula (A-9) include the following (A-101) to (A-116) in addition to the above (A-10).

[0095] [Table A1]

[0096] In addition, in the quinolinium ion derivative represented by the formula (I), R 1 is preferably, for example, a hydrogen atom, an alkyl group, a benzyl group, a carboxyalkyl group (an alkyl group having a carboxyl group attached to the terminal), an aminoalkyl group (an alkyl group having an amino group attached to the terminal), or a polyether chain. 1 is more preferably, for example, a hydrogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, a benzyl group, a linear or branched alkyl group having 1 to 6 carbon atoms and a carboxyl group attached to the terminal, a linear or branched alkyl group having 1 to 6 carbon atoms and an amino group attached to the terminal, or a polyethylene glycol (PEG) chain. A PEG chain is an example of the polyether chain, but the type of the polyether chain is not limited thereto and any polyether chain may be used. 1In the above, the degree of polymerization of the polyether chain is not particularly limited, but is, for example, 1 to 100, preferably 1 to 50, and more preferably 1 to 10. When the polyether chain is a PEG chain, the degree of polymerization is not particularly limited, but is, for example, 1 to 100, preferably 1 to 50, and more preferably 1 to 10. In addition, Ar 1 ~Ar 3 are preferably, for example, a hydrogen atom, an alkyl group, or an aromatic ring, and the alkyl group is more preferably a linear or branched alkyl group having 1 to 6 carbon atoms. 1 ~Ar 3 In the above formula, the aromatic ring may further have one or more substituents on the ring, and when there are multiple substituents, the substituents may be the same or different.

[0097] In the formula (I), Ar 1 ~Ar 3 In the above, the aromatic ring is more preferably, for example, a benzene ring, a naphthalene ring, an anthracene ring, a phenanthrene ring, a pyridine ring, a thiophene ring, or a pyrene ring. 1 ~Ar 3 In the above, the substituent on the aromatic ring is more preferably an alkyl group, an alkoxy group, a primary or tertiary amine, a carboxylic acid, or a carboxylic acid ester, and even more preferably a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms, a primary or tertiary amine, a carboxylic acid, or a carboxylic acid ester. The secondary amine is not particularly limited, but is preferably, for example, an alkylamino group, more preferably a linear or branched alkylamino group having 1 to 6 carbon atoms. The tertiary amine is not particularly limited, but is preferably, for example, a dialkylamino group, more preferably a dialkylamino group having a linear or branched alkyl group having 1 to 6 carbon atoms.

[0098] In addition, Ar 1 ~Ar 3In the substituents on the aromatic ring, "carboxylic acid" refers to a carboxyl group or a group having a carboxyl group attached to the terminal (for example, a carboxyalkyl group), and "carboxylic acid ester" refers to a carboxylic acid ester group such as an alkoxycarbonyl group or a phenoxycarbonyl group, and an acyloxy group. The alkyl group in the carboxyalkyl group is preferably, for example, a linear or branched alkyl group having 1 to 6 carbon atoms, and the alkoxy group in the alkoxycarbonyl group is preferably, for example, a linear or branched alkoxy group having 1 to 6 carbon atoms.

[0099] Among the quinolinium ion derivatives represented by the formula (I), those particularly preferred from the viewpoints of a long life in a charge-separated state, high oxidizing power, high reducing power, etc. are, for example, quinolinium ion derivatives represented by any of the following formulas 1 to 5.

[0100] [ka]

[0101] In addition to the compounds 1 to 5, for example, compounds 6 to 36 shown in the following Tables 2 and 3 are particularly preferred. The structures of compounds 6 to 36 are shown in Tables 2 and 3, where R in formula (I) is a methyl group. 1 and Ar 1 ~Ar 3 Furthermore, by referring to the examples described below, those skilled in the art can easily produce and use these compounds 6 to 36 in accordance with compounds 1 to 5 without excessive trial and error or complicated and advanced experiments.

[0102] [Table A2]

[0103] [Table A3]

[0104] The electron donor-acceptor linked molecule may be a commercially available product or may be appropriately produced (synthesized). When produced, the production method is not particularly limited, and it can be produced appropriately by, for example, a known production method or by referring to a known production method. Specifically, for example, the production method described in Japanese Patent No. 5213142 may be used.

[0105] Furthermore, in the present invention, when a compound (e.g., the ammonium, the amino acid, the peptide, the phospholipid, the electron donor-acceptor linked molecule, etc.) has isomers such as tautomers or stereoisomers (e.g., geometric isomers, conformational isomers, and optical isomers), any of these isomers can be used in the present invention unless otherwise specified. Furthermore, when a compound (e.g., the electron donor-acceptor linked molecule, etc.) can form a salt, the salt can also be used in the present invention unless otherwise specified. The salt may be an acid addition salt or a base addition salt. Furthermore, the acid that forms the acid addition salt may be an inorganic acid or an organic acid, and the base that forms the base addition salt may be an inorganic base or an organic base. The inorganic acid is not particularly limited, but examples thereof include sulfuric acid, phosphoric acid, hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, hypofluorite acid, hypochlorous acid, hypobromous acid, hypoiodous acid, fluorite acid, chlorous acid, bromous acid, iodous acid, fluorine acid, chlorine acid, bromine acid, iodic acid, perfluorine acid, perchlorine acid, perbromine acid, and periodic acid. The organic acid is also not particularly limited, but examples thereof include p-toluenesulfonic acid, methanesulfonic acid, oxalic acid, p-bromobenzenesulfonic acid, carbonic acid, succinic acid, citric acid, benzoic acid, and acetic acid. The inorganic base is not particularly limited, but examples thereof include ammonium hydroxide, alkali metal hydroxides, alkaline earth metal hydroxides, carbonates, and bicarbonates, and more specifically, examples thereof include sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, calcium hydroxide, and calcium carbonate. The organic base is also not particularly limited, but examples thereof include ethanolamine, triethylamine, and tris(hydroxymethyl)aminomethane. The method for producing these salts is also not particularly limited, and they can be produced, for example, by adding the above-mentioned acid or base to the compound as appropriate using a known method.

[0106] Furthermore, in the present invention, unless otherwise specified, chain substituents (e.g., hydrocarbon groups such as alkyl groups and unsaturated aliphatic hydrocarbon groups) may be linear or branched, and the number of carbon atoms therein is not particularly limited and may be, for example, 1 to 40, 1 to 32, 1 to 24, 1 to 18, 1 to 12, 1 to 6, or 1 to 2 (2 or more in the case of unsaturated hydrocarbon groups). Furthermore, in the present invention, the number of ring members (the number of atoms constituting the ring) of cyclic groups (e.g., aryl groups, heteroaryl groups, etc.) is not particularly limited and may be, for example, 5 to 32, 5 to 24, 6 to 18, 6 to 12, or 6 to 10. Furthermore, when isomers exist in substituents, etc., any isomer may be used unless otherwise specified. For example, a simple "naphthyl group" may refer to either a 1-naphthyl group or a 2-naphthyl group.

[0107] [3. Method for producing oxidation reaction product] As described above, the method for producing an oxidation reaction product of the present invention includes the steps of: A method for producing an oxidation reaction product by oxidizing an oxidizable substance, comprising the steps of: a radical production step of producing the radical by the radical production method of the present invention; an oxidation reaction step in which the oxidized material is reacted with an oxidizing agent by the action of the radicals to generate the oxidation reaction product; The present invention is characterized by comprising:

[0108] The method for producing an oxidation reaction product of the present invention is not particularly limited. For example, in the mixing step, in addition to the radical-generating catalyst of the present invention and the radical-generating source, the oxidized material and the oxidizing agent may be further mixed. In this case, as described above, it is preferable to further mix a solvent. Then, in the radical production step, the oxidized material and the oxidizing agent may be reacted by the action of the generated radicals to produce the oxidation reaction product. That is, the oxidation reaction step may be performed simultaneously with the radical production step in the same reaction system in equilibrium with the radical production step. In this case, the concentrations of the oxidized material and the oxidizing agent are not particularly limited. For example, the reaction mol / L relative to the solvent is not particularly limited and can be set appropriately. Furthermore, for example, it is preferable to increase the concentration of the oxidized material as much as possible to increase the reaction rate, and it is preferable that the concentration of the oxidizing agent is not too high to facilitate the reaction. However, this explanation is merely an example and does not limit the present invention in any way.

[0109] In the method for producing an oxidation reaction product of the present invention, the radical may also serve as the oxidizing agent. For example, the radical generator may be an oxoacid, and the radical generated from the oxoacid may serve as the oxidizing agent. For example, the radical generator may be a chlorite ion ClO2 - and chlorite ion ClO2 - Radical ClO2 generated from · may be used as an oxidizing agent to oxidize the material to be oxidized to produce the oxidation reaction product.

[0110] Alternatively, the radical and the oxidizing agent may be different from each other. For example, the radical generator may be the electron donor-acceptor linked molecule, the oxidizing agent may be oxygen molecules O2, and the oxidized substance may be oxidized by the action of the radical of the electron donor-acceptor linked molecule and the oxygen molecules to produce the oxidation reaction product.

[0111] The substance to be oxidized is not particularly limited and may be, for example, an organic compound or an inorganic substance. For example, the substance to be oxidized may be triphenylphosphine PhP, and the oxidation reaction product may be triphenylphosphine oxide PhP=O. Alternatively, for example, the substance to be oxidized may be an olefin, and the oxidation reaction product may include at least one of an epoxide and a diol.

[0112] The material to be oxidized may be, for example, an aromatic compound (hereinafter, sometimes referred to as "raw aromatic compound"). In the present invention, the raw aromatic compound is not particularly limited. If an electron-donating group is bonded to the aromatic ring of the raw aromatic compound, it is preferable because, for example, the oxidation reaction (including oxidative substitution reaction) of the raw aromatic compound is likely to proceed. The electron-donating group may be one or more, and is preferably one with strong electron-donating properties. More specifically, the raw aromatic compound has an -OR group bonded to the aromatic ring. 100 , -NR 200 2, and Ar 100 It is more preferable that at least one substituent selected from the group consisting of R 100 is a hydrogen atom or an optional substituent, and R 100 If there are multiple R 100 may be the same or different. 200 is a hydrogen atom or an arbitrary substituent, and each R 200 may be the same or different. 100 is an aryl group, and Ar 100 If there are multiple Ar 100 may be the same or different.

[0113] The Ar 100 may be a group derived from any aromatic ring such as a benzene ring, a naphthalene ring, an anthracene ring, a phenanthrene ring, a pyridine ring, a thiophene ring, or a pyrene ring. The aromatic ring may further have one or more substituents on the ring, and when there are multiple substituents, the substituents may be the same or different. 100 is, for example, a phenyl group.

[0114] In addition, the R 100 is preferably at least one selected from the group consisting of a hydrogen atom, an alkyl group, an aryl group, and an acyl group. The alkyl group is preferably a linear or molecular alkyl group having 1 to 6 carbon atoms, and a methyl group is particularly preferred. The acyl group is preferably a linear or molecular acyl group having 1 to 6 carbon atoms. The aryl group is, for example, 100 and is, for example, a phenyl group.

[0115] In addition, the R 200 is preferably at least one selected from the group consisting of a hydrogen atom, an alkyl group, an aryl group, and an acyl group. The alkyl group is preferably a linear or molecular alkyl group having 1 to 6 carbon atoms, and a methyl group is particularly preferred. The acyl group is preferably a linear or molecular acyl group having 1 to 6 carbon atoms. The aryl group is, for example, 100 The —NR 200 As 2, an amino group substituted with an electron-donating substituent, such as a dimethylamino group or a diphenylamino group, is preferred because it has particularly high electron-donating properties.

[0116] The aromatic compound may have a substituent, such as an alkyl group, covalently bonded to the aromatic ring, and the substituent may be oxidized in the oxidation reaction product generation step. For example, the oxidizing agent may contain an oxygen atom, and the aromatic compound may contain a methylene group (-CH-) covalently bonded to the aromatic ring. In the oxidation reaction product generation step, the methylene group (-CH-) may be oxidized to a carbonyl group (-CO-). In this case, the atom or atomic group bonded to the methylene group and the carbonyl group is not particularly limited, and examples include a hydrogen atom, an alkyl group, and an aryl group. The alkyl group is preferably a linear or branched alkyl group having 1 to 6 carbon atoms. The alkyl group and aryl group may be further substituted with one or more substituents, and if there are multiple substituents, the substituents may be the same or different. For example, if hydrogen is bonded to the methylene group, it becomes a methyl group (-CH), which becomes a formyl group (-CHO) after oxidation. If a methyl group is bonded to the methylene group, it becomes an ethyl group (-CH2CH3), which becomes an acetyl group (-COCH3) after oxidation. If a phenyl group is bonded to the methylene group, it becomes a benzyl group (-CH2Ph), which becomes a benzoyl group (-COPh) after oxidation. Also, for example, the substituent covalently bonded to the aromatic ring (before oxidation) may be a formyl group (-CHO), which becomes a carboxy group (-COOH) after oxidation.

[0117] In the method for producing an oxidation reaction product of the present invention, the substance to be oxidized may be, for example, an olefin, such as an aromatic olefin or an aliphatic olefin. The olefin may be, for example, an olefin represented by the following chemical formula (A1). The oxidation reaction product of the olefin is not particularly limited, and may contain at least one of an epoxide and a diol, as shown in Scheme A below. In the following chemical formulas (A1), (A2), and (A3), R each represents a hydrogen atom or an arbitrary substituent, and each R may be the same or different. The arbitrary substituent may be, for example, an alkyl group, an unsaturated aliphatic hydrocarbon group, an aryl group, a heteroaryl group, a halogen atom, a hydroxy group (—OH), a mercapto group (—SH), or an alkylthio group (—SR, where R is an alkyl group), and may or may not be substituted with an additional substituent. The alkyl group is more preferably a linear or branched alkyl group having 1 to 6 carbon atoms. The olefin to be oxidized may be an olefin containing only one olefinic bond (carbon-carbon double bond), or may be an olefin containing a plurality of olefinic bonds (two or more).

[0118] [ka]

[0119] [ka]

[0120] The olefin may be, for example, an aromatic olefin, as described above. That is, for example, in the chemical formula (A1), at least one of R may be an aromatic ring (an aryl group or a heteroaryl group). Furthermore, the aromatic olefin may have, for example, an aromatic ring containing -OR as described above for the raw material aromatic compound. 100 , -NR 200 2, and Ar 100 At least one substituent selected from the group consisting of:

[0121] In the method for producing an olefin oxidation reaction product of the present invention, the olefin may be at least one selected from the group consisting of ethylene, propylene, styrene, and butadiene. Furthermore, the oxidation reaction product may be, for example, at least one of an epoxide and a diol, as described above. Examples are shown in Schemes A1 to A3 below. However, Schemes A1 to A3 below are merely illustrative, and the oxidation reactions of ethylene, propylene, and styrene in the present invention are not limited thereto.

[0122] [ka]

[0123] In the oxidation of an olefin (e.g., olefin (A1) in Scheme A), for example, it is possible to produce different oxidation reaction products by adjusting the concentration of at least one of the Lewis acid and Brönsted acid, the radical source, and the oxidizing agent. For example, when these concentrations are low relative to the oxidized compound, epoxides tend to be produced, while when these concentrations are high, diols tend to be produced, but this is not limiting. Alternatively, instead of the concentration, it is possible to produce different oxidation reaction products by adjusting the reactivity of the radical species generated from the radical source. For example, epoxides tend to be produced more easily with weakly reactive radical species, while diols tend to be produced more easily with highly reactive radical species, but this is not limiting. The applications of the oxidation reaction products are not particularly limited. For example, when the oxidized compound (raw aromatic compound) is styrene, styrene oxide can be used as an adhesive, and diols can be used as fragrances, etc. Since the epoxides and diols are each in demand for different applications, if they can be produced differently by controlling the reaction conditions, the present invention can be applied to even wider applications.

[0124] [4. Drugs] As described above, the agent of the present invention comprises a radical generating catalyst and a radical generating source, and the radical generating catalyst is the radical generating catalyst of the present invention. Other configurations and conditions of the agent of the present invention are not particularly limited. The ammonium may also serve as a substance having at least one of Lewis acidity and Bronsted acidity.

[0125] According to the present invention, it is possible to provide a drug that is highly safe and has a high bactericidal effect.

[0126] In addition, the agent of the present invention can be used, for example, as an agricultural and livestock agent. Hereinafter, the agent of the present invention that can be used as an agricultural and livestock agent may be referred to as the "agricultural and livestock agent of the present invention."

