Application of pyrazole ring trinuclear silver (I) complex in organic molecular structure determination

Abstract

The application discloses application of a pyrazole ring trinuclear silver (I) complex in organic molecular structure determination, in particular, application of a 3,5-bistrifluoromethyl pyrazole ring trinuclear silver (I) complex in organic molecular structure determination, and specifically comprises the following steps: synthesizing the pyrazole ring trinuclear silver (I) complex; mixing the pyrazole ring trinuclear silver (I) complex with a sample to be measured, obtaining a co-crystal of the pyrazole ring trinuclear silver (I) complex and the organic molecule to be measured and performing single crystal diffraction analysis, collecting crystal data of the co-crystal; analyzing the crystal structure according to diffraction data of the co-crystal, so as to obtain a chemical structure and a stereo configuration of the organic molecule to be measured. The application can be used for molecular structure determination of a series of non-crystalline compounds and mixture samples.

Description

TECHNICAL FIELD

[0001] The application relates to application of a pyrazole ring trinuclear silver (I) complex in organic molecular structure determination and belongs to the technical field of organic molecular structure identification. BACKGROUND

[0002] Structure identification plays an important role in the fields of chemistry and pharmacy. Single crystal X-ray diffraction (SCXRD) can provide a clear three-dimensional structure of a crystal compound at an atomic level and is considered as the most reliable structure identification method. However, an inherent limitation of using SCXRD for structure identification for a long time is that a single crystal with a proper size and good diffraction is usually difficult to obtain. Many compounds, such as low-melting-point compounds, amorphous powders, amorphous solid compounds and trace-abundance natural products, are often difficult to characterize their structures by SCXRD technology due to their crystallization difficulty.

[0003] To solve the problem of organic molecular structure identification, Makoto Fujita's team first reported a method for identifying the structure of a compound by using a 'crystal sponge' (Nature, 2013, 495, 461-466). The method uses the highly regular channels of a metal-organic framework to absorb target organic molecules. The absorbed organic molecules are orderly arranged in the channels of the metal-organic framework through host-guest interactions, and the structure of the target organic molecules can be determined by SCXRD analysis. Subsequently, a series of metal-organic frameworks, porous organic materials or supramolecular cages with similar crystal sponge properties have been reported (ACS Cent. Sci., 2021, 7, 406-414; Angew. Chem. Int. Ed., 2021 60, 25204-25222). However, the size of the cavities / channels of most crystal sponges is limited, which hinders the entry of complex organic molecules. In addition, the stability of the crystal sponge in many solvents is poor, making it difficult to identify more types of organic molecules. At the same time, the cumbersome solvent exchange in the process of absorbing target organic molecules, the low occupancy of target organic molecules and the serious disorder of the crystal further limit its application.

[0004] Forming a co-crystal with a target molecule through non-covalent interaction using a crystallization partner is another strategy to solve the structure identification of difficult-to-crystallize compounds. In order to identify the structure of a difficult-to-crystallize organic molecule by using this method, a broad-spectrum crystallization partner capable of forming a co-crystal with organic molecules of different properties, sizes and complexities is needed, however, such a broad-spectrum crystallization partner has not been disclosed. SUMMARY

[0005] The application provides application of a pyrazole ring trinuclear silver (I) complex in organic molecular structure determination, which is suitable for molecular structure determination of difficult-to-crystallize compounds, amorphous compounds or mixture samples.

[0006] In order to achieve the above-mentioned purpose, the technical scheme adopted by the present application is: application of a pyrazole ring trinuclear silver (I) complex in organic molecular structure determination, wherein the pyrazole ring trinuclear silver (I) complex is a 3,5-bistrifluoromethyl pyrazole ring trinuclear silver (I) complex.

[0007] A method for organic molecular structure determination, comprising the following steps: mixing a pyrazole ring trinuclear silver (I) complex with a sample to be determined to obtain a co-crystal of the pyrazole ring trinuclear silver (I) complex and an organic molecule in the sample to be determined, and performing single crystal diffraction analysis on the co-crystal to obtain crystal diffraction data of the co-crystal; and analyzing the crystal structure according to the crystal diffraction data of the co-crystal, so as to obtain the chemical structure and stereo-configuration of the organic molecule to be determined.