[0127] The agricultural and livestock agent of the present invention is highly safe and has a high bactericidal effect. Therefore, the agricultural and livestock agent of the present invention can be widely used, for example, for sterilization, deodorization, etc. in the agricultural and livestock industry. Furthermore, the agricultural and livestock agent of the present invention is, for example, less likely to cause corrosion, and is less likely to cause corrosion even when used on metals. Therefore, the agricultural and livestock agent of the present invention can be used, for example, on objects containing metals.

[0128] The agent of the present invention may be, for example, a radical generating catalyst that catalyzes the generation of radicals from at least one radical generating source selected from the group consisting of halous acid, halous acid ion, and halous acid salt.

[0129] In the agent of the present invention, for example, the Lewis acidity of the radical generating catalyst of the present invention is not particularly limited, but as described above, it is, for example, 0.4 eV or more, 0.5 eV or more, or 0.6 eV or more, and for example, 20 eV or less.

[0130] The pharmaceutical agent of the present invention may be, for example, liquid, solid, or semi-solid, and may be acidic or not, basic or not, or neutral or not.

[0131] The agent of the present invention is, for example, a radical-generating catalyst according to the present invention and at least one selected from the group consisting of a haloid acid, a haloid ion, and a haloid salt; the radical generating catalyst of the present invention is a radical generating catalyst that catalyzes the generation of radicals from at least one radical generating source selected from the group consisting of a halous acid, a halous acid ion, and a halous acid salt, and the Lewis acidity of the radical generating catalyst is 0.4 eV or more; It may also be a liquid drug characterized by being non-acidic.

[0132] In the agent of the present invention, the radical generating source may be appropriately selected, for example, depending on the application, taking into consideration the reactivity of the radical species, etc. For example, highly reactive hypochlorous acid and chlorous acid, which is slightly less reactive than hypochlorous acid and therefore easier to control the reaction, may be used depending on the purpose.

[0133] In the agent of the present invention, the content of the radical generating source (e.g., oxoacids, etc.) is not particularly limited, and may be, for example, 0.01 mass ppm or more, 0.05 mass ppm or more, 0.1 mass ppm or more, 1500 mass ppm or less, 1000 mass ppm or less, or 250 mass ppm or less. The radical generating source (e.g., oxoacids, etc.) is preferably mixed in the agent at 0.01 to 1500 mass ppm, more preferably 0.05 to 1000 mass ppm, and even more preferably 0.1 to 250 mass ppm. A lower concentration is preferred because lower concentrations are considered to be safer. However, if the concentration is too low, there is a risk that the bactericidal effect may not be obtained. From the viewpoint of bactericidal effect, the concentration of the radical generating source is not particularly limited, and the higher the concentration, the better.

[0134] In the agent of the present invention, the content of the radical-generating catalyst (e.g., ammonium, cationic surfactant, etc.) is not particularly limited, but may be, for example, 0.01 mass ppm or more, 0.05 mass ppm or more, 0.1 mass ppm or more, 1500 mass ppm or less, 1000 mass ppm or less, 500 mass ppm or less, or 250 mass ppm or less. The radical-generating catalyst (e.g., ammonium, cationic surfactant, etc.) is preferably mixed in the agent at 0.01 to 1500 mass ppm, more preferably 0.05 to 1000 mass ppm, more preferably 0.05 to 500 mass ppm, and even more preferably 0.1 to 250 mass ppm. Lower concentrations are considered to be safer, so lower concentrations are preferred. However, if the concentration is too low, there is a risk that the bactericidal effect may not be achieved. Furthermore, from the viewpoint of preventing the bactericidal effect from being lost due to micelle formation, the concentration of the radical-generating catalyst is preferably equal to or less than the micelle limit concentration.

[0135] In the pharmaceutical preparation of the present invention, the concentration ratio of the radical generating source and the radical generating catalyst (radical generating source / radical generating catalyst) in the pharmaceutical preparation is not particularly limited and can be set appropriately.

[0136] The pharmaceutical composition of the present invention may further contain other substances. Examples of such other substances include water, organic solvents, pH adjusters, buffers, etc., and one type may be used alone, or two or more types may be used in combination (the same applies below). The water is not particularly limited, but is preferably, for example, purified water, ion-exchanged water, or pure water.

[0137] The agent of the present invention preferably contains at least one of water and an organic solvent. In the present invention, the "solvent" may or may not dissolve the radical-generating catalyst of the present invention, the radical-generating source, etc. For example, after the mixing step, the radical-generating catalyst of the present invention and the radical-generating source may each be dissolved in the solvent, or may be dispersed or precipitated in the solvent. Furthermore, from the viewpoints of safety, cost, etc., it is preferable that the agent of the present invention uses water as a solvent for the radical-generating catalyst of the present invention and the radical-generating source. Examples of organic solvents include ketones such as acetone, nitrile solvents such as acetonitrile, and alcohol solvents such as ethanol. These solvents may be used alone or in combination of two or more. The type of solvent may be selected depending on, for example, the solubility of the solute (e.g., the radical-generating catalyst of the present invention, the radical-generating source, etc.).

[0138] The pH of the agent of the present invention is not particularly limited, and may be, for example, 4.0 or higher, 4.5 or higher, 5.0 or higher, 5.5 or higher, 6.0 or higher, 6.5 or higher, 7.0 or higher, or 7.5 or higher. The pH of the agent of the present invention may also be, for example, 11.5 or lower, 11.0 or lower, 10.5 or lower, 10.0 or lower, 9.5 or lower, 9.0 or lower, 8.5 or lower, 8.0 or lower, or 7.5 or lower.

[0139] The agent of the present invention can be produced, for example, by mixing the radical source, the radical-generating catalyst, and, if necessary, at least one of water and an organic solvent. For example, the agent of the present invention can be obtained as described in the Examples below, but is not limited thereto. Furthermore, as described above, the agent may contain other substances in addition to the radical source and the radical-generating catalyst.

[0140] The agricultural and livestock agent of the present invention preferably contains, for example, the water, but does not necessarily need to contain it. The amount of water mixed in the agricultural and livestock agent (water ratio) is not particularly limited. The water ratio may be, for example, the remainder of the other components. Furthermore, the agricultural and livestock agent may or may not further contain other substances, such as the pH adjuster or buffer.

[0141] The method of use of the agent of the present invention is not particularly limited, and can be used in the same manner as conventional disinfectants, for example. Specifically, the agent of the present invention can be sprayed or applied to an object. Specifically, for example, in the case of air deodorization, it can be used by spraying. For use in the oral cavity, it can be made into an aqueous solution so that it can be used for gargling or washing. For use in disinfecting bedsores, it can be applied to the affected area. For areas affected by spontaneously destructive cancer wounds or tinea fungus, it can be impregnated with absorbent cotton or gauze and applied to the affected area. For use in hand disinfection, it can be made into an aqueous solution so that it can be rubbed in. Medical instruments, etc. can be cleaned by spraying or immersing them in the aqueous solution. It can also be applied to areas around beds, tables, doorknobs, etc. for sterilization and prevention purposes.

[0142] (fungicide) The agent of the present invention can be used, for example, as a disinfectant. Although various disinfectants have been used in the past, their disinfecting effect is insufficient. Although some disinfectants can enhance their disinfecting effect by increasing their concentration, they have safety issues. The disinfectant containing the agent of the present invention has sufficient disinfecting effect even at a low concentration, and is highly safe.

[0143] (Hand sanitizer) The agent of the present invention can be used, for example, as a disinfectant for disinfecting hands and fingers for disinfecting hands, fingers, etc. A disinfectant for disinfecting hands containing the agent of the present invention has sufficient disinfecting effect even at a low concentration, and is highly safe.

[0144] (Deodorant) The agent of the present invention can be used, for example, as a deodorizer. Commonly used disinfectants, such as ethanol, lack deodorizing properties. Chlorine dioxide has deodorizing properties but is extremely unsafe. Other commercially available products claim to have bactericidal and deodorizing properties. For example, there are products that claim to have bactericidal and deodorizing properties by spraying the agent directly onto clothing, or indoors, in the toilet, or inside a car. Quaternary ammonium salts are typically used as the bactericidal component in these products. However, because commonly used quaternary ammonium salts do not incorporate a radical source (e.g., oxoacid), they often require high concentrations to achieve sufficient bactericidal effects and can cause stickiness after use. Furthermore, because quaternary ammonium salts lack deodorizing properties, they are typically mixed with a separate deodorizing component. Cyclodextrin is typically used as a deodorizing component, but it lacks the ability to decompose odor-causing components; it merely masks the odor-causing components and cannot eliminate the odor itself. In contrast, the deodorant containing the agent of the present invention has the above-mentioned mechanism of action, and therefore, for example, has a high bactericidal effect and can decompose substances that cause bad odors, thereby having a high deodorizing effect.

[0145] (Antibacterial agent for metals) The agent of the present invention can be used, for example, as an antibacterial agent for metals.An antibacterial agent containing the agent of the present invention is highly safe, so it can be sprayed or applied to metal products in the kitchen, for example.In addition, the antibacterial agent containing the agent of the present invention is less likely to cause corrosion, so it is less likely to corrode when used on metals.

[0146] (oral care agent) The agent of the present invention can be used, for example, as an oral care agent. Oral care agents containing the agent of the present invention are highly safe and therefore suitable for use in the oral cavity.

[0147] (Acne treatment drug) The agent of the present invention can be used, for example, as a therapeutic agent for acne. A therapeutic agent for acne containing the agent of the present invention is highly safe and can be applied to the face.

[0148] (Disinfectant for bedsores) The agent of the present invention can be used, for example, as a disinfectant for bedsores. Disinfectants for bedsores containing the agent of the present invention are highly safe and can be applied to the body.

[0149] (fungicide) The agent of the present invention can be used as a disinfectant for disinfecting areas affected by fungi such as tinea fungi.

[0150] (Disinfectant for water purification) The agent of the present invention can kill bacteria such as Legionella that occur in pool water and bath water. Moreover, it does not corrode metals or generate gases. Therefore, a disinfectant for water purification containing the agent of the present invention can be used safely.

[0151] Furthermore, the agent of the present invention can be used, for example, for the following purposes. As described above, the agent of the present invention is highly safe and has a high bactericidal effect. This also allows the agent of the present invention to exhibit, for example, a deodorizing effect. Therefore, the agent of the present invention is useful, for example, for improving QOL (quality of life).

[0152] As described above, the agent of the present invention is highly safe and can be used in humans. More specifically, it can be used for the following purposes, for example. (1) Prevention, treatment, and symptom relief of cystitis (2) Prevention, treatment, and symptom relief of candidiasis (including oral and vaginal cleansing) (2) Eye drops and eyewash (including for treating styes and other illnesses) (3) For ear and nose washing (otitis media, otitis externa, sinusitis, etc.) (4) Oral Cleaning and PMTC (Professional Mechanical Tooth Cleaning). This includes oral cleansing and PMTC for preventing aspiration pneumonia and improving the quality of life (QOL) of elderly or disabled people. (5) Peritoneal lavage (including treatment of peritonitis, peritoneal dissemination, etc.) (6) Intestinal cleansing (7) Disinfection and cleaning of skin tissues (8) Hand disinfection and washing (9) Disinfecting, cleaning, and wiping the affected area (including the wound) (10) Treatment of dermatitis such as atopic dermatitis (disinfection, cleaning, wiping of affected areas, etc.) (11) Disinfection and cleaning of affected areas due to bacterial infections such as eczema (paronychia), folliculitis, furuncles, etc.

[0153] Furthermore, the agent of the present invention can be used for general measures in the prevention and treatment of infectious diseases, for example. (1) Prevention of upper respiratory tract infections (including influenza, SARS, and MERS) (2) Prevention of food poisoning (norovirus, salmonella, etc.) (3) Vomit disposal (4) Inactivation of hepatitis B and C viruses. (5) Prevention, treatment, and symptom relief of ulcerative colitis. (6) Mold and fungus countermeasures (i.e., can be used for countermeasures other than bacteria and viruses). (7) Prevention, treatment, and symptom relief of stomatitis (side effects of molecular targeted drugs, etc.) (8) Pre- and post-operative care for surgery (including cancer surgery, etc.) (9) Care for cancer-affected areas (including oral cavity, mammograms, and open wounds)

[0154] Furthermore, the agent of the present invention can be used for the following purposes, taking advantage of its bactericidal action and high safety. (1) Cleaning dentures (2) Baby bottle sterilization (3) Disinfect (to prevent infection) and deodorize items around you that are touched by an unspecified number of people, such as desks and doorknobs. (4) Disinfecting and deodorizing public transportation such as trains, airplanes, and buses (5) Sterilization of the entire environment of schools, kindergartens, and daycare centers (including sterilization of desks, doors, shelves, switches, toys such as building blocks, etc. to prevent infection, etc.) (6) Sterilization of medical equipment (including cleaning and sterilization of the inside and pipes of artificial dialysis machines) (7) Wiping, cleaning, and washing diagnostic equipment such as X-rays, CT scans, and electrocardiograms (8) Sterilization of medical and surgical equipment (including scalpels, metals, resins, etc.)

[0155] Furthermore, the agent of the present invention can be used, for example, in the following applications by utilizing its proteolytic activity. (1) Contact lens solution (2) Eyeglass cleaning solution (3) Ultrasonic cleaner (4) Cleansing agent (5) Glass cleaning (including windshield)

[0156] Furthermore, the agent of the present invention can be used to eliminate odors such as those listed below by taking advantage of its deodorizing effect. (1) Bad breath (2) Body odor (3) Stool odor (4) Odors caused by chemical substances, gases, etc. (including general odors from factories such as chemical factories and food factories) (5) Garbage-related (6) Food waste, garbage collection points, garbage trucks, recycling centers, incineration plants (7) Sewerage pipes (8) Pipes, oil traps, and other trap equipment (9) Tobacco (10) Medical applications (including applications for improving patients' quality of life, and for eliminating odors caused by self-destructive wounds). (11) Operating Room (12) Hospital room (13) Environmental odors (feces odor, wastewater) from chicken coops, pig sheds, and cattle sheds (14) Meat Center (Slaughterhouse)

[0157] The agent of the present invention may be used ex vivo, for example. As described above, the agent of the present invention is highly safe, and therefore may be used in vivo, for example. The agent of the present invention may be used in vivo, for example, where the radical generating catalyst catalyzes radical generation from the radical generating source. The in vivo environment may be, for example, the human body, or may be the body of an animal other than a human.

[0158] The agent of the present invention may be used, for example, in the digestive tract. The agent of the present invention may be used, for example, in the digestive tract, where the radical-generating catalyst catalyzes radical generation from the radical-generating source. The digestive tract may be, for example, at least one selected from the group consisting of the oral cavity, pharynx, esophagus, stomach, duodenum, small intestine, and large intestine. The digestive tract may be, for example, the large intestine. The small intestine may be, for example, at least one selected from the group consisting of the duodenum, jejunum, and ileum. The large intestine may be, for example, at least one selected from the group consisting of the cecum, colon, and rectum. The agent of the present invention may be used, for example, for sterilization in the digestive tract, inducing changes in the intestinal flora, treating ulcerative colitis, or suppressing symptoms.

[0159] The agent of the present invention may be sprayed using, for example, a sprayer, a humidifier, etc. In this case, in addition to the bactericidal effect on the object to which it is sprayed, it is also possible to obtain a bactericidal effect and a deodorizing effect on the sprayer, humidifier, etc. Furthermore, the agent of the present invention is not limited to use by humans, but can also be used by animals other than humans. Specifically, it can be used, for example, for deodorizing animals and for preventing infectious diseases such as avian influenza and swine flu. Furthermore, examples of uses for animals other than humans include the same uses as those listed above for use by humans (including for use on the human body). Further examples of uses for animals other than humans include use as an agricultural and livestock agent, as described below.

[0160] As described above, the agricultural and livestock chemical agent of the present invention is highly safe and has a high bactericidal effect. Therefore, the agricultural and livestock chemical agent can be used, for example, as an agricultural chemical, a livestock chemical, etc. The agricultural chemical agent can be used, for example, as an agricultural fungicide, an agricultural antiviral agent, an agricultural deodorizer, an agricultural insecticide, an agricultural repellent, an agricultural soil improver, etc. Furthermore, the livestock chemical agent can be used, for example, as a livestock fungicide, an agricultural antiviral agent, an agricultural deodorizer, an agricultural insecticide, an agricultural repellent, an agricultural soil improver, etc. The agricultural and livestock chemical agent can be used, for example, for one purpose or for two or more purposes.