[0008] Further, the pyrazole ring trinuclear silver (I) complex is a 3,5-bistrifluoromethyl pyrazole ring trinuclear silver (I) complex, which is synthesized by using 3,5-bistrifluoromethyl pyrazole and silver oxide.

[0009] Further, the analyzing of the crystal structure according to the crystal diffraction data of the co-crystal specifically comprises the following steps: determining the positions of part of non-hydrogen atoms by using a direct method, and then obtaining the coordinates of all non-hydrogen atoms by using a difference function method and a least square method; after obtaining the coordinates of all non-hydrogen atoms, further identifying the atom types and structure refinement, and obtaining the coordinates of all hydrogen atoms by using a theoretical hydrogenation method.

[0010] Further, after mixing the pyrazole ring trinuclear silver (I) complex with the sample to be determined in an organic solvent, the co-crystal of the pyrazole ring trinuclear silver (I) complex and the organic molecule to be determined is cultured under light-proof conditions; the temperature for the culture of the co-crystal is-25℃-150℃.

[0011] Further, the molar ratio of the pyrazole ring trinuclear silver (I) complex to the sample to be determined is 1:10-10:1.

[0012] Further, the organic solvent is one or more of methanol, ethanol, acetonitrile, dichloromethane, trichloromethane, cyclohexane, petroleum ether, acetone, diethyl ether, benzene, ethyl acetate, toluene, isopropyl alcohol and 1,4-dioxane.

[0013] Further, the temperature for the single crystal diffraction analysis is-173℃-room temperature.

[0014] Further, the co-crystal is obtained by using one of a solvent evaporation method, a solvent diffusion method, a gas phase diffusion method and a solvothermal method.

[0015] The present application can be used to determine the structures of non-crystalline compounds and multi-chiral complex compounds under mild conditions (room temperature).

[0016] The present application adopts pyrazole ring trinuclear silver (I) complex as a crystallization partner of an organic molecule, analyzes the structure of the organic molecule by obtaining a co-crystal of the pyrazole ring trinuclear silver (I) complex and the organic molecule, thereby omitting the steps of chromatographic separation and spectral identification of the mixture, and making the identification of the organic molecule more convenient and efficient. Meanwhile, the pyrazole ring trinuclear silver (I) complex is used to co-crystallize the organic molecule, and high-temperature melting or solvent thermal method is not required to culture the crystal, further simplifying the structure identification of the organic molecule.

[0017] For some to-be-detected organic molecules containing only light elements such as CHON, it is difficult to determine the absolute configuration thereof, but after the to-be-detected organic molecule is co-crystallized by the pyrazole ring trinuclear silver (I) complex, the absolute configuration thereof can be determined by the chirality of the whole crystal. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 is a crystal structure diagram of Ag3Pz3 in the present application;

[0019] Figure 2 is a crystal structure diagram of Ag3Pz3·trans-anethol in Example 1 of the present application;

[0020] Figure 3 is a crystal structure diagram of Ag3Pz3·chrysophanol in Example 2 of the present application;

[0021] Figure 4 is a crystal structure diagram of Ag3Pz3·7-hydroxy-5-methoxy-6,8-dimethylflavanone in Example 3 of the present application;

[0022] Figure 5 is a crystal structure diagram of Ag3Pz3·ammothamnine in Example 4 of the present application;

[0023] Figure 6 is a crystal structure diagram of Ag3Pz3·santonin in Example 5 of the present application;

[0024] Figure 7 is a crystal structure diagram of Ag3Pz3·spironolactone in Example 6 of the present application;

[0025] Figure 8 is a crystal structure diagram of Ag3Pz3·1 in Example 7 of the present application;

[0026] Figure 9 is a crystal structure diagram of Ag3Pz3·2 in Example 7 of the present application;

[0027] Figure 10A crystal structure diagram of Ag3Pz3 in the embodiment 7 of the present application;

[0028] Figure 11 A crystal structure diagram of Ag3Pz3 in the embodiment 7 of the present application; DETAILED DESCRIPTION

[0029] In order to better understand the essence of the present application, the present application will be further described below in conjunction with specific embodiments and drawings.

[0030] Cyclotriade complexes are a class of planar coordination compounds composed of three monovalent coin metal cations and three heterocyclic bridging ligands (Chem. Rev., 2020, 120, 9675-9742; Chem. Commun., 2019, 55, 7134-7146). Due to their unique supramolecular interactions (such as metalophilic interaction and π-acid···base interaction), such complexes are prone to form crystalline aggregates with themselves or other molecules, and their structures can be analyzed by single crystal X-ray diffraction. By changing the metal ions, organic ligands and substituents on the ligands, the π-acid / base and metalophilic properties of cyclotriade complexes can be widely regulated, further changing their properties. At present, such complexes show good application prospects in the fields of optoelectronic materials, adsorption and separation, catalysis, etc.

[0031] The present application uses pyrazole cyclotriade silver (I) complexes as crystallization partners for the organic molecules to be tested, and applies their π-acid···base supramolecular interactions to the structure identification of the organic molecules to be tested.

[0032] The pyrazole cyclotriade silver (I) complexes are specifically 3-substituted and / or 5-substituted pyrazole cyclotriade silver (I) complexes, which are 3-trifluoromethyl pyrazole cyclotriade silver (I) complex, 3-trifluoromethyl-5-methyl pyrazole cyclotriade silver (I) complex, 3-trifluoromethyl-5-tert-butyl pyrazole cyclotriade silver (I) complex, 3-trifluoromethyl-5-phenyl pyrazole cyclotriade silver (I) complex, 3,5-bistrifluoromethyl pyrazole cyclotriade silver (I) complex and 3,5-bisnitro pyrazole cyclotriade silver (I) complex. Among them, the preferred pyrazole cyclotriade silver (I) complex is 3,5-bistrifluoromethyl pyrazole cyclotriade silver (I) complex, the chemical formula of which is Ag3[3,5-(CF3)2Pz]3, and it is named as Ag3Pz3. It is a highly fluorinated, strong π-acid, and metal-organic complex with a planar stable three-metal coordination nine-membered ring. The above chemical structure is as follows:

[0033]

[0034] The Ag3Pz3 has good stability, solubility and crystallinity.

[0035] Ag3Pz3 can form crystal aggregates with different test organic molecules through various non-covalent interactions (such as π-acid···base interaction, C-H···F interaction, etc.), and through this strategy, it can promote the formation of co-crystals of difficult-to-crystallize test organic molecules. The crystal structure of the co-crystal contains both the pyrazole ring trinuclear silver (I) complex and the test organic molecule, so the pyrazole ring trinuclear silver (I) complex can be used as a crystallization partner of the test organic molecule, and then the chemical structure and stereoconfiguration of the organic molecule can be determined by single crystal diffraction.

[0036] The present application provides a method for determining the structure of an organic molecule, which is suitable for determining the structure of non-crystalline compounds, multi-chiral complex compounds and mixture samples, and specifically includes the following steps taking Ag3Pz3 as an example:

[0037] Step one, preparing Ag3Pz3 and performing single crystal X-ray diffraction analysis on the Ag3Pz3 crystal.

[0038] In some preferred embodiments of the present application, Ag3Pz3 is synthesized by using 3,5-bistrifluoromethylpyrazole and silver oxide, specifically as follows:

[0039] Silver oxide (Ag2O) and 3,5-bistrifluoromethylpyrazole ([3,5-(CF3)2Pz]H) with a molar ratio of 1:5 to 5:1 are mixed and dissolved in 10 to 50 mL of an ether solution. The mixed solution is placed in a light-proof condition and heated to reflux and then cooled, and the insoluble substances are removed by a silica gel column. The solvent is recovered by vacuum pumping under reduced pressure to obtain a white powder. The white powder is dissolved again and a colorless crystal is obtained by solvent evaporation at room temperature. The crystal is collected and washed, and then dried at 100°C to a constant weight to obtain high-purity Ag3Pz3.