[0161] Examples of the agriculture include rice cultivation, field crops, etc. Examples of the field crops include vegetables such as cucumbers, tomatoes, leeks, Chinese cabbage, and soybeans, potatoes such as potatoes, flowers such as chrysanthemums, clematis, and bank roses, fruits such as strawberries, fertilizers, etc. Examples of the livestock industry include industrial animals such as cows, pigs, and chickens.

[0162] When the agricultural and livestock chemical agent of the present invention is used in rice cultivation, the agricultural and livestock chemical agent can be used, for example, as a fungicide, insecticide, repellent, soil conditioner, etc. Specifically, by using the agricultural and livestock chemical agent, for example, during soaking of rice seeds, the occurrence of slime can be prevented and the water exchange work can be reduced. Furthermore, by using the agricultural and livestock chemical agent, for example, during soaking, germination, and sowing, rice blast, sheath blight, rice koji disease, and blight rice disease can be prevented. By spraying the agricultural and livestock chemical agent, for example, on rice fields, rice plants can be protected from stink bugs, pests, and the like. By spraying the agricultural and livestock chemical agent, for example, during paddy field plowing, the soil can be improved.

[0163] When the agricultural and livestock agent of the present invention is used in field crops, the agricultural and livestock agent can be used, for example, as a fungicide, antiviral agent, soil conditioner, etc. Specifically, by spraying the agricultural and livestock agent on the leaves of, for example, cucumber, tomato, or strawberry, powdery mildew, mosaic disease, etc. can be prevented. By spraying the agricultural and livestock agent on, for example, tomato leaves, gray mold, downy mildew, etc. can be prevented. By spraying the agricultural and livestock agent on, for example, leeks, leaf rust, etc. can be prevented. By spraying the agricultural and livestock agent on, for example, Chinese cabbage leaves, clubroot disease, etc. can be prevented. By spraying the agricultural and livestock agent on a potato field after tillage using, for example, a tractor, and then plowing the field again, damage caused by continuous cropping can be prevented. For example, seed potatoes can be disinfected (sterilized) by immersing the seed potatoes in the agricultural and livestock agent. For example, by spraying the agricultural and livestock chemicals on potato leaves multiple times from the time the potatoes sprout until harvest, it is possible to prevent common scab and the like. For example, by spraying the agricultural and livestock chemicals on chrysanthemums, clematis, and bank roses, it is possible to prevent powdery mildew and the like.

[0164] When the agricultural and livestock agent of the present invention is used in the livestock industry, the agricultural and livestock agent can be used, for example, as a disinfectant or deodorizer. Specifically, by using the agricultural and livestock agent, for example, as a dipping agent for cattle, mastitis and the like can be prevented. By using the agricultural and livestock agent, for example, for cattle foot baths or by applying it to areas affected by hoof disease, hoof disease and the like can be prevented or treated. By spraying the agricultural and livestock agent on cattle with a sprayer or the like, respiratory diseases, foot-and-mouth disease, and the like can be prevented. By spraying the agricultural and livestock agent on cattle, pig, or chicken barns with a sprayer or the like, deodorization can be achieved. By using the agricultural and livestock agent on chicken eggs, for example, disinfection (sterilization) can be achieved.

[0165] The agricultural and livestock chemical agent of the present invention may be sprayed (atomized), applied, or scattered onto the target object, or the target object may be immersed in the agricultural and livestock chemical agent. Specifically, for example, in the case of air deodorization, it can be used by spraying. For areas affected by hoof disease, for example, absorbent cotton or gauze can be impregnated with the agent and applied to the affected area. When used for hand disinfection, for example, it can be made into an aqueous solution so that it can be rubbed in. Medical instruments, etc. can be cleaned by spraying or immersing them in the aqueous solution. When used on machinery such as automobiles, agricultural equipment, and forklifts used in the livestock barns, for example, the agricultural and livestock chemical agent can be sprayed on the machinery or washed with the agricultural and livestock chemical agent. When used as a deodorizing measure for industrial animals, it can be used by spraying with a sprayer or sprinkling with a sprinkler. Furthermore, chicken eggs can be sterilized by, for example, painting them.

[0166] <Fungicides for agricultural and livestock use> The agricultural and livestock fungicide of the present invention is characterized by containing the agricultural and livestock agent of the present invention. The agricultural and livestock agent of the present invention can be used, for example, as a fungicide. Various fungicides have been used in the past, but their fungicidal effect is insufficient. Some fungicides can increase their fungicidal effect by increasing the concentration, but there are safety issues. The agricultural and livestock fungicide containing the agricultural and livestock agent of the present invention has sufficient fungicidal effect even at a low concentration, and is highly safe.

[0167] <Disinfectant for hand disinfection for agricultural and livestock use> The disinfectant for hand disinfection for agricultural and livestock industries of the present invention is characterized by containing the agricultural and livestock agent of the present invention. The agricultural and livestock agent of the present invention can be used, for example, as a disinfectant for hand disinfection for agricultural and livestock industries for disinfecting hands, fingers, etc. The disinfectant for hand disinfection for agricultural and livestock industries containing the agricultural and livestock agent of the present invention has sufficient disinfecting effect even at a low concentration, and is highly safe.

[0168] <Deodorizer for agricultural and livestock use> The agricultural and livestock deodorizer of the present invention is characterized by containing the agricultural and livestock product agent of the present invention. The agricultural and livestock agent of the present invention can be used, for example, as an agricultural and livestock deodorizer. Quaternary ammonium salts are typically used as common disinfectant components. Quaternary ammonium salts often do not achieve sufficient disinfecting effect unless used at high concentrations, posing safety issues. Furthermore, since quaternary ammonium salts do not have a deodorizing effect, a separate deodorizing component is mixed in. Cyclodextrin is typically used as a deodorizing component, but cyclodextrin does not have the ability to decompose components that cause malodors; it merely masks the components that cause malodors and is unable to remove the malodors themselves. An agricultural and livestock deodorizer containing the agricultural and livestock agent of the present invention has, for example, a high disinfecting effect and can remove substances that cause malodors, resulting in a high deodorizing effect.

[0169] <Fungicide for agricultural and livestock use against fungi> The agricultural and livestock fungicide for fungi of the present invention is characterized by containing the agricultural and livestock agent of the present invention. The agricultural and livestock fungicide for fungi of the present invention can be used as a fungicide for disinfecting areas affected by fungi such as tinea fungi, for example.

[0170] <Water purification agent for agricultural and livestock use> The agricultural and livestock water purifying agent of the present invention is characterized by containing the agricultural and livestock chemical of the present invention. The agricultural and livestock water purifying agent of the present invention can, for example, sterilize bacteria such as Legionella that occur in water used for agricultural and livestock farming. Furthermore, the agricultural and livestock chemical of the present invention does not corrode metals or generate gases. Therefore, the agricultural and livestock water purifying agent containing the agricultural and livestock chemical of the present invention can be used safely. The agricultural and livestock water purifying agent of the present invention can be used, for example, to sterilize bacteria contained in water or improve water quality. Therefore, the agricultural and livestock water purifying agent of the present invention can also be referred to as, for example, a disinfectant for agricultural and livestock water or a water quality improver for agricultural and livestock water.

[0171] <How to use agricultural and livestock chemicals> The method for using the agricultural and livestock agent of the present invention is characterized by comprising a step of contacting an object with the agricultural and livestock agent of the present invention. The method for using the agricultural and livestock agent of the present invention can, for example, sterilize or deodorize the object. [Example]

[0172] Examples of the present invention will be described below, but the present invention is not limited to the following examples.

[0173] [Reference example 1] In this reference example, it was confirmed that the efficient dihydroxylation of styrene can be achieved by the use of scandium triflate and sodium chlorite. Specifically, the dihydroxylation of styrene can be achieved by the use of scandium triflate and chlorite ions (ClO2) at room temperature and atmospheric pressure. - The dihydroxylation of styrene with scandium triflate effectively produced 1-phenylethane-1,2-diol. Scandium triflate acts as a strong Lewis acid and reacts with the chlorite ion (ClO2 - ) to chlorine dioxide radical (ClO2 · ) and chlorine dioxide radicals (ClO2 · ) was confirmed to improve the reactivity.

[0174] The oxidation of olefins to 1,2-diols is an important industrial process in fine or specialty chemicals to produce precursors for various chemicals, such as resins, pharmaceuticals, dyes, pesticides, and fragrance compositions. Several methods for the oxidation of olefins to the corresponding epoxides and alcohols have been reported so far using inorganic metal oxo complexes and heavy metal oxides. High-valent Os VIII O4 is an effective and selective oxidizing reagent for converting olefins to 1,2-diols (References 1-8). However, the toxicity and sublimability of osmium compounds and their waste products pose serious problems. Sodium chlorite (NaClO2) is a non-toxic and inexpensive oxidizing reagent that produces chlorine dioxide radicals (ClO2). ·) has been used as a precursor for ClO2 (References 9-12 [same as Non-Patent Documents 1-4]). · is known to be a reactive and stable radical. However, ClO2 · is a yellow explosive gas at room temperature. ClO2 · can be prepared experimentally by the oxidation of NaClO2 with Cl2 and by the reaction of potassium chlorate (KClO3) with oxalic acid (References 13). These methods are limited by the toxicity of Cl2 and the - There is a risk that the explosiveness of ClO2 may become a problem. · Epoxidation of olefins using NaClO2 as a precursor to ClO2 has been attempted. · The oxidizing power of ClO2 is not strong enough to oxidize olefins to diols in the absence of acid, so 1,2-diol products were not obtained (References 14-17). · Activation of the Cl=O double bond of is key to selectively dihydroxylate olefins in one step.

[0175] In this example, scandium triflate [Sc(OTf)3] was used as the Lewis acid (Reference 18) and ClO2 · We report an efficient synthesis of styrene dihydroxylates at room temperature and pressure by activating styrene. The dihydroxylation mechanism was elucidated based on the detection of radical intermediates by EPR and UV-Vis absorption spectroscopy.

[0176] The reaction of styrene (2.0 mM) with NaClO (20 mM) in aqueous MeCN solution (MeCN / HO 1:1 v / v) at room temperature (25 °C) did not result in the dihydroxylation of styrene (see Figure 6). 1 The above reaction was carried out using CDCN / DO (1:1 v / v) as a solvent for H NMR spectroscopy. 1 The reaction was followed by HNMR, and the results are shown at 0.3 hours and 17 hours after the start of the reaction. 1The H NMR spectrum is shown. When the temperature was increased to 333 K, the formation of dihydroxylated products did not occur, and epoxidation occurred (Figure 7) (References 14, 19). Note that Figure 7 shows the results of the epoxidation of styrene (66 mM) and NaClO (200 mM) in CDCN / DO (4:1 v / v) at 60 °C (333 K) after 0 and 25 h. 1 The HNMR spectrum is shown. * indicates the peak derived from styrene oxide. In contrast, when CF3COOH (30 mM) was added as an additive as a Bronsted acid, no epoxide was formed after 17 hours of mixing. Instead, 1-phenylethane-1,2-diol (1) and 2-chloro-1-phenylethanol (2) were produced in 15% and 69% yields, respectively [Reaction Scheme (1)]. 1 The H NMR spectra were measured (Figure 8) (Reference 20). Figure 8 shows the results of the 1:1 v / v mixture of CDCN / DO containing styrene (2.0 mM), NaClO (20 mM), and Sc(OTf) (30 mM) at 25 °C for 0.6 and 17 hours. 1 The HNMR spectrum is shown. * and † indicate peaks due to 1-phenylethane-1,2-diol and 2-chloro-1-phenylethanol, respectively. When CF3COOH was replaced with the strong Lewis acid Sc(OTf)3 (30 mM), the yield of diol (1) increased significantly to 51% [see the table for reaction scheme (1) below] (Figure 19) (References 21). Figure 9 also shows the results of the diol (1) at 0.5 and 17 hours after mixing styrene (2.0 mM), NaClO2 (20 mM), and CF3COOH (30 mM) in CD3CN / DO (1:1 v / v). 1 The HNMR spectrum is shown. * and † indicate peaks due to 1-phenylethane-1,2-diol and 2-chloro-1-phenylethanol, respectively.

number

[0177] UV-Vis absorption spectroscopy was employed to clarify the reaction mechanism and detect reactive intermediates. As shown in Figure 1, NaClO2 exhibited an absorption band at 260 nm in aqueous solution. This absorption band disappeared upon addition of Sc(OTf)3 (10 mM), and a new absorption band at 358 nm was observed. This absorption band was associated with ClO2. · The absorption band was identified (assigned) based on the above (References 22, 23). Similar changes in the absorption spectrum were observed in the presence of CF3COOH (Reference 24). The time course of the appearance of the absorption band at 358 nm is shown in Figure 1. Figure 1 shows the UV+visible absorption spectra of NaClO2 (5.0 mM) collected at 0, 4, and 16 hours after mixing with Sc(OTf)3 (10 mM) in aqueous solution at 298 K. In this figure, the horizontal axis represents wavelength (nm) and the vertical axis represents absorbance. Figure 2(a) also shows the Sc(OTf)3 band obtained from the same reaction as in Figure 1 (the reaction of Sc(OTf)3 (10 mM) with NaClO2 (5.0 mM) in aqueous solution (0.20 M acetate buffer, pH 2.9) at 298 K). 3+ (ClO2 · 2(a) and 2(b) show the time profile of UV-Vis absorption at 358 nm of the formation of ClO2 with Sc(OTf)3. In this figure, the horizontal axis is time (seconds) and the vertical axis is absorbance at 358 nm. Figure 2(b) is a quadratic plot of the measurement results in Figure 2(a). The time profile (Figure 2(a)) matches well with the quadratic plot (Figure 2(b)). Thus, the formation of ClO2 with Sc(OTf)3 · The formation of two molecules of ClO2 - is involved in the rate-determining step (see below). The bimolecular rate constant is 0.16 M -1 s -1 It was determined that.

[0178] In the absence of substrate, ClO2 was produced from NaClO2 using Sc(OTf)3 in MeCN at 298 K. · No decay of the absorbance at 358 nm due to the addition of styrene was observed. Figure 3(a) shows the Sc(II) in MeCN / HO (1:1 v / v) solution at 298 K in the presence of styrene (30-90 mM). 3+ (ClO2 ·) consumption. In this figure, the horizontal axis is time (seconds) and the vertical axis is ClO2 · (b) Plot of pseudo-first-order rate constant versus styrene concentration. In the presence of excess styrene, the decay rate followed pseudo-first-order (Fig. 3(a)). The observed pseudo-first-order rate constant for dihydroxyl increase (k obs ) increased linearly with increasing styrene concentration (Fig. 3(b)). · and the bimolecular rate constant for styrene consumption is 1.9 x 10 -2 M -1 s -1 (References 25). EPR (electron paramagnetic resonance) measurements were carried out to clarify the radical structure. · was prepared by refluxing a MeCN solution containing NaClO2 at 353 K for 1 h. After cooling to 298 K, the EPR spectrum showed a characteristic isotropic signal at g = 2.0151 (±0.0002) along with four hyperfine lines originating from the unpaired electrons of the Cl nuclei ( 35 Cl and 37 In Cl, I = 3 / 2, and they have similar magnetic moments of 0.821 and 0.683, respectively (Figure 4(a)) (Ref. 26). The G values ​​changed significantly with the addition of CF3COOH (g = 2.0106) and Sc(OTf)3 (g = 2.0103) (Figures 4(b) and 4(c)). · The hyperfine coupling constant of (a(Cl) = 16.26 G) was reduced in the presence of CF3COOH (15.78 G) and Sc(OTf)3 (15.56 G) (References 27). This is due to the presence of protons and Sc 3+ However, H is a strong intermediate in the dihydroxylation of styrene. + ClO2 · and Sc 3+ ClO2 · To form ClO2 · It has been shown that it binds to (References 28).

[0179] As shown in Figure 5, ClO2 · , H + ClO2 · and Sc 3+ ClO2 · Density functional theory (DFT) calculations were performed to predict the reaction mechanism for dihydroxylation. Geometry optimization was performed at the DFT CAM-B3LYP / 6-311+G(d,p) level of theoretical calculations. Figure 5 shows the bond lengths (Å) of the DFT-optimized structures calculated at the CAM-B3LYP / 6-311+G(d,p) level of theoretical calculations. (a) shows ClO2 · , (b) is H + ClO2 · ,(c) is Sc 3+ ClO2 · ClO2 · The bond length of the Cl-O double bond in was calculated to be 1.502 Å (Figure 5(a)). + ClO2 · In this case, the bond length of the Cl-O double bond was calculated to be 1.643 Å (Fig. 5(b)). · Compared with Sc 3+ ClO2 · The bond strength is also significantly weakened (Cl-O: 1.818 Å). The cleavage of the Cl-O bond indicates the existence of ClO as a strong oxidant in the presence of substrate. · It may be advantageous to generate H. + ClO2 · and (b) Sc. 3+ ClO2 · This figure shows the spin distribution of the above by theoretical calculation at the CAM-B3LYP / 6-311+G(d,p) level.

[0180] Based on the above results, ClO2 · The mechanism of the dihydroxylation of styrene by NaClO2 is shown in Reaction Equations (2)-(5) and Scheme 1. The disproportionation reaction of NaClO2 is + or Sc 3+ occurs in the presence of ClO - and ClO3 - This forms [Reaction Scheme (2)] (References 29). - is ClO2 -and protons to produce Cl2O2 [Reaction (3)]. Next, Cl2O2 reacts with ClO2 - is reduced by the reactive species ClO2 · [Equation (4)]. The overall stoichiometry is given by Equation (5). ClO2 · is H + and Sc 3+ It is activated by combining with acids such as H + In the case of H, based on DFT calculations (see above), no Cl-O bond cleavage occurs. + The oxidation of styrene by ClO2 · In contrast, Sc 3+ The dihydroxylation of styrene by Sc is shown in Scheme 1. 3+ ClO2 · Homolytic Sc ​​complex 3+ ClO produced by Cl-O bond cleavage · and Sc 3+ O · The scandium complex then reacts with the diol to form the final product, Sc. 3+ ClO · It is hydrolyzed to give Sc (Scheme 1). 3+ ClO · is a large excess of ClO2 - Oxidation by Sc 3+ ClO2 · can be formed and reused. - is also reacted with ClO2 as shown in reaction (2). - It can be regenerated by Sc 3+ ClO2 · ClO formed by cleavage of the Cl-O bond · Addition of β-carbon to styrene gave two isomers. When β-carbon-ClO bond formation occurred, the chlorinated compound was obtained as the final minor product, as shown in Scheme 1.

[0181]

number

[0182] [ka]

[0183] As shown above, according to this reference example, ClO2 · Sc 3+ It has been shown that styrene is an effective dihydroxylating reagent as a Lewis acid in the presence of . The present invention provides a unique route to dihydroxylate olefins without the generation of hazardous wastes such as heavy metals.

[0184] [References, etc.] 1 M. Schroeder, Chem. Rev., 1980, 80, 187-213. 2 (a) EN Jacobsen, I. Marko, WS Mungall, G. Schroeder and KBSharpless, J. Am. Chem. Soc., 1988, 110, 1968-1970; (b) SGHentges and KB Sharpless, J. Am. Chem. Soc., 1980, 102, 4263-4265. 3 W. Yu, Y. Mei, Y. Kang, Z. Hua and Z. Jin, Org. Lett., 2004, 6,3217-3219. 4 (a) AJ DelMonte, J. Haller, KN Houk, KB Sharpless, DASingleton, T. Strassner, and AA Thomas, J. Am. Chem. Soc., 1997,119, 9907-9908. (b) JSM Wai, I. Marko, JS Svendsen, MGFinn, EN Jacobsen and KB Sharpless, J. Am. Chem. Soc., 1989,111, 1123-1125. 5 (a) S. Kobayashi, M. Endo and S. Nagayama, J. Am. Chem. Soc.,1999, 121, 11229-11230; (b) S. Kobayashi, T. Ishida and R. Akiyama,Org. Lett., 2001, 3, 2649-2652. 6 H. C. Kolb, P. G. Andersson and K. B. Sharpless, J. Am. Chem. Soc.,1994, 116, 1278-1291. 7 E. J. Corey and M. C. Noe, J. Am. Chem. Soc., 1996, 118, 11038-11053. 8 S. Y. Jonsson, K. Faernegrdh and J.-E. Baeckvall, J. Am. Chem. Soc.,2001,123, 1365-1371. 9 H. Dodgen and H. Taube, J. Am. Chem. Soc., 1949, 71, 2501-2504. 10 J. K. Leigh, J. Rajput, and D. E. Richardson, Inorg. Chem., 2014, 53,6715-6727. 11 C. L. Latshaw, Tappi, 1994, 163-166. 12 (a) J. J. Leddy, in Riegel’s Handbook of Industrial Chemistry, 8 th edn. Ed., J. A. Kent, Van Nostrand Reinhold Co. Inc, New York, 1983, pp. 212-235; (b) I. Fabian, Coord. Chem. Rev., 2001, 216-217, 449-472. 13 M. J. Masschelen, J. Am. Works Assoc., 1984, 76, 70-76. 14 X.-L. Geng, Z. Wang, X.-Q. Li, and C. Zhang J. Org. Chem., 2005, 70, 9610-9613 15 A. Jangam and DE Richardson, Tetrahedron Lett., 2010, 51, 6481-6484. 16 JJ Kolar and BO Lindgren, Acta Chem. Scand. B, 1982, 36, 599-605. 17 BO Lindgren, T. Nilsson, Acta Chem. Scand. B, 1974, 28, 847-852. 18 (a) S. Fukuzumi and K. Ohkubo, J. Am. Chem. Soc., 2002, 124, 10270-10271; (b) S. Fukuzumi and K. Ohkubo, Chem.-Eur. J., 2000, 6, 4532-4535. 19 The epoxidation of styrene (66 mM) with NaClO2 (200 mM) was investigated in a MeCN / H2O (4:1 v / v) mixed solution at 333 K (References 14). The yield of styrene oxide was 44%, and the conversion of styrene was 61%. 20 EV Bakhmutova-Albert, DW Margerum, JG Auer and BM Applegate, Inorg. Chem., 2008, 47, 2205-2211. twenty one 1 No intermediate styrene epoxide was observed during the reaction with CF3COOH or Sc(OTf)3, as confirmed by H NMR. 22 C. Rav-Acha, E. Choushen (Goldstein) and S. Sarel, Helv. Chim. Acta, 1986, 69, 1728-1733. 23 ClO2 ·It is produced in aqueous solution from acetic anhydride and NaClO2 (References 22). · is the protonated form (H + ClO2 · ) is possible. 24 W. Masschelein, Ind. Eng. Chem. Prod. Res. Devel., 1967, 6, 137-142. 25 This figure is based on ClO2 · Conversion of styrene to epoxide by (1.17 × 10 -2 M -1 s -1 ) (References 10) is slightly larger. 26 (a) T. Ozawa and T. Kwan, Chem. Pharm. Bull., 1983, 31, 2864-2867; (b) T. Ozawa, T. Trends Org. Chem., 1991, 2, 51-58. 27 Sc 3+ ClO2 · and H+ClO2 · The calculated spin distribution of Sc is shown in Figure 5. According to this, Sc and H nuclei do not show spin density, which means that the EPR spectrum does not show hyperfine splitting due to Sc (I = 7 / 2) or H (I = 1 / 2). 28 Sc 3+ For the bond between and the oxo group of a metal oxo complex, see below: (b) H. Yoon, Y.-M. Lee, X. Wu, K.-B. Cho, YN Pushkar, W. Nam and S. Fukuzumi, J. Am. Chem. Soc., 2013, 135, 9186-9194; (c) S. Fukuzumi, K. Ohkubo, Y.-M. Lee and W. Nam, Chem.-Eur. J., 2015, 21, 17548-17559. 29 Sc 3+ For the disproportionation of neutral radicals by , see I. Nakanishi, T. Kawashima, K. Ohkubo, T. Waki, Y. Uto, T. Kamada, T. Ozawa, K. Matsumoto and S. Fukuzumi, S. Chem. Commun., 2014, 50, 814-816.

[0185] [Example 1] In this example, we investigated the activation of oxygen reduction reactions using benzethonium chloride. Lewis acids have been widely researched and developed in various organic synthesis reactions. Much of this research has focused on using metal ions or metal complexes as Lewis acid sites and designing the surrounding ligands. In this example, we used benzethonium chloride as an ammonium derivative with strong Lewis acidity, and confirmed that it is widely useful in oxygenation reactions of aromatic organic compounds using sodium chlorite.

[0186] In acetonitrile, the cobalt(II) tetraphenylporphyrin complex Co(II)TPP (TPP = 5,10,15,20-tetraphenylporphyrin) (E ox =0.35V vs SCE) and molecular oxygen (Ered = -0.86 V vs SCE), no electron transfer occurs between the two solutions. However, this oxygen-saturated solution ([CoTPP] = 9.0 × 10 -6 M, [O2] = 13 mM, benzethonium chloride (Bzn + ) is added ([Bzn + Cl - At a concentration of 0.01% (=30 mM), the absorption band at 411 nm attributable to Co(II)TPP was attenuated, and an increase in the absorption band at 433 nm characteristic of Co(III)TPP+ was observed, while the absorption band had an isosbestic point (Figure 11(a)). Figure 11(a) is a graph showing the time-dependent change in the UV+visible absorption spectrum of the solution, with the horizontal axis representing wavelength (nm) and the vertical axis representing absorbance. This indicates that the electron transfer reaction from Co(II)TPP to molecular oxygen proceeded, resulting in the formation of Co(III)TPP. + The time constants for the decay of the 411 nm absorption band and the increase of the 433 nm absorption band are almost identical, and a pseudo-first-order curve fit gave a rate constant of 9.3 × 10 -5 s -1 (Fig. 2(b)). In the graph of Fig. 11(b), the horizontal axis is time and the vertical axis is absorbance. This rate constant is determined by the oxygen concentration and Bzn + The plot shows a linear dependence on the concentration, and the catalytic transfer rate constant (k cat ) to 0.24M -2 s -1 Previous studies (Ohkubo, K.; Fukuzumi, S. Chem. Eur. J., 2000, 6, 4532) have shown that the electron transfer reaction from Co(II)TPP to molecular oxygen proceeds efficiently in the presence of a Lewis acid such as a metal ion. + In the case of Bzn obtained in this example, the reaction is also thought to have proceeded under the influence of a Lewis acid catalyst. + The catalytic rate constant (0.24M -2 s -1 ) is slightly lower than that of lithium perchlorate (0.36) and strontium perchlorate (0.10M -2 s -1 ) and barium perchlorate (0.051M-2 s -1 ) was larger than the above results. + is considered to have a relatively strong Lewis acidity. Using this catalytic rate constant and a method described in the literature, the ΔE value, an index of Lewis acidity, was determined to be 0.53 eV. In fact, there have been reports in the past that ammonium salts function as Lewis acids, and this value was greater than that of ammonium hexafluorophosphate (NH4PF6) (0.32 eV) (References 33), confirming that this ammonium salt exhibits a strong Lewis acidity among ammonium salts. In addition, the graph in Figure 21 shows the ΔE value of benzethonium chloride [Bzn + Cl - ] and the Lewis acidity of various metal complexes. In the figure, the horizontal axis is the ΔE value (eV), and the vertical axis is the logarithm of the rate constant (log(k cat ,M -2 s -1 )).

[0187] Bzn from density functional calculations (B3LYP / 6-31G(d) level) + The structure of Bzn was optimized. The structure is shown in Figure 12. As shown in the figure, the Mulliken charge and LUMO orbital are localized near the ammonium nitrogen. + is expected to exhibit Lewis acidity.

[0188] [Reference example 2] In this example, the accelerating effect of a Lewis acid on the disproportionation reaction of NaClO2 was confirmed.

[0189] As confirmed in Reference Example 1, sodium chlorite (NaClO2) is very stable in a neutral aqueous solution / acetonitrile mixture, and no decomposition is observed. When Sc(OTf)3 (40 mM) is added to this 20 mM solution, the absorption band of NaClO2 is attenuated, and ClO2 radicals (ClO2 ·) was observed (Figure 13). In this figure, the horizontal axis represents wavelength (nm) and the vertical axis represents absorbance. As confirmed in Reference Example 1 (Figure 1), this increase in the absorption band could be observed as a change over time when the concentration of Sc(OTf)3 was reduced. Similar studies were also conducted with magnesium ions and lithium ions, which have lower Lewis acidity than scandium ions, and the reaction rate constants for each were determined. Lewis acids have been known to catalyze various disproportionation reactions, and in this reaction, a similar mechanism was used to convert ClO according to reaction equation (2) in Reference Example 1. 2- ClO - and ClO3 - It is thought that the ClO - ClO2 exists in large excess - It is thought that this reacts with Cl2O2 in the presence of an acid to give Cl2O2 (Reaction Scheme (3) in Reference Example 1). - It is thought that this reacts with ClO2 to give ClO2 radicals, which are active radical species (reaction formula (4) in Reference Example 1).

[0190] [Example 2] In this example, the generation of ClO2 radicals and the promotion of oxidation reactions using benzethonium chloride were confirmed.

[0191] First, because the ClO2 radical is thought to exhibit strong oxygenation reaction activity, 10-methyl-9,10-dihydroacridine (AcrH2) (1.4 mM) and sodium chlorite (NaClO2) (2.8 mM) were added to a deoxygenated acetonitrile / water (1:1 v / v) mixed solution. In this case, the oxygenation reaction of AcrH2 hardly progressed (Figure 14). Graphs in Figures 14(a) to 14(c) show the time course of the reaction. In Figure 14(a), the horizontal axis represents wavelength (nm) and the vertical axis represents absorbance. Figure 14(b) is a graph showing the time course of absorbance at a wavelength of 358 nm, where the horizontal axis represents time (seconds) and the vertical axis represents absorbance. Figure 14(c) is a graph showing the time course of absorbance at a wavelength of 387 nm, where the horizontal axis represents time (seconds) and the vertical axis represents absorbance.

[0192] Next, the same mixed solution as in Figure 14 was prepared, and then Bzn + When 10-methylacridone (λ) was added, the oxygenation reaction of AcrH2 to 10-methylacridone proceeded (Figure 15). The graphs in Figures 15(a) and (b) show the time course of the reaction. In Figure 15(a), the horizontal axis is wavelength (nm) and the vertical axis is absorbance. Figure 15(b) is a graph showing the time course of absorbance at a wavelength of 387 nm, where the horizontal axis is time (seconds) and the vertical axis is absorbance. As shown in Figures 15(a) and (b), the oxygenation reaction of 10-methylacridone (λ) max The increase in absorption due to the absorption peak at 382 nm over time confirmed that the oxygenation (oxidation) reaction of AcrH2 to 10-methylacridone had progressed.

[0193] Furthermore, when scandium trifluoromethanesulfonate (Sc(OTf)3, 3.0 mM) was further added to the same mixed solution as in Figure 15, the oxygenation reaction from AcrH2 to 10-methylacridone proceeded (Figure 16). The graphs in Figures 16(a) and (b) show the time course of the reaction. In Figure 16(a), the horizontal axis represents wavelength (nm) and the vertical axis represents absorbance. Figure 16(b) is a graph showing the time course of absorbance at a wavelength of 430 nm, where the horizontal axis represents time (seconds) and the vertical axis represents absorbance. As shown in Figures 16(a) and (b), the absorption derived from 10-methylacridone increased over time, confirming that the oxygenation (oxidation) reaction from AcrH2 to 10-methylacridone had proceeded. This oxygenation reaction is thought to proceed via the chain reaction mechanism shown in Figure 17. That is, here, ClO2 · is thought to give acridone by simultaneously abstracting hydrogen from 10-methylacridone and adding oxygen. On the other hand, the product after oxygen addition, ClO · is ClO2 - undergoes an electron transfer reaction with ClO - and ClO2 · It is thought that this gives rise to regeneration.

[0194] [Reference example 3] In this Reference Example, the oxygenation reaction of a substrate with NaClO2 using a Lewis acid was used to convert triphenylphosphine to triphenylphosphine oxide, and its usefulness was confirmed. More specifically, the oxygenation reaction of triphenylphosphine to triphenylphosphine oxide using NaClO2 was carried out in the presence and absence of scandium triflate Sc(OTf)3, a Lewis acid, and it was confirmed that the Lewis acid promoted the reaction.