[0040] Step two, mixing Ag3Pz3 prepared in step one and a test organic molecule sample to obtain a co-crystal of Ag3Pz3 and the test organic molecule. The co-crystal is collected and subjected to single crystal diffraction analysis.

[0041] The test sample is selected from one of an organic molecule monomer, a mixture of organic molecules or a natural extract. The organic molecule monomer is selected from one of an alcohol, an aldehyde, a ketone, an ether, an ester, an amine, a nitrogen oxide and a sulfide. The test sample includes volatile oils of natural origin, phenylpropanoids, flavonoids, anthraquinones, terpenes, alkaloids and steroidal compounds, etc.

[0042] In some embodiments of the present application, the crystallization partner Ag3Pz3 and the sample to be tested are dissolved in an organic solvent in a molar ratio of 1:10-10:1, shaken and filtered to obtain a clear mixed solution; and the co-crystals of Ag3Pz3 and the organic molecule to be tested are cultured under light-proof conditions. As a preferred embodiment of the present application, the molar ratio of the crystallization partner Ag3Pz3 and the sample to be tested is 1:2, 2:1 or 5:1, more preferably equimolar.

[0043] As a preferred embodiment of the present application, the organic solvent is selected from one or more of methanol, ethanol, acetonitrile, dichloromethane, trichloromethane, cyclohexane, petroleum ether, acetone, diethyl ether, benzene, ethyl acetate, toluene, isopropanol, 1,4-dioxane.

[0044] In some embodiments of the present application, to obtain co-crystals, one of solvent evaporation method, solvent diffusion method, vapor diffusion method, and solvothermal method can be used.

[0045] As a preferred embodiment of the present application, the co-crystal culture temperature of Ag3Pz3 and the organic molecule to be tested is -25℃-150℃.

[0046] Step three, the crystal structure is analyzed according to the diffraction data of the co-crystals, thereby obtaining the chemical structure and stereoconfiguration of the organic molecule to be tested.

[0047] In some embodiments of the present application, the Rigaku single crystal diffractometer is used to perform single crystal diffraction analysis on Ag3Pz3 in step one and the co-crystals in step two, and the diffraction data of both are collected. The light source is Cu Kα target radiation at The temperature for collecting single crystal diffraction data is -173℃-room temperature.

[0048] The collected diffraction data is analyzed by SHELXTL 6.10 program package and Olex2 1.2 software, the positions of some non-hydrogen atoms are determined by direct method (direct-methods), and then the coordinates of all non-hydrogen atoms are obtained by difference fourier map and full-matrix least-square method.

[0049] After obtaining the coordinates of all non-hydrogen atoms, the atomic species and structure refinement are further identified, and the coordinates of all hydrogen atoms are obtained by theoretical hydrogenation.

[0050] Example 1

[0051] The aforementioned cyclotri nuclear silver (I) complex Ag3Pz3 is used as a crystallization partner to determine the molecular structure of trans-anethol.

[0052] Anethole is a natural volatile oil with phenylpropanoid structure, which is liquid at room temperature (melting point: 20-21 °C) and has the chemical structure shown in Formula VII:

[0053]

[0054] S1. Preparation of Ag3Pz3 and single crystal X-ray diffraction analysis of Ag3Pz3 crystal.

[0055] S1.1. 43.2 mg of silver oxide (Ag2O) and 20.4 mg of 3,5-bistrifluoromethylpyrazole ([3,5-(CF3)2Pz]H) were mixed and dissolved in 20-30 mL of diethyl ether solution. The mixed solution was heated under reflux for 6 h in the dark, and after cooling, insoluble matter was removed by a silica gel column, and the solvent was recovered by vacuum pumping under reduced pressure to obtain 85.1 mg of white powder (yield: 91.2%). The white powder was dissolved in cyclohexane, and colorless crystals were obtained by solvent evaporation at room temperature. The crystals were collected and washed, and then dried at 100 °C to constant weight to obtain high-purity Ag3Pz3.