[0195] First, under the following conditions, a reaction was carried out in the presence or absence of Sc(OTf)3 at room temperature and pressure (without light irradiation), and the reaction was followed by UV-visible absorption spectroscopy. The UV-visible absorption spectrum in Figure 22(a) shows the process of triphenylphosphine being converted to triphenylphosphine oxide over time. In the figure, the horizontal axis is wavelength (nm) and the vertical axis is absorbance. The graph in Figure 22(b) shows the change in the wavelength (nm) of Sc(OTf)3 (Sc 3+ The graph shows the time course of triphenylphosphine (Ph3P) concentration in the presence and absence of Sc. The horizontal axis is time (seconds) and the vertical axis is triphenylphosphine (Ph3P) concentration (mM). As shown in the figure, the reaction rate constant k calculated from this curve is 3+ In the absence of -4 S -1 whereas Sc 3+ 1.7 × 10 in the presence of -3 S -1 Since the number of cases increased, Sc 3+ It was confirmed that the Lewis acid promoted the reaction. [Ph3P]=0.4mM [NaClO2] = 0.4 mM Sc(OTf)3 = 0 or 10 mM 0.12M acetate buffer pH 5.3 MeCN / HO (4:6)

[0196] Furthermore, when triphenylphosphine and NaClO2 (4.0 mM) were mixed in deoxygenated acetonitrile MeCN / H2O (0.9 ml / 0.1 ml), no reaction proceeded at all. Addition of scandium triflate Sc(OTf)3 (30 mM) to this mixture efficiently produced an oxygenated product. The reaction was carried out at 25°C for 15 minutes, with the initial triphenylphosphine concentration varied between 1.0 mM, 2.0 mM, 4.0 mM, and 8.0 mM. The reaction was monitored by observing changes in the UV-visible absorption spectrum (Figure 18(a)). In Figure 18(a), the horizontal axis represents wavelength (nm) and the vertical axis represents absorbance. This indicates that the scandium ion Sc 3+ It is believed that ClO2 radicals, which are active radical species, are generated by this reaction, and Ph3P is oxygenated to Ph3P=O. The stoichiometry is as shown in reaction equation (6) below, and it was confirmed that the reaction proceeds almost quantitatively (Figure 18(b)). In Figure 18(b), the horizontal axis represents the initial concentration of Ph3P, and the vertical axis represents the concentration of the generated Ph3P=O. 2Ph3P+NaClO2--> 2Ph3P=O+NaCl (6)

[0197] [Reference example 4] In this example, 9-mesityl-10-methylacridinium (Acr + -Mes) perchlorate (Acr + -MesClO4 - The starting aromatic compound (benzaldehyde) was oxidized in the presence of Bzn and oxygen to obtain the oxidation product (benzoic acid) (Figure 20). + Cl - The experiments were carried out in the presence and absence of

[0198] As the reaction solvent, 0.6 mL of CD3CN saturated with oxygen gas was used. + -MesClO4 - 1 mM, benzaldehyde (PhCHO) 5 mM, Bzn + Cl -The reaction was irradiated with or without light of 390 nm wavelength from a xenon lamp. 1 The reaction was followed by HNMR. The results are shown in the table in Figure 20. In the table, "x" indicates that no reagent was added or that light was not irradiated. "○" indicates that light was irradiated. "Conversion" is the conversion rate of the raw material aromatic compound (benzaldehyde), "yield" is the yield of benzoic acid, and "time" is the reaction time. As shown in Figure 20, Bzn + Cl - When no Bzn was added, the yield of benzoic acid was trace. + Cl - When Acr was added, the yield of benzoic acid was 60% and the conversion rate of benzaldehyde was 63%. + -Mes is a Lewis acid (Bzn + Cl - ), but is less reactive in the absence of Lewis acids (Bzn + Cl - ) in the presence of Acr + This is thought to indicate that radical generation from -Mes is promoted, making it a powerful reactant.

[0199] [Reference example 5] In this reference example, the oxidation reaction product of cobalt tetraphenylporphyrin was produced by the measurement method described above in "Method for Measuring Lewis Acidity" using various ammoniums as radical generating catalysts and oxygen molecules as radical generating sources (which also serve as oxidizing agents). That is, cobalt tetraphenylporphyrin, saturated O2, and the object to be measured for Lewis acidity (e.g., a cation of a metal, etc., which is represented by M in the following chemical reaction formula (1a)) were used. n+ The change in the ultraviolet-visible absorption spectrum of acetonitrile (MeCN) containing CoTPP (represented by + It was confirmed that this was obtained.

[0200]

number

[0201] The oxidation reaction was carried out using each ammonium shown in the table below as a radical-generating catalyst. cat ,M -2 s -1 The numbers represented by " are the reaction rate constants of CoTPP and oxygen in the presence of a Lewis acid, which are indicative of the Lewis acidity of each ammonium. The numbers represented by "LUMO, eV" are the LUMO energy levels. Additionally, "benzethonium chloride" represents benzethonium chloride, "benzalkonium chloride" represents benzalkonium chloride, "tetramethylammonium hexafluorophosphate" represents tetramethylammonium hexafluorophosphate, "tetrabutylammonium hexafluorophosphate" represents tetrabutylammonium hexafluorophosphate, and "ammonium hexafluorophosphate" represents ammonium hexafluorophosphate.

[0202] [Table tpp]

[0203] [Example of drug] Next, specific examples of the drug of the present invention will be described, however, the drug of the present invention is not limited to the following examples.

[0204] Example 3: 5 g of sodium chlorite was dissolved in purified water to make 100 mL, yielding a 40,000 ppm sodium chlorite aqueous solution (Solution A). 0.1 g of benzethonium chloride was dissolved in 100 mL of purified water to make 100 mL of a 1,000 ppm aqueous solution (Solution B). A 0.1 M phosphate-NaOH buffer (pH = 9.5) was prepared. 20 mL of Solution A, diluted 10-fold, and 80 mL of buffer were added to 600 mL of purified water at pH 7, followed by 80 mL of Solution B, and purified water was added to make a total of 800 mL, yielding the agent of Example 3. This agent was an aqueous solution containing NaClO2 and benzethonium chloride. The pH of the agent of Example 3 thus produced was measured and found to be 7.5.

[0205] A drug was prepared in the same manner as in Example 3, except that the NaClO2 concentration was 100 mM and the benzethonium chloride concentration was 1.0 mM. This drug was sealed in an ESR tube, and the ESR (Electron Spin Resonance) spectrum was measured at -196°C using an electron spin spectrophotometer (JES-ME-LX X-band [product name] manufactured by JEOL Ltd.) to confirm the generation of chlorine dioxide radicals. Note that ESR and EPR (electron paramagnetic resonance) are synonymous. The measured ESR spectrum is shown in Figure 23. As shown, peaks indicating the presence of radicals appeared, confirming that ammonium benzethonium chloride (benzethonium chloride) acted as a radical-generating catalyst for sodium chlorite (NaClO2), generating chlorine dioxide radicals.

[0206] Example 4: 5 g of sodium chlorite was dissolved in purified water to make 100 mL, resulting in a 40,000 ppm sodium chlorite aqueous solution. 0.1 g of benzethonium chloride was dissolved in 100 mL of purified water to make a 1,000 ppm aqueous solution. The 40,000 ppm sodium chlorite aqueous solution was diluted 40 times to obtain a 1,000 ppm aqueous solution. 10 mL each of the sodium chlorite aqueous solution and the benzethonium chloride aqueous solution were mixed with 80 mL of purified water to make a 100 ppm aqueous solution, resulting in the agent of Example 4 (an aqueous solution containing NaClO2 and benzethonium chloride). The pH of the agent of Example 4 thus obtained was measured and found to be 7.5. Furthermore, ESR spectra of the agent of Example 4 were measured in the same manner as the agent of Example 3, and it was confirmed that benzethonium chloride (benzethonium chloride) acted as a radical-generating catalyst for sodium chlorite (NaClO2), generating chlorine dioxide radicals.

[0207] Comparative Example 1: Disinfectant containing sodium hypochlorite and water (commercially available product). Comparative Example 2: A disinfectant deodorizer containing sodium hypochlorite (commercially available product). Comparative Example 3: A disinfectant deodorizer containing hypochlorous acid and water (commercially available product). Comparative Example 4: A disinfectant deodorizer (commercially available product) containing sodium hypochlorite and water. Comparative Example 5: A disinfectant deodorizer (commercially available product) containing sodium hypochlorite and water. Comparative Example 6: Sodium chlorite standard solution 1000 ppm (test sample).

[0208] Comparative Example 7: 5 g of sodium chlorite (manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in 100 mL of purified water to prepare a 40,000 ppm aqueous solution, which was then further diluted with purified water to give a 100 ppm aqueous solution, and a test product according to Comparative Example 7 was obtained. Comparative Example 8: Benzethonium chloride aqueous solution (test sample).

[0209] (Experimental Example 1) In Experimental Example 1, the following were first prepared: Bacterial species used: Staphylococcus aureus Escherichia coli MV1184 Bacterial liquid: The bacteria grown on BHI agar medium were picked up with a platinum loop and placed in BHI liquid medium and shaken. 50 μL of the bacterial solution grown overnight in BHI liquid medium was diluted 190 times with BHI liquid medium, mixed, and stirred to prepare the bacterial solution.

[0210] Using the above, the effect (bactericidal action) was investigated as follows.

[0211] The microplate (with lid) was sterilized with a UV germicidal lamp for 10 minutes. Next, BHI liquid medium, the bacterial solution, and the agent according to Example 3 were sequentially injected into each well using a micropipette. After culturing at 37°C for 24 hours, the results were checked using a microplate reader to determine the MIC (minimum inhibitory concentration). Note that only the liquid medium was used as a control. In addition, 10 μL of the culture medium was taken from the well near the MIC, inoculated into a petri dish, and cultured at 37°C for 24 hours, and the MBC (minimum bactericidal concentration) was determined. The results are shown in Table 1.

[0212] The MIC and MBC were determined in the same manner using the disinfectant of Comparative Example 1 instead of the agent of Example 3. The results are shown in Table 1.

[0213] The MIC of Staphylococcus aureus was similarly determined using the disinfectant deodorants of Comparative Examples 2 to 5 instead of the agent of Example 3. The results are shown in Table 1.

[0214] The MIC for Staphylococcus aureus and the MIC and MBC for Escherichia coli were determined in the same manner using the test product of Comparative Example 6 instead of the agent of Example 3. The results are shown in Table 1.

[0215] [Table 1]

[0216] (Experimental Example 2) The MIC of E. coli was determined in the same manner using the drug of Example 4 or Comparative Example 7 or 8 instead of the drug of Example 3. The results are shown in Table 2.

[0217] [Table 2]

[0218] (Experimental Example 3) In Experimental Example 3, the following were first prepared: Bacterial species used: Streptococcus pyogenes Bacterial liquid: A bacterial solution was obtained in the same manner as in Experimental Example 1.

[0219] Using the above, MIC and MBC were determined using the drug of Example 3 in the same manner as in Experimental Example 1. The results are shown in Table 3.

[0220] [Table 3]

[0221] (Experimental Example 4) In Experimental Example 4, the following were first prepared: Bacterial species used: Cariogenic bacteria (Streptcoccus mutans) Bacterial liquid: The bacteria grown on BHI agar medium were picked up with a platinum loop and placed in BHI liquid medium and shaken. 50 μL of the bacterial solution grown overnight in BHI liquid medium was diluted 190 times with BHI liquid medium, mixed, and stirred to prepare the bacterial solution.

[0222] Using the above, the effects were investigated as follows.

[0223] The bacterial solution was injected into BHI liquid medium placed in two test tubes using a micropipette. Sucrose was added to a concentration of 0.2%. The mixture was cultured at 37°C for 18 hours to form a biofilm. The medium in the test tubes was discarded into a beaker and washed twice with PBS. The agent according to Example 3 and PBS were injected into each tube, and the mixture was shaken at 37°C for 30 minutes. The liquid in the test tubes was discarded into a beaker and washed twice with PBS. BHI liquid medium was poured into the test tubes and cultured at 37°C for 24 hours. 10 μL of each medium was spread on a nutrient agar medium and cultured at 37°C for 24 hours. The presence or absence of colonies was confirmed visually. As a result, no colonies were observed in the tube injected with the agent according to Example 3, but many colonies were observed in the tube injected with PBS.

[0224] To confirm the effect on the bacteria inside the biofilm, the following confirmation test was further carried out.

[0225] The bacterial solution was injected into BHI liquid medium placed in a microtube using a micropipette. Sucrose was added to a concentration of 0.2%. The mixture was cultured at 37°C for 18 hours to form a biofilm. The medium in the microtube was discarded into a beaker and washed twice with PBS. The agent according to Example 3 and PBS were injected into each tube, and the tubes were then cured at 37°C for 15 and 30 minutes. The liquid in the microtube was discarded into a beaker and washed twice with PBS. BHI liquid medium was poured into the test tube, homogenized, and then cultured at 37°C for 24 hours. 10 μL of each medium was spread on a nutrient agar medium and cultured at 37°C for 24 hours. The presence or absence of colonies was visually confirmed. As a result, no colonies were observed in the tube injected with the agent according to Example 3, but many colonies were observed in the tube injected with PBS. This demonstrates that the agent according to Example 3, when impregnated into a biofilm, acts deep within the biofilm and exhibits a bactericidal effect.

[0226] (Experimental Example 5) In Experimental Example 5, the following bacterial species were used, and the drug according to Example 3 was otherwise used in the same manner as in Experimental Example 1, and the MIC and MBC were determined. The results are shown in Table 4. Bacterial species used: Bacteria 1 (Porphyromonas gingivalis) Bacteria 2 (Treponema denticola) Bacteria 3 (Tannerella fosythensis) Bacteria 4 (Aggregatibacter actinomycetemcomitans)

[0227] [Table 4]

[0228] (Experimental Example 6) For iron, aluminum, tinplate, and stainless steel, each test piece (25.4 mm x 25.4 mm) was washed, then immersed in a resin container containing the agent according to Example 3, a 1.2% aqueous solution of sodium hypochlorite, and tap water, respectively, and then the resin container was capped. At the time intervals shown in Tables 5 and 6, the test pieces were removed onto a nonwoven fabric and the condition of the test pieces was visually inspected. Photographs were taken as necessary, and if changes were difficult to discern, they were observed under a microscope. The following criteria were used for evaluation.

[0229] -: No corrosion ±: Rust occurs +: Considerable amount of rust ++: A lot of rust +++: Corrosion of metal surfaces

[0230] [Table 5]

[0231] [Table 6]

[0232] (Experimental Example 7) The deodorizing performance test was conducted in accordance with the Japan Electrical Manufacturers' Association standard JEM1467 "Home Air Purifiers." The measurement was performed on a 1m3 container. 3The agitator was operated in an acrylic container (1 m long x 1 m wide x 1 m deep), and cigarettes were burned to fill the space with smoke. After all cigarettes had burned, the agitator was stopped, the sprayer was operated, and the agent of Example 3 was sprayed. The concentrations of the three components of ammonia, acetaldehyde, and acetic acid in the container were measured at regular intervals for two hours to track changes in concentration. Similarly, formaldehyde vapor was injected into the acrylic container, and the formaldehyde concentration in the container was measured at regular intervals for two hours to track changes in concentration. The sprayer was operated in 'Manual' mode. A blank test was also conducted as a control, with the sprayer not operating. The results are shown in Tables 7 to 10. Measurement of odor components was performed using a detector tube (manufactured by Gastec Corporation). The detector tube used is shown below.

[0233] Detector tube used Ammonia No. 3L Acetaldehyde No.92L Acetic acid No.81L Formaldehyde No.91

[0234] [Table 7]

[0235] [Table 8]

[0236] [Table 9]

[0237] [Table 10]

[0238] (Experimental Example 8) The agent of Example 3 was sprayed using a sprayer to measure its tobacco odor deodorizing performance. First, a cigarette was burned in a room equivalent to 6 tatami mats in size, filling the room with smoke to a constant concentration. Next, the sprayer was placed, and the odor intensity of the room was measured three times: before operation, one hour after operation, and two hours after operation. The sprayer was placed against the wall of the room, and odor was collected at a height of 1 m in the center of the room. Two stirring fans were installed in the room to keep the air constantly agitated. The sprayer was operated in 'Manual' mode. A blank test was also conducted as a control, in which the sprayer was not operated. The odor intensity was determined as follows using the 6-level odor intensity rating method. The results are shown in Table 11.

[0239] Six testers (panels) evaluated the odor intensity, and the results were calculated by averaging each intensity value. The six-level odor intensity rating is a method of quantifying odor strength using the human sense of smell. The panel conducting this test were those who underwent legally required olfactory tests and were deemed to have a normal sense of smell.

[0240] The six-level odor intensity rating system uses the following standard values: 0: Odorless 1: Very weak odor (detection threshold concentration) 2: Weak odor (perception threshold concentration) 3: Easily detectable odor 4: Strong odor 5: Very strong odor

[0241] [Table 11]

[0242] (Experimental Example 9) The agent of Example 3 was sprayed using a sprayer to measure the removal performance of airborne bacteria (general bacteria and fungi). First, the sprayer was placed in a room equivalent to 6 tatami mats in size, and the concentration of airborne bacteria in the air was measured three times: before operation, one hour after operation, and two hours after operation. The sprayer was placed near the wall of the room, and airborne bacteria were collected at a height of 1 m in the center of the room. Two stirring fans were installed in the room to keep the air constantly stirred. Airborne bacteria were measured using a filtration collection method using a membrane filter. The sprayer was operated in 'Manual' mode. A blank test was also conducted as a control, with the sprayer not operating. The results are shown in Tables 12 and 13.

[0243] Measurement conditions for Experimental Example 9 Filter used: Toyo Roshi Co., Ltd., 37mm monitor Suction air volume: 300L (suction at 20L per minute for 15 minutes) Culture medium: m-TGE Broth liquid medium for general bacteria (manufactured by Toyo Seisakusho) m-GreenY&M Broth liquid medium for fungi (manufactured by Toyo Seisakusho) Culture conditions: General bacteria 30℃ 72 hours Fungi 30℃ 5 days

[0244] [Table 12]

[0245] [Table 13]

[0246] (Experimental Example 10) In Experimental Example 10, the following bacterial species were used, and the drug according to Example 3 was used in the same manner as in Experimental Example 1, and the MIC or MBC was determined. The results are shown in Table 14. Bacterial species used: caries bacteria Streptococcus Bacillus subtilis Candida (Candida albicans)

[0247] [Table 14]

[0248] (Experimental Example 11) A deodorizing test was carried out using the agent of Example 3 in accordance with the Instrumental Analysis Implementation Manual: Detector Tube Method, Gas Chromatography Method (based on the Deodorizing Textile Product Certification Standards of the Japan Textile Evaluation Technology Council). The results are shown in Table 15.

[0249] [Table 15] Concentration 1: Initial gas concentration Concentration 2: Gas concentration after 2 hours Gas reduction rate: ((concentration 1 - concentration 2) / concentration 1) x 100

[0250] (Experimental Example 12) The drug of Example 3 was applied to the acne at a rate of about 2 mL several times a day for 14 days. As a result, it was clear that the application of the drug cured the acne, and it was confirmed that the drug of the present invention is useful as a therapeutic agent for acne.

[0251] Example 5: A drug according to Example 5 was prepared in the same manner as in Example 3, except that half the amount (molar amount) of ammonium chloride (NH4Cl) was used instead of benzethonium chloride as ammonium. The pH of this drug was measured and found to be 7.5. Furthermore, a drug was prepared in the same manner as in Example 5, except that the NaClO2 concentration was 100 mM and the ammonium chloride (NH4Cl) concentration was 0.5 mM. The ESR spectrum of this drug was measured in the same manner as in Example 3. The measured ESR spectrum is shown in Figure 24. As shown, peaks indicating the presence of radicals were observed, confirming that ammonium chloride (NH4Cl) acted as a radical-generating catalyst for sodium chlorite (NaClO2), generating chlorine dioxide radicals.

[0252] Example 6: The drug of Example 6 was obtained in the same manner as in Example 3, except that the same amount (molar number) of benzalkonium chloride (chemical formula below) was used instead of benzethonium chloride as the ammonium. The pH of this drug of Example 6 was measured and found to be 7.5. Furthermore, a drug was produced in the same manner as in Example 6, except that the NaClO2 concentration was 100 mM and the benzalkonium chloride concentration was 1.0 mM. The ESR spectrum of this drug was measured in the same manner as in Example 3. The measured ESR spectrum is shown in Figure 25. As shown, peaks indicating the presence of radicals were observed, confirming that benzalkonium chloride, an ammonium, acted as a radical-generating catalyst for sodium chlorite (NaClO2), generating chlorine dioxide radicals. [ka]

[0253] Example 7: The agent of Example 7 was obtained in the same manner as in Example 3, except that the same amount (molar number) of benzyltriethylammonium chloride (chemical formula below) was used instead of benzethonium chloride as the ammonium. The pH of this agent of Example 7 was measured and found to be 7.5. Furthermore, a drug was produced in the same manner as in Example 3, except that the NaClO2 concentration was 100 mM and the benzyltriethylammonium chloride concentration was 1.0 mM. The ESR spectrum of this agent was measured in the same manner as in Example 3. The measured ESR spectrum is shown in Figure 26. As shown, peaks indicating the presence of radicals appeared, confirming that benzyltriethylammonium chloride acted as a radical-generating catalyst for sodium chlorite (NaClO2), generating chlorine dioxide radicals. [ka]

[0254] Example 8: The drug of Example 7 was obtained in the same manner as in Example 3, except that the same amount (molar number) of methylammonium chloride was used instead of benzethonium chloride as the ammonium. The pH of this drug of Example 8 was measured and found to be 7.5. Furthermore, a drug was produced in the same manner as in Example 3, except that the NaClO2 concentration was 100 mM and the benzyltriethylammonium chloride concentration was 1.0 mM, and the ESR spectrum of this drug was measured in the same manner as in Example 3. As a result, peaks indicating the presence of radicals appeared, confirming that methylammonium chloride acted as a radical-generating catalyst for sodium chlorite (NaClO2) and generated chlorine dioxide radicals.

[0255] [Evidence data on Lewis acidity] (1) Measurement conditions As described above, the Lewis acidity of the ammonium salt was measured and calculated by the method described in J. Org. Chem. 2003, 68, 4720-4726. Specifically, the reaction rate of the oxidation of CoTPP using O2 as a radical source was determined as described in J. Org. Chem. 2003, 68, 4720-4726, from line 21 on page 4724 to line 6 on page 4724, and the Lewis acidity ΔE (eV) was calculated according to the linear relationship (y = 14(ΔE) - 8.0) given in the graph shown in Figure 6 on page 4725 (y is the common logarithm of the rate constant).

[0256] (2) Lewis acidity value The Lewis acidity values ​​measured and calculated by the method (1) above are shown below. Table 16 below shows the Lewis acidity values ​​of the four types of ammonium in Examples 3 to 7. Table 17 below shows the Lewis acidity values ​​of various other ammonium. In addition to Tables 16 and 17 below, the Lewis acidity of pralidoxime methyl iodide (PAM) was measured using the same method and was found to be 0.60 eV.

[0257] [Table 16]

[0258] [Table 17]

[0259] (Experimental Example 13) The bactericidal effects were confirmed using the agent of Example 5 containing ammonium chloride, the agent of Example 6 containing benzalkonium chloride, the agent of Example 7 containing benzyltriethylammonium chloride, and the agent of Example 8 containing methylammonium chloride.

[0260] The bactericidal effect was measured in the same manner as in Experimental Example 1, except that the agent of Example 3 (a drug containing benzethonium chloride and sodium chlorite) was replaced with the same amount of a drug containing ammonium chloride and sodium chlorite (Example 5), a drug containing benzalkonium chloride and sodium chlorite (Example 6), or a drug containing benzyltriethylammonium chloride and sodium chlorite (Example 7). The bacterial strain used was Escherichia coli (Escherichia coli MV1184). Furthermore, instead of the drug of Examples 5, 6, 7, or 8, an aqueous solution containing only ammonium chloride, benzalkonium chloride, benzyltriethylammonium chloride, or methylammonium chloride but not sodium chlorite (comparative example) was used to measure the bactericidal effect in the same manner.

[0261] (2) Measurement results of sterilization effect The results of the MIC (minimum inhibitory concentration) measured in the above (1) are shown in Table 18 below.

[0262] [Table 18]

[0263] As shown in Table 18, when using a drug containing ammonium chloride and sodium chlorite (Example 5), a drug containing benzalkonium chloride and sodium chlorite (Example 6), a drug containing benzyltriethylammonium chloride and sodium chlorite (Example 7), or a drug containing methylammonium chloride and sodium chlorite (Example 8), the bactericidal effect of the drug of the present invention was confirmed.In contrast, an aqueous solution containing only ammonium chloride, benzalkonium chloride, benzyltriethylammonium chloride, or methylammonium chloride but not sodium chlorite had no bactericidal effect.From this, it was confirmed that the bactericidal effect was achieved by the chlorine dioxide radicals generated from sodium chlorite by the catalytic action of ammonium chloride, benzalkonium chloride, benzyltriethylammonium chloride, or methylammonium chloride.

[0264] (Experimental Example 14: Suppression of symptoms of ulcerative colitis) A pH buffer was added to the drug of Example 3 to adjust the pH to 5.35. This drug will be referred to as "MA-T" hereinafter.

[0265] Next, approximately 12-week-old C57BL / 6J male mice (housed at the Osaka University Medical School Animal Facility 5-05) were administered 2% dextran sodium sulfate (DSS) solution (MP Biomedicals) via the anus using a disposable feeding needle (2 mm tip diameter, 1.18 mm tube diameter, 50 mm tube length) for 3 days before administration and on days 6-8, 10-12, and 14-16 after DSS administration. MA-T (pH 5.35) or vehicle (water only) was administered intrarectally in 150 μl increments. During this period, 2% DSS was provided in a water bottle and allowed to drink ad libitum. Six days after the start of 2% DSS administration, normal water was administered. Body weights were measured during the 2% DSS drinking period and the subsequent normal water drinking period. Weight loss after DSS administration was analyzed using the weight on the day of 2% DSS administration as the baseline. The results are shown in Figure 27. FIG. 27 shows the results of the male mouse *P<0.05 (t-test). The horizontal axis represents the number of days before or after the start of DSS administration, and the vertical axis represents the change in body weight (grams). In the figure, the dots represent the vehicle-administered (drinking water) group, and the circles represent the MA-T-administered group. As shown, after the start of 2% DSS administration, the mice continued to lose weight until MA-T or vehicle administration was initiated. This suggests that dextran sulfate sodium-induced colitis had developed. Subsequently, when MA-T or vehicle administration was initiated after the start of 2% DSS administration, body weight recovered (regained) in both groups. This suggests that dextran sulfate sodium-induced colitis was suppressed. Furthermore, the MA-T-administered group showed a greater degree of weight recovery (regain) than the vehicle-administered group. This suggests that MA-T administration suppressed dextran sulfate sodium-induced colitis more effectively than vehicle administration. That is, this Experimental Example confirmed that MA-T has an inhibitory effect on dextran sulfate sodium-induced colitis. From this, it can be inferred that MA-T has a bactericidal action (bactericidal effect). This was further confirmed in Experimental Example 15 below.

[0266] (Experimental Example 15: Changes in intestinal flora) In Experimental Example 14 (Figure 27), feces (3–5 pellets) were collected from the vehicle-treated and MA-T (pH 5.35)-treated groups immediately before DSS administration (the day of administration) and 16 days after administration. After measuring the fecal weight, RNAlater (RNAlater (ml) = fecal weight (g) × 9) (Invitrogen) was added, and a 10-fold (v / w) diluted fecal homogenate was prepared using a vortex mixer. 200 μl of the homogenate was transferred to a 2 ml screw-cap microtube, 1 ml of PBS(-) was added, and the mixture was stirred using a vortex mixer and centrifuged for 5 minutes at 4°C and 13,000 × g. The supernatant was removed, and 1 ml of PBS(-) was added again. The mixture was stirred using a vortex mixer and centrifuged for 5 minutes at 4°C and 13,000 × g. The supernatant was then removed. 0.3 g glass beads (0.1 mm diameter), 300 μL Tris-SDS solution (100 mM Tris-HCl, 40 mM EDTA (pH 9.0), 1% SDS), and 500 μL TE-saturated phenol (Nacalai) were added and mixed using a FastPrep (5.0 power level, 30 seconds) (MP Biomedicals). After 5 minutes of centrifugation (4°C, 20,000 × g), 400 μL of the supernatant was transferred to a 2 ml screw-cap microtube, and an equal volume of phenol / chloroform / isoamyl alcohol (25:24:1) (Nacalai) was added. The mixture was then mixed again using a FastPrep (4.0 power level, 45 seconds). After centrifugation for 5 minutes (4°C, 20,000 × g), 250 μl of the supernatant was transferred to a 1.5 ml screw-cap microtube, 25 μl of 3 M sodium acetate (pH 5.2) and 300 μl of isopropanol (Nacalai) were added, and the mixture was stirred using a vortex mixer. The mixture was then centrifuged for 5 minutes (4°C, 20,000 × g). The supernatant was removed, and 800 μl of 80% ethanol was added. The mixture was then centrifuged for 5 minutes (4°C, 20,000 × g). The supernatant was then removed, and the tube was placed in a 60°C block incubator for 30 minutes to dry. 200 μl of TE (pH 8.0) (Nacalai) was added to dissolve the recovered nucleic acid (DNA).Using the prepared DNA solution and enterobacteria standard plasmid DNA, the number of enterobacteria (Blautia cluster, Clostridium coccoides, Bacteroides fragilis) in 1 g of feces was analyzed by quantitative PCR ((1) 94°C 5 min, (2) 94°C 20 sec, (3) 55°C 20 sec, (4) 72°C 50 sec, (1) 1 cycle / (2)-(4) 45 cycles) (Step One Plus, Applied Biosystems). The primer sets used for PCR are as follows: Primer sets; Blautia cluster , 5'-gtgaaggaagaagtatctcgg-3' and 5'-ttggtaaggttcttcgcgtt-3'; Clostridium coccoides , 5'-aaatgacgggtacctgactaa-3' and 5'-ctttgagtttcattcttgcgaa-3'; Bacteroides fragilis , 5'-atagcctttcgaaagaagat-3' and 5'-ccagtatcaactgcaatttta-3'.

[0267] The bar graphs in Figure 28 show the number of bacteria detected. In each bar graph, "Day 0" represents the time immediately before DSS administration (the day administration began), and "Day 16" represents 16 days after administration began. In each graph, the left bar represents the vehicle-administered group, and the right bar represents the MA-T-administered group. The vertical axis represents the number of bacteria per gram (g) of feces. As shown in the figure, it was confirmed that MA-T induced changes in the intestinal bacterial flora. This confirmed that MA-T has a bactericidal action (bactericidal effect).

[0268] [Examples of agricultural and livestock pesticides] Next, specific examples of agricultural and livestock chemicals will be described. However, the agricultural and livestock chemicals of the present invention are not limited to the following examples. In the examples of the present invention, the agricultural and livestock chemicals of the examples may be simply referred to as "chemicals."

[0269] The agents of Examples 3 and 4 and Comparative Examples 1 to 8 were used as agricultural and livestock agents in the following experimental examples of agricultural and livestock agents.

[0270] (Experimental example 1 of agricultural and livestock drugs) In Experimental Example 1 of agricultural and livestock drugs, the following were first prepared. Bacterial species used: Staphylococcus aureus Escherichia coli MV1184 Bacterial liquid: The bacteria grown on BHI agar medium were picked up with a platinum loop and placed in BHI liquid medium and shaken. 50 μL of the bacterial solution grown overnight in BHI liquid medium was diluted 190-fold with BHI liquid medium, mixed, and stirred to prepare the bacterial solution.

[0271] Using the above, the effects were investigated as follows.

[0272] The microplate (with lid) was sterilized with a UV germicidal lamp for 10 minutes. Next, BHI liquid medium, bacterial solution, and the agricultural and livestock drug of Example 3 were sequentially injected into each well using a micropipette. After culturing at 37°C for 24 hours, the results were checked with a microplate reader to determine the MIC (minimum inhibitory concentration). Note that the liquid medium alone was used as a control. In addition, 10 μL of the culture medium was taken from the well near the MIC, inoculated into a petri dish, and cultured at 37°C for 24 hours, and the MBC (minimum bactericidal concentration) was determined. The results are shown in Table 19.

[0273] The MIC and MBC were determined in the same manner using the fungicide of Comparative Example 1 instead of the agricultural and livestock drug of Example 3. The results are shown in Table 19.

[0274] The MICs of Staphylococcus aureus were similarly determined using the disinfectants and deodorizers of Comparative Examples 2 to 5 instead of the agricultural and livestock drug of Example 3. The results are shown in Table 19.

[0275] The MIC for Staphylococcus aureus and the MIC and MBC for Escherichia coli were determined in the same manner using the test product of Comparative Example 6 instead of the agricultural and livestock drug of Example 3. The results are shown in Table 19.

[0276] [Table 19]

[0277] (Experimental example 2 of agricultural and livestock drugs) The MIC of Escherichia coli was determined in the same manner using the agricultural and livestock drug of Example 4 or Comparative Example 7 or 8 instead of the agricultural and livestock drug of Example 3. The results are shown in Table 20.

[0278] [Table 20]

[0279] (Experimental example 3 of agricultural and livestock drugs) In Experimental Example 3 on agricultural and livestock drugs, the following were first prepared: Bacterial species used: Streptococcus pyogenes Bacterial liquid: A bacterial solution was obtained in the same manner as in Experimental Example 1 for agricultural and livestock drugs.