[0056] S1.2. The well-crystallized and appropriately sized Ag3Pz3 crystals obtained in S1.1 were selected for single crystal X-ray diffraction analysis. The obtained crystal belongs to the monoclinic system, and has the following crystal cell parameters: a = 90°, β = 97.1576(6)°, γ = 90°, The obtained crystal structure of Ag3Pz3 is shown in Figure 1 .

[0057] S2. Ag3Pz3 obtained in S1.2 and a sample of an organic molecule to be tested were mixed to obtain a co-crystal of Ag3Pz3 and the organic molecule to be tested. The co-crystal was collected and subjected to single crystal diffraction.

[0058] S2.1. 0.5 mg of anethole was dissolved in 1 mL of dichloromethane, and then 4 times the molar amount of high-purity Ag3Pz3 obtained in S1.2 was added. The mixed solution was filtered and then transferred to a capped glass vial (volume: 1.5 mL). A needle tube was inserted into the top of the glass vial to control the evaporation rate of the solvent. The glass vial was placed in the dark at room temperature and subjected to slow solvent evaporation. When the solvent was completely evaporated (about 2-3 days), colorless plate-shaped crystals appeared at the bottom of the vial.

[0059] S2.2. The well-crystallized and appropriately sized crystals obtained in step S2.1, which had different crystal cell parameters from Ag3Pz3, were selected for single crystal X-ray diffraction analysis to obtain the co-crystal Ag3Pz3·trans-anethol. The complete diffraction data of the co-crystal were collected. The obtained crystal belongs to the orthorhombic system, and has the following crystal cell parameters: α = 90°, β = 90°, γ = 90°,

[0060] S1.2. The instrument used for single crystal diffraction of S2.2 was also a Rigaku single crystal diffractometer, with Cu Kα target radiation at 1.5418 A, and the single crystal data collection temperature was 100 K.

[0061] S3. Based on the diffraction data of both Ag3Pz3 and the eutectic, the crystal structures of both were solved, and the chemical structure of the organic molecule under test was obtained.

[0062] The diffraction data collected in S1.2 and S2.2 were solved using the SHELXTL 6.10 package and Olex2 1.2 software, using direct-methods to determine the positions of some of the non-hydrogen atoms, and then using difference fourier maps and full-matrix least-square methods to obtain the coordinates of all non-hydrogen atoms. The atom types were further assigned and the structure refined, and the coordinates of all hydrogen atoms were obtained using the method of theoretical hydrogen addition. The crystal structure of the liquid molecule trans-anethol was thus solved.

[0063] The crystal structure of Ag3Pz3·trans-anethol is shown in Figure 2 , and the crystallographic data and some parameters of the structure refinement are shown in Table 1.

[0064] Table 1. Crystallographic data of Ag3Pz3·trans-anethol

[0065]

[0066]

[0067] Example 2

[0068] The molecular structure of chrysophanol was determined using the aforementioned cyclotri nuclear silver (I) complex Ag3Pz3 as a crystallization partner.

[0069] Chrysophanol is an anthraquinone compound, containing carbonyl, hydroxyl, benzene and other functional groups in its structure, and its chemical structure is shown in formula VIII:

[0070]

[0071]

[0072] ​S1. Preparation of Ag3Pz3 and single crystal X-ray diffraction analysis of Ag3Pz3 crystal.

[0073] High purity Ag3Pz3 was prepared by the same method as in Example 1.

[0074] S2. Ag3Pz3 prepared in S1.2 and the sample of the organic molecule to be tested were mixed to obtain a co-crystal of Ag3Pz3 and the organic molecule to be tested. The co-crystal was collected and subjected to single crystal diffraction.

[0075] S2.1. 0.6 mg of chrysophanol was dissolved in 1 mL of dichloromethane-ethanol mixed solution (volume ratio 1:3), followed by the addition of 2 times molar amount of high purity Ag3Pz3 obtained in S1. The mixed solution was filtered and then transferred to a capped glass vial (volume: 1.5 mL). A needle tube was inserted into the top of the glass vial to control the solvent evaporation rate. The glass vial was placed in a dark room at room temperature for slow solvent evaporation. When the solvent was completely evaporated (about 2-3 days), yellow flaky crystals appeared at the bottom of the vial.

[0076] S2.2. The crystals with good crystal faces, suitable size, and different cell parameters from Ag3Pz3 in S2.1 were selected for single crystal X-ray diffraction analysis to obtain the co-crystal Ag3Pz3 chrysophanol. The prepared crystal belongs to the orthorhombic system with space group Pbca and cell parameters of: α = 90°, β = 90°, γ = 90°,

[0077] The crystal structure of chrysophanol was resolved by the same method as S3 in Example 1.

[0078] The crystal structure of Ag3Pz3 chrysophanol is shown in Figure 3 , and part of the crystallographic diffraction data and structure refinement parameters are shown in Table 2.

[0079] Table 2. Crystallographic data of Ag3Pz3 chrysophanol

[0080]

[0081]

[0082] Example 3

[0083] The molecular structure of 7-hydroxy-5-methoxy-6,8-dimethylflavanone was determined using the aforementioned cyclotri nuclear silver (I) complex Ag3Pz3 as a crystallization partner.

[0084] 7-Hydroxy-5-methoxy-6,8-dimethylflavanone is a dihydroflavonoid compound containing functional groups such as carbonyl, hydroxyl, ether, and benzene groups. Its chemical structure is shown in Formula IX.

[0085]

[0086] S1. Prepare Ag3Pz3 and perform single-crystal X-ray diffraction analysis on Ag3Pz3 crystal.

[0087] High-purity Ag3Pz3 was prepared using the same method as in Example 1.

[0088] S2. Mix the Ag3Pz3 prepared in S1.2 with the organic molecule sample to be tested to obtain a eutectic of Ag3Pz3 and the organic molecule to be tested. Collect the eutectic and perform single-crystal diffraction.

[0089] S2.1. Weigh 0.7 mg of 7-hydroxy-5-methoxy-6,8-dimethylflavanone and dissolve it in 1 mL of a dichloromethane-acetone mixture (volume ratio 4:1). Then add an equimolar amount of the high-purity Ag3Pz3 obtained in S1. Filter the mixture and transfer it to a capped glass vial (volume: 1.5 mL). Insert a syringe into the top of the vial to control the solvent evaporation rate. Place the vial in the dark at room temperature for slow solvent evaporation. When the solvent has completely evaporated (approximately 2–3 days), pale yellow granular crystals will appear at the bottom of the vial.

[0090] S2.2. Select crystals from S2.1 with well-defined and appropriately sized crystal faces, and whose cell parameters differ from Ag3Pz3, and perform single-crystal X-ray diffraction analysis to obtain the eutectic Ag3Pz3-7-hydroxy-5-methoxy-6,8-dimethylflavanone. The obtained crystals belong to the triclinic crystal system, with space group [missing information]. The unit cell parameters are: α=107.384(3)°, β=102.336(2)°, γ=90.912(2)°,

[0091] The crystal structure of 7-hydroxy-5-methoxy-6,8-dimethylflavanone was determined using the same method as in S3 of Example 1.

[0092] The crystal structure of Ag3Pz3-7-hydroxy-5-methoxy-6,8-dimethylflavanone is shown below.Figure 4 Part of the crystallographic diffraction data and structure refinement parameters of Ag3Pz3 are shown in Table 3.

[0093] Table 3. Crystallographic data of Ag3Pz3 5-hydroxy-5-methoxy-6,8-dimethylflavanone

[0094]

[0095] Example 4

[0096] The molecular structure of ammothamnine was determined using the aforementioned silver(I) complex Ag3Pz3 as a crystallization partner.

[0097] Ammothamnine is an alkaloid compound with a tetracyclic structure, containing functional groups such as carbonyl, nitroxy, etc., and has four chiral centers. The chemical structure is shown in Formula X:

[0098]

[0099] S1. Preparation of Ag3Pz3 and single crystal X-ray diffraction analysis of Ag3Pz3 crystals.

[0100] High-purity Ag3Pz3 was prepared using the same method as in Example 1.

[0101] S2. Mixing Ag3Pz3 prepared in S1.2 and the sample of the organic molecule to be tested to obtain a co-crystal of Ag3Pz3 and the organic molecule to be tested. Collect the co-crystal and perform single crystal diffraction.

[0102] S2.1. 0.5 mg of ammothamnine sample was dissolved in 1 mL of a mixture of chloroform-acetonitrile (volume ratio 1:2), and then an equimolar amount of high-purity Ag3Pz3 obtained in S1 was added. The mixed solution was filtered and then transferred to a capped glass vial (volume: 1.5 mL). A needle tube was inserted into the top of the glass vial to control the solvent evaporation rate. The glass vial was placed in a light-proof condition at room temperature for slow solvent evaporation. When the solvent was completely evaporated (about 2-3 days), colorless block crystals appeared at the bottom of the vial.

[0103] S2.2. Selecting crystals with good crystal faces, suitable size, and different cell parameters from Ag3Pz3 in S2.1 for single crystal X-ray diffraction analysis to obtain a co-crystal Ag3Pz3·ammothamnine. The prepared crystal belongs to monoclinic system with space group P21, and the cell parameters are: a = 90°, β = 112.500(2)°, γ = 90°,

[0104] The crystal structure of oxymatrine was solved using the same method as S3 in Example 1. Based on the Flack parameter of the crystal [-0.013(6)], the absolute configuration of oxymatrine was determined.

[0105] The crystal structure of Ag3Pz3·ammothamnine is shown in Figure 5 and partial parameters of crystallographic diffraction data collection and structure refinement are shown in Table 4.

[0106] Table 4. Crystallographic data of Ag3Pz3·ammothamnine

[0107]

[0108] Example 5

[0109] The molecular structure of santonin was determined using the aforementioned cyclotri nuclear silver (I) complex Ag3Pz3 as a crystallization partner.

[0110] Santonin is a natural terpenoid anthelmintic with a 6 / 6 / 5 tricyclic structure, containing double bond, α, β-unsaturated ketone and ester functional groups, with four chiral centers, and its chemical structure is shown in Formula XI:

[0111]

[0112] S1. Preparation of Ag3Pz3 and single crystal X-ray diffraction analysis of Ag3Pz3 crystals.

[0113] High-purity Ag3Pz3 was prepared using the same method as in Example 1.

[0114] S2. Mixing Ag3Pz3 prepared in S1.2 and the sample of the organic molecule to be tested to obtain a co-crystal of Ag3Pz3 and the organic molecule to be tested. Collecting the co-crystal and performing single crystal diffraction.

[0115] S2.1. 0.6 mg of santonin was dissolved in 1.5 mL of a cyclohexane-dichloromethane solution (volume ratio 1:2), followed by the addition of an equimolar amount of high-purity Ag3Pz3 obtained in (a). The mixed solution was filtered and then transferred to a capped glass vial (volume: 1.5 mL). A needle tube was inserted into the top of the glass vial to control the solvent evaporation rate. The glass vial was placed in a light-proof condition at room temperature for slow solvent evaporation. When the solvent was completely evaporated (about 2-3 days), colorless block crystals appeared at the bottom of the vial.

[0116] S2.2. The crystal with good crystal face, suitable size and different cell parameters from Ag3Pz3 in S2.1 is selected for single crystal X-ray diffraction analysis to obtain the eutectic Ag3Pz3santonin. The prepared crystal belongs to the orthorhombic system, the space group is P212121, and the cell parameters are: a = 90°, β = 90°, γ = 90°,

[0117] The crystal structure of santonin is analyzed by the same method as S3 in Example 1. Based on the Flack parameter [-0.026(5)] of the crystal, the absolute configuration of the santonin molecule can be determined. The crystal structure of Ag3Pz3santonin is shown in Figure 6 , and part of the crystallographic diffraction data and structure refinement parameters are shown in Table 5.

[0118] Table 5. Crystallographic data of Ag3Pz3santonin

[0119]

[0120] Example 6

[0121] The molecular structure of spironolactone is determined by using the aforementioned cyclotri nuclear silver