[0280] Using the above, the MIC and MBC were determined using the agricultural and livestock drug of Example 3 in the same manner as in Experimental Example 1 for agricultural and livestock drugs. The results are shown in Table 21.

[0281] [Table 21]

[0282] (Experimental example 4 of agricultural and livestock drugs) In Experimental Example 4 on agricultural and livestock drugs, the following were first prepared: Bacterial species used: Streptococcus mutans Bacterial liquid: The bacteria grown on BHI agar medium were picked up with a platinum loop and placed in BHI liquid medium and shaken. 50 μL of the bacterial solution grown overnight in BHI liquid medium was diluted 190-fold with BHI liquid medium, mixed, and stirred to prepare the bacterial solution.

[0283] Using the above, the effects were investigated as follows.

[0284] The bacterial solution was injected into BHI liquid medium placed in two test tubes using a micropipette. Sucrose was added to a concentration of 0.2%. The mixture was cultured at 37°C for 18 hours to form a biofilm. The medium in the test tubes was discarded into a beaker and washed twice with PBS. The agricultural and livestock drug of Example 3 and PBS were injected into each tube, and the mixture was shaken at 37°C for 30 minutes. The liquid in the test tubes was discarded into a beaker and washed twice with PBS. BHI liquid medium was injected into the test tubes and cultured at 37°C for 24 hours. 10 μL of each medium was spread on a nutrient agar medium and cultured at 37°C for 24 hours. The presence or absence of colonies was confirmed visually. As a result, no colonies were observed in the tube injected with the agricultural and livestock drug of Example 3, but many colonies were observed in the tube injected with PBS.

[0285] To confirm the effect on the bacteria inside the biofilm, the following confirmation test was further carried out.

[0286] The bacterial solution was injected into BHI liquid medium placed in a microtube for mashing using a micropipette. Sucrose was added to a concentration of 0.2%. The mixture was cultured at 37°C for 18 hours to form a biofilm. The medium in the microtube was discarded into a beaker and washed twice with PBS. The agricultural livestock agent of Example 3 and PBS were injected into each tube, and the tubes were then cured at 37°C for 15 and 30 minutes. The liquid in the microtube was discarded into a beaker and washed twice with PBS. BHI liquid medium was poured into the test tube, homogenized, and then cultured at 37°C for 24 hours. 10 μL of each medium was plated on a nutrient agar medium and cultured at 37°C for 24 hours. The presence or absence of colonies was visually confirmed. As a result, no colonies were observed in the tubes injected with the agricultural livestock agent of Example 3, but many colonies were observed in the tubes injected with PBS. This demonstrates that the agricultural livestock agent of Example 3, when impregnated into a biofilm, acts deep within the biofilm and exhibits a bactericidal effect.

[0287] (Experimental example 5 of agricultural and livestock drugs) In Experimental Example 5 for agricultural and livestock chemicals, the following bacterial species were used, and the agricultural and livestock chemicals of Example 3 were used in the same manner as in Experimental Example 1 for agricultural and livestock chemicals, and the MIC and MBC were determined. The results are shown in Table 22. Bacterial species used: Bacteria 1 (Porphyromonas gingivalis) Bacteria 2 (Treponema denticola) Bacteria 3 (Tannerella forsythensis) Bacteria 4 (Aggregatibacter actinomycetemcomitans)

[0288] [Table 22]

[0289] (Experimental example 6 of agricultural and livestock drugs) For iron, aluminum, tinplate, and stainless steel, each test piece (25.4 mm x 25.4 mm) was washed and then immersed in a resin container containing the agricultural and livestock chemical of Example 3, a 1.2% aqueous solution of sodium hypochlorite, and tap water, respectively, and then the resin container was capped. At the time intervals listed in Tables 23 and 24, the test pieces were removed onto a nonwoven fabric and the condition of the test pieces was visually inspected. Photographs were taken as necessary, and if changes were difficult to discern, they were observed under a microscope. The evaluation was based on the following criteria.

[0290] -: No corrosion ±: Rust occurs +: Considerable amount of rust ++: A lot of rust +++: Corrosion of metal surfaces

[0291] [Table 23]

[0292] [Table 24]

[0293] (Experimental example 7 of agricultural and livestock drugs) The deodorizing performance test was conducted in accordance with the Japan Electrical Manufacturers' Association standard JEM1467 "Home Air Purifiers." The measurement was performed on a 1m3 container. 3The agitator was operated in an acrylic container (1 m long x 1 m wide x 1 m deep), and cigarettes were burned to fill the container with smoke. After all the cigarettes had burned, the agitator was stopped, and the sprayer was operated to spray the agricultural and livestock chemical of Example 3. The concentrations of the three components, ammonia, acetaldehyde, and acetic acid, in the container were measured at regular intervals for two hours to track changes in concentration. Similarly, formaldehyde vapor was injected into the acrylic container, and the formaldehyde concentration in the container was measured at regular intervals for two hours to track changes in concentration. The sprayer was operated in 'Manual' mode. A blank test was also conducted as a control, with the sprayer not operating. The results are shown in Tables 25 to 28. Measurement of odor components was performed using a detector tube (manufactured by Gastec Corporation). The detector tube used is shown below.

[0294] Detector tube used Ammonia No. 3L Acetaldehyde No.92L Acetic acid No.81L Formaldehyde No.91

[0295] [Table 25]

[0296] [Table 26]

[0297] [Table 27]

[0298] [Table 28]

[0299] (Experimental example 8 of agricultural and livestock drugs) The agricultural and livestock chemical of Example 3 was sprayed using a sprayer to measure its deodorizing performance against cigarette odor. First, a cigarette was burned in a room equivalent to 6 tatami mats in size, filling the room with smoke until a constant concentration was achieved. Next, the sprayer was placed, and the odor intensity of the room was measured three times: before operation, one hour after operation, and two hours after operation. The sprayer was placed against the wall of the room, and odor was collected from the center of the room at a height of 1 m. Two stirring fans were installed in the room to constantly stir the air. The sprayer was operated in 'Manual' mode. A blank test was also conducted as a control, in which the sprayer was not operated. The odor intensity was evaluated using the 6-level odor intensity rating system as follows. The results are shown in Table 29.

[0300] Six testers (panels) evaluated the odor intensity, and the results were calculated by averaging each intensity value. The six-level odor intensity rating is a method of quantifying odor strength using the human sense of smell. The panel conducting this test were those who underwent legally required olfactory tests and were deemed to have a normal sense of smell.

[0301] The six-level odor intensity rating system uses the following standard values: 0: Odorless 1: Very weak odor (detection threshold concentration) 2: Weak odor (perception threshold concentration) 3: Easily detectable odor 4: Strong odor 5: Very strong odor

[0302] [Table 29]

[0303] (Experimental example 9 of agricultural and livestock drugs) The agricultural and livestock chemical of Example 3 was sprayed using a sprayer to measure its performance in removing airborne bacteria (general bacteria and fungi). First, the sprayer was placed in a room equivalent to 6 tatami mats in size, and the concentration of airborne bacteria in the air was measured three times: before operation, one hour after operation, and two hours after operation. The sprayer was placed against the wall of the room, and airborne bacteria were collected from the center of the room at a height of 1 m. Two stirring fans were installed in the room to maintain constant stirring. Airborne bacteria were measured using a filtration collection method using a membrane filter. The sprayer was operated in 'Manual' mode. A blank test was also conducted as a control, with the sprayer not operating. The results are shown in Tables 30 and 31.

[0304] Measurement conditions for Experiment 9 of agricultural and livestock drugs Filter used: Toyo Roshi Co., Ltd., 37mm monitor Suction air volume: 300L (suction at 20L per minute for 15 minutes) Culture medium: m-TGE Broth liquid medium for general bacteria (manufactured by Toyo Seisakusho) m-GreenY&M Broth liquid medium for fungi (manufactured by Toyo Seisakusho) Culture conditions: General bacteria 30℃ 72 hours Fungi 30℃ 5 days

[0305] [Table 30]

[0306] [Table 31]

[0307] (Experimental example 10 of agricultural and livestock drugs) In Experimental Example 10 of the agricultural and livestock chemicals, the following bacterial species were used, and the agricultural and livestock chemicals of Example 3 were used in the same manner as in Experimental Example 1 of the agricultural and livestock chemicals, and the MIC or MBC was determined. The results are shown in Table 32. Bacterial species used: caries bacteria Streptococcus Bacillus subtilis Methicillin-resistant Staphylococcus aureus (MRSA)

[0308] [Table 32]

[0309] (Experimental example 11 of agricultural and livestock drugs) A deodorization test was carried out using the agricultural and livestock agent of Example 3 according to the description in the Instrumental Analysis Implementation Manual: Detector Tube Method, Gas Chromatography Method (based on the Deodorizing Textile Product Certification Standards of the Japan Textile Evaluation Technology Council). The results are shown in Table 33.

[0310] [Table 33] Concentration 1: Initial gas concentration Concentration 2: Gas concentration after 2 hours Gas reduction rate: ((concentration 1 - concentration 2) / concentration 1) x 100

[0311] (Experimental example 12 of agricultural and livestock drugs) By administering the agricultural and livestock drug of the present invention to mice, it was confirmed that the agricultural and livestock drug of the present invention is highly safe.

[0312] An acute oral toxicity test was conducted on mice using the agricultural and livestock drug of Example 3 based on the OECD TG420 acute oral toxicity test (fixed dose method). The test was conducted by the Japan Food Research Laboratories Foundation. As a result, the LD50 value of the agricultural and livestock drug was 2000 mg / kg or more for both males and females. This demonstrates that the agricultural and livestock drug of the present invention is extremely safe.

[0313] (Experimental example 13 of agricultural and livestock drugs) By administering the agricultural and livestock drug of the present invention to rabbits, it was confirmed that the agricultural and livestock drug of the present invention is highly safe.

[0314] The agricultural and livestock drug of Example 3 was used in an eye irritation test on rabbits in accordance with OECD TG405 Acute Eye Irritation / Corrosion. The test was conducted by the Japan Food Research Laboratories Foundation. As a result, it was found that the agricultural and livestock drug was a non-irritant. Therefore, it was found that the agricultural and livestock drug of the present invention is extremely safe.

[0315] (Experimental example 14 of agricultural and livestock drugs) By administering the agricultural and livestock drug of the present invention to rabbits, it was confirmed that the agricultural and livestock drug of the present invention is highly safe.

[0316] Using the agricultural and livestock drug of Example 3, a primary skin irritation test was conducted on rabbits in accordance with OECD TG404 Acute Skin Irritation / Corrosion. The test was conducted by the Japan Food Research Laboratories Foundation. As a result, it was found that the agricultural and livestock drug was a weak irritant. Therefore, it was found that the agricultural and livestock drug of the present invention is extremely safe.

[0317] (Experimental example 15 of agricultural and livestock drugs) By administering the agricultural and livestock drug of the present invention to guinea pigs, it was confirmed that the agricultural and livestock drug of the present invention is highly safe.

[0318] A continuous skin irritation test was conducted on guinea pigs by applying the agricultural and livestock drug of Example 3 for 14 consecutive days. The test was conducted by Life Science Research Institute Co., Ltd. As a result, it was found that the agricultural and livestock drug was a non-irritant. Therefore, it was found that the agricultural and livestock drug of the present invention is extremely safe.

[0319] (Experimental example 16 of agricultural and livestock drugs) By administering the agricultural and livestock drug of the present invention to guinea pigs, it was confirmed that the agricultural and livestock drug of the present invention is highly safe.

[0320] A skin sensitization test was conducted on guinea pigs using the agricultural and livestock drug of Example 3 by the Maximization Test method. The test was conducted by Life Science Research Institute Co., Ltd. As a result, it was found that the agricultural and livestock drug does not cause skin sensitization, and therefore the agricultural and livestock drug of the present invention is extremely safe.

[0321] (Experimental example 17 of agricultural and livestock drugs) By administering the agricultural and livestock drug of the present invention to humans, it was confirmed that the agricultural and livestock drug of the present invention is highly safe.

[0322] A human patch test was conducted using the agricultural and livestock drug of Example 3 by applying a patch onto a human body for 24 hours. The test was conducted by Life Science Research Institute Co., Ltd. As a result, it was found that the agricultural and livestock drug was non-irritating. Therefore, it was found that the agricultural and livestock drug of the present invention is extremely safe.

[0323] (Experimental example 18 of agricultural and livestock drugs) It was confirmed that the agricultural and livestock agent of the present invention can suppress the occurrence of rice blast disease.

[0324] Koshihikari rice seeds were screened in salt water, and floating rice seeds were removed to remove diseased rice seeds. The obtained rice seeds were then washed with water, drained, and packed into coarse-grained plastic bags. Next, the agricultural and livestock chemical of Example 3 was diluted 200 times to prepare a diluted solution (hereinafter also referred to as "200-fold solution"). The rice seeds packed in the plastic bags were then soaked for 24 hours in the 200-fold solution, which was twice the weight of the rice seeds. Water was not exchanged during the soaking treatment. After the soaking treatment, the rice seeds were air-dried and then soaked again for 6 days. Water was not exchanged during the soaking treatment. After the soaking treatment, the rice seeds were soaked again for 6 days.

[0325] Next, the rice seeds were sown in seedling boxes, and 500 mL of the 200x solution was sprayed per seedling box before the seedlings were raised. The resulting seedlings were planted in rice paddies and cultivated in the usual manner. The occurrence of rice blast during cultivation was then confirmed. As a control, Hitomebore rice seeds were used instead of the Koshihikari rice, and the occurrence of rice blast was confirmed in the same manner, except that they were not soaked in the 200x solution and planted in a paddy field adjacent to the Koshihikari rice field.

[0326] As a result, no occurrence of rice blast was confirmed in the rice fields that had been immersed in the 200x solution. In contrast, occurrence of rice blast was confirmed in the control. These results demonstrate that the agricultural and livestock chemical agent of the present invention can suppress the occurrence of rice blast.

[0327] (Experimental example 19 of agricultural and livestock drugs) It was confirmed that the agricultural and livestock drug of the present invention can suppress the spread of rice blast disease.

[0328] During the puddling of rice fields where blast disease was prevalent, 10 L of a 10-fold diluted solution of the agricultural and livestock chemical agent from Example 3 (hereinafter also referred to as the "10x solution") was added per 10 ares of the rice field, and puddling was carried out. Next, Koshihikari seedlings from Experimental Example 18 of the agricultural and livestock chemical agent were planted in the puddled rice field and cultivated. If blast disease was confirmed during cultivation, the blast-infected rice plants were removed, and 1 L of the 10x solution per 10 ares of the rice field was sprayed around the area where the blast-infected rice plants had been cultivated. As a control, the control seedlings from Experimental Example 18 of the agricultural and livestock chemical agent were used instead of the Koshihikari seedlings from Experimental Example 18 of the agricultural and livestock chemical agent. The 10x solution was not added or sprayed in the rice field, and the control seedlings were planted in a rice field adjacent to the Koshihikari seedlings, and cultivation was similar. Then, it was confirmed whether the rice blast disease that had occurred in the rice field planted with the control during the cultivation would spread to the rice field planted with the Koshihikari seedlings.

[0329] As a result, the occurrence and spread of blast was observed in the rice fields planted with the control. In contrast, in the rice fields planted with Koshihikari seedlings, slight occurrence of blast was observed above the primary rachis branches in an area about 2-3 m adjacent to the rice fields planted with the control, but the spread of blast to other parts of the rice field was not observed. These results demonstrate that the agricultural and livestock pesticide of the present invention can suppress the spread of blast.

[0330] (Experimental example 20 of agricultural and livestock drugs) It was confirmed that the agricultural and livestock agent of the present invention can repel stink bugs and other pests.

[0331] In the same manner as in Experimental Example 19 of the agricultural and livestock chemicals, 23 farmers each treated one rice field, but the Koshihikari seedlings from Experimental Example 18 of the agricultural and livestock chemicals were planted in the rice fields and cultivated. After cultivation, each farmer was interviewed about the frequency of stink bugs and other pests approaching their rice fields compared to previous years.

[0332] As a result, eight farmers responded that they had observed stink bugs and other pests being repelled. These findings demonstrate that the agricultural and livestock agent of the present invention can repel stink bugs and other pests.

[0333] [Examples of amino acids, peptides and phospholipids] Examples of amino acids, peptides and phospholipids are described below.

[0334] [Reference example 6] Using the "Lewis Acidity Measurement Method (2)" described above, the reaction rate constants of various amino acids, peptides, and phospholipids were measured as follows. In the table below, "L-aspartate" represents L-aspartic acid, "L-glutamate" represents L-glutamic acid, "L-glycine" represents L-glycine, "L-lysine" represents L-lysine, "L-arginine" represents L-arginine, "GSSG" represents oxidized glutathione, "Cys-Cys" represents cystine, "DPPS" represents dipalmitoylphosphatidylserine, "DPPC" represents dipalmitoylphosphatidylcholine, and "adenine" represents adenine. In addition, "K obs " is the reaction rate constant (k cat As shown in the table below, it was confirmed that all of the amino acids, peptides, and phospholipids exhibited Lewis acidity.

[0335] [Table tpp2]

[0336] [Reference example 7] The Lewis acidity of phosphatidylserine, phosphatidylcholine, phosphatidic acid, phosphatidylethanolamine, phosphatidylglycerol, cardiolipin, L-aspartic acid, and L-serine was measured using "Lewis Acidity Measurement Method (1)" or "Lewis Acidity Measurement Method (2)," respectively. As a result, the Lewis acidity of phosphatidylserine, phosphatidylcholine, and L-aspartic acid was confirmed by both "Lewis Acidity Measurement Method (1)" and "Lewis Acidity Measurement Method (2)." The Lewis acidity of phosphatidic acid was confirmed by "Lewis Acidity Measurement Method (2)." The Lewis acidity of cardiolipin was confirmed by "Lewis Acidity Measurement Method (1)." Furthermore, the Lewis acidity of the sphingolipids (phospholipids) ganglioside GM1 and sphingomyelin was confirmed by "Lewis Acidity Measurement Method (2)."

[0337] [Example 9] Chlorine dioxide radicals were produced from chlorous acid or its salt (sodium chlorite) using various amino acids, peptides, and phospholipids whose Lewis acidities were measured in Reference Examples 6 and 7. This confirmed that the various amino acids, peptides, and phospholipids act as chlorine dioxide radical-generating catalysts for chlorous acid or its salt (sodium chlorite).

[0338] [Example 10] Using the various ammonium compounds, drugs were produced in the same manner as in Examples 3 to 8. Drugs were also produced in the same manner as in Examples 3 to 8, except that the various amino acids, peptides, and phospholipids whose Lewis acidity was measured in Reference Examples 6 and 7 were used instead of the various ammonium compounds. Furthermore, these drugs were used in the same manner as in the experimental examples for the drug compounds and the experimental examples for agricultural and livestock drugs, and it was confirmed that they had bactericidal activity and the like.

[0339] The preparation of the agent was carried out as follows. First, sodium chlorite was dissolved in purified water to obtain a sodium chlorite aqueous solution (Solution A). Meanwhile, each of the ammonium, amino acids, peptides, and phospholipids was dissolved in purified water to obtain an aqueous solution (Solution B). Then, Solution A at a concentration of 1 mM was mixed with Solution B at a concentration of 0.2 mM, or Solution A at a concentration of 5 mM was mixed with Solution B at a concentration of 1 mM, and the mixture was further diluted to obtain a agent. The concentration of each of the ammonium, amino acids, peptides, or phospholipids in the agent was 12.5 to 20 ppm. The concentration of sodium chlorite in the agent was approximately 0.14 to 0.22 mM.

[0340] Bacterial species used: Escherichia coli MV1184 Bacterial liquid: The bacteria grown on BHI agar medium were picked up with a platinum loop and placed in BHI liquid medium and shaken. 50 μL of the bacterial solution grown overnight in BHI liquid medium was diluted 190 times with BHI liquid medium, mixed, and stirred to prepare the bacterial solution.

[0341] Using the above, the effect (bactericidal action) was investigated as follows.

[0342] A microplate (with lid) was sterilized for 10 minutes using a UV germicidal lamp. Next, BHI liquid medium, the bacterial solution, and the drug were sequentially injected into each well using a micropipette. After 24 hours of incubation at 37°C, the wells were checked using a microplate reader to determine the MIC (minimum inhibitory concentration). The control was liquid medium alone. Also, 10 μL of culture medium was taken from a well near the MIC, inoculated into a petri dish, and incubated at 37°C for 24 hours to determine the MBC (minimum bactericidal concentration). Furthermore, as a control, instead of the drug, solution A alone (aqueous solution of sodium chlorite only: sodium chlorite concentration 40 ppm, approximately 0.44 mM) or solution B alone (aqueous solution of each of the ammonium, amino acid, peptide, or phospholipid only) was used to similarly examine its efficacy (bactericidal activity).

[0343] As a result of investigating the bactericidal activity as described above, it was confirmed that the ammonium compounds methylammonium chloride, ammonium chloride, tetrabutylammonium chloride, benzethonium chloride, and benzalkonium chloride, the amino acids glycine, L-serine, L-aspartic acid, and proline, the peptide oxidized glutathione, and the phospholipid choline each have bactericidal activity (germicidal effect).

[0344] On the other hand, when only Solution A or only Solution B was used, there was no bactericidal action (sterilizing effect). In other words, it can be inferred that sodium chlorite alone, or each of the above ammonium, amino acid, peptide or phospholipid alone does not exhibit bactericidal action, but when both are present together, each of the above ammonium, amino acid, peptide or phospholipid reacts with sodium chlorite to generate chlorine dioxide radicals, and that these chlorine dioxide radicals exhibit bactericidal action.

[0345] Although the present invention has been described above with reference to the embodiments and examples, the present invention is not limited to the above embodiments and examples. Various modifications that can be understood by those skilled in the art can be made to the configuration and details of the present invention within the scope of the present invention. [Industrial Applicability]

[0346] As explained above, the radical-generating catalyst and radical-producing method of the present invention can generate (produce) radicals under mild conditions. The radical-generating catalyst and radical-producing method of the present invention can be used, for example, in the method for producing an oxidation reaction product of the present invention. The method for producing an oxidation reaction product of the present invention can be applied to oxidation reactions of various substances to be oxidized, including organic compounds and inorganic substances, and has a wide range of applications. Furthermore, the use of the radical-generating catalyst and radical-producing method of the present invention is not limited to the method for producing an oxidation reaction product of the present invention, but can be used in a wide range of applications.

[0347] Furthermore, according to the present invention, it is possible to provide a drug and an agricultural and livestock drug that are highly safe and have a high bactericidal effect. The uses of the drug and agricultural and livestock drug of the present invention are not particularly limited and can be used for a wide range of purposes. The drug and agricultural and livestock drug of the present invention are extremely useful, for example, in the fields of agriculture and livestock farming.

Claims

1. A radical generating catalyst that catalyzes radical generation from a radical generating source, The radical-generating catalyst contains an ammonium salt (excluding peroxodisulfate) represented by the following chemical formula (XI), and the Lewis acidity of the ammonium salt is 0.4 eV or more and 20 eV or less: the radical-generating catalyst is used to catalyze radical generation from the radical-generating source in an acidic liquid having a pH of 5.5 or more and less than 7.0; The radical generating catalyst is characterized in that the radical generating source is at least one selected from the group consisting of a halous acid, a halous acid ion, and a halous acid salt. 【XII】 In the chemical formula (XI), R １１ , R ２１ , R ３１ , and R ４１ , each represent a hydrogen atom or an aromatic ring, or an alkyl group, and the alkyl group may contain an ether bond, a carbonyl group, an ester bond, an amide bond, or an aromatic ring; R １１ , R ２１ , R ３１ , and R ４１ may be the same or different, Or, R １１ , R ２１ , R ３１ , and R ４１ Two or more of these are united and bonded to N ＋ and forming a cyclic structure together with the aryl group, the cyclic structure may be saturated or unsaturated, may be an aromatic ring or a non-aromatic ring, and may or may not have one or more substituents; X － is an anion (excluding peroxodisulfate).

2. In the ammonium salt represented by the chemical formula (XI), R １１ , R ２１ , R ３１ , and R ４１ , each represents a hydrogen atom or an alkyl group, and R １１ , R ２１ , R ３１ , and R ４１ may be the same or different, The radical generating catalyst according to claim 1.

3. 3. The radical generating catalyst according to claim 2, wherein the alkyl group is an alkyl group having 1 to 40 carbon atoms.

4. 3. The radical generating catalyst according to claim 2, wherein the alkyl group is an alkyl group having 1 to 6 carbon atoms.

5. The radical-generating catalyst according to any one of claims 1 to 4, wherein the ammonium salt represented by chemical formula (XI) is an ammonium salt represented by the following chemical formula (XII): 【Chemical XII】 In the chemical formula (XII), R １１１ is an alkyl group having 5 to 40 carbon atoms, which may contain an ether bond, a carbonyl group, an ester bond, an amide bond, or an aromatic ring, R ２１ and X － is the same as the above chemical formula (XI).

6. 2. The radical-generating catalyst according to claim 1, wherein the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XIII): 【XIII】 In the chemical formula (XIII), R １１１ is an alkyl group having 5 to 40 carbon atoms, and X － is the same as the above chemical formula (XI).

7. The radical-generating catalyst according to any one of claims 1 to 4, wherein the ammonium salt represented by chemical formula (XI) is an ammonium salt represented by the following chemical formula (XIV): 【XIV】 In the chemical formula (XIV), R １００ form a cyclic structure, which may be saturated or unsaturated, aromatic or non-aromatic, and may or may not contain one or more substituents; R １１ and X － is the same as the above chemical formula (XI).

8. The radical-generating catalyst according to any one of claims 1 to 4, wherein the ammonium salt represented by chemical formula (XI) is an ammonium salt represented by the following chemical formula (XV): 【XV】 In the chemical formula (XV), each Z is CH or N, and may be the same or different, and in the case of CH, H may be substituted with a substituent; R １１ and X － is the same as the above chemical formula (XI).

9. The radical-generating catalyst according to any one of claims 1 to 4, wherein the ammonium salt represented by chemical formula (XI) is an ammonium salt represented by the following chemical formula (XVI): 【XVI】 In the chemical formula (XVI), R １０１ , R １０２ , R １０３ , and R １０４ are each a hydrogen atom or a substituent, and R １０１ , R １０２ , R １０３ , and R １０４ may be the same or different, Or, R １０１ , R １０２ , R １０３ , and R １０４ Two or more of these are integrated, N to which they bond ＋ and forming a cyclic structure together with the ring, the cyclic structure may be saturated or unsaturated, may be an aromatic ring or a non-aromatic ring, and may or may not have one or more substituents; Z is CH or N, and in the case of CH, H may be substituted with a substituent; R １１ and X － is the same as the above chemical formula (XI).

10. The radical-generating catalyst according to any one of claims 1 to 4, wherein the ammonium salt represented by chemical formula (XI) is an ammonium salt represented by the following chemical formula (XVII): 【XVII】 In the chemical formula (XVII), R １１１ ~R １１８ are each a hydrogen atom or a substituent, and R １１１ ~R １１８ may be the same or different, Or, R １１１ ~R １１８ two or more of these may be combined together to form a cyclic structure, and the cyclic structure may be an aromatic ring or a non-aromatic ring, and may or may not have one or more substituents; Z is CH or N, and in the case of CH, H may be substituted with a substituent; R １１ and X － is the same as the above chemical formula (XI).

11. A radical generating catalyst that catalyzes radical generation from a radical generating source, comprising: Benzethonium chloride, benzalkonium chloride, hexadecyltrimethylammonium chloride, tetramethylammonium chloride, ammonium chloride, methylammonium chloride, tetrabutylammonium chloride, cetylpyridinium chloride, hexadecyltrimethylammonium bromide, dequalinium chloride, edrophonium, didecyldimethylammonium chloride, benzyltriethylammonium chloride, oxitropium, carbachol, glycopyrronium, safranine, sinapine, tetraethylammonium bromide the composition contains at least one ammonium salt (excluding peroxodisulfates) selected from the group consisting of ammonium, hexadecyltrimethylammonium bromide, suxamethonium, sphingomyelin, ganglioside GM1, denatonium, trigonelline, neostigmine, paraquat, pyridostigmine, phellodendrine, pralidoxime methyl iodide, betaine, betanin, bethanechol, lecithin, and cholines, and the Lewis acidity of the ammonium salt is 0.4 eV or more and 20 eV or less; The radical-generating catalyst is used to catalyze radical generation from a radical-generating source in an acidic liquid having a pH of 5.5 or more and less than 7.0, The radical generating catalyst is characterized in that the radical generating source is at least one selected from the group consisting of a halous acid, a halous acid ion, and a halous acid salt.

12. The radical-generating catalyst according to any one of claims 1 to 11, wherein the ammonium salt is a hexafluorophosphate salt of the ammonium.

13. The radical generating catalyst according to any one of claims 1 to 12, wherein the ammonium salt is benzethonium chloride.

14. The ammonium salt is NH ４ ＋ The radical generating catalyst according to claim 1 or 12, which is a salt of

15. The ammonium salt is NH ４ The radical generating catalyst according to claim 1, wherein the radical generating catalyst is Cl.

16. The radical generating catalyst according to any one of claims 1 to 15, wherein the haloid acid is at least one selected from the group consisting of chlorous acid, bromous acid, and iodous acid.

17. The radical generating catalyst according to any one of claims 1 to 16, wherein the radical generating source is a chlorite ion.

18. A method for producing radicals, comprising a mixing step of mixing the radical-generating catalyst according to claim 1 with the radical-generating source.

19. The method according to claim 18, further comprising mixing a solvent in the mixing step.

20. The method according to claim 18 or 19, further comprising a light irradiation step of irradiating the mixture obtained in the mixing step with light.

21. The method for producing radicals according to any one of claims 18 to 20, further comprising a reaction step of reacting the radical-generating catalyst with the radical-generating source in an acidic solution having a pH of 5.5 or more and less than 7.

0.

22. A method for producing an oxidation reaction product by oxidizing an oxidizable substance, comprising the steps of: a radical production step of producing the radical by the production method according to any one of claims 18 to 21; an oxidation reaction step in which the oxidized material is reacted with an oxidizing agent by the action of the radicals to generate the oxidation reaction product; A manufacturing method comprising:

23. The method according to claim 22, wherein the radical also serves as the oxidizing agent.

24. A liquid agent comprising a radical generating catalyst and at least one radical generating source selected from the group consisting of a halous acid, a halous acid ion, and a halous acid salt; The radical generating catalyst is the radical generating catalyst according to any one of claims 1 to 17, The radical generating catalyst is a drug that catalyzes the generation of radicals from the radical generating source in an acidic liquid having a pH of 5.5 or more and less than 7.

0.

25. 25. The drug according to claim 24, which is an acidic liquid drug having a pH of 5.5 or more and less than 7.

0.

26. The agent according to claim 24 or 25, wherein the halo acid is at least one selected from the group consisting of chlorous acid, bromous acid, and iodous acid.

27. 27. The agent according to any one of claims 24 to 26, wherein the halous acid is chlorous acid.

28. 28. The agent according to any one of claims 24 to 27, further comprising at least one of water and an organic solvent.

29. 29. The pharmaceutical composition of any one of claims 24 to 28, further comprising a pH buffering agent.

30. 30. An agent according to any one of claims 24 to 29 which is a disinfectant.

31. 31. The pharmaceutical agent according to any one of claims 24 to 30, for use in vivo.

32. 32. The pharmaceutical agent according to any one of claims 24 to 31 for use in the digestive tract.

33. The drug according to claim 32, wherein the digestive organ is at least one selected from the group consisting of the oral cavity, pharynx, esophagus, stomach, duodenum, small intestine, and large intestine.

34. The drug according to claim 32, wherein the digestive organ is the large intestine.

35. A drug according to any one of claims 32 to 34, for use in treating or suppressing the symptoms of ulcerative colitis.

36. The agent according to any one of claims 24 to 35, which is an agricultural and livestock agent.

37. The agricultural and livestock drug according to claim 36, wherein the agricultural and livestock drug is at least one selected from the group consisting of agricultural fungicides, agricultural antivirals, agricultural deodorizers, agricultural insecticides, agricultural repellents, agricultural soil conditioners, livestock fungicides, livestock antivirals, livestock deodorizers, livestock insecticides, livestock repellents, and livestock soil conditioners.

38. The agent described in any one of claims 24 to 30 is used for at least one purpose selected from the group consisting of suppression or prevention of rice blast disease, suppression or prevention of sheath blight, suppression or prevention of rice koji disease, suppression or prevention of rice blight, stink bug repellent or insect control, pest repellent or insect control, suppression or prevention of scab disease, suppression or prevention of powdery mildew, suppression or prevention of respiratory diseases, suppression or prevention of foot-and-mouth disease, and suppression or prevention of mastitis.

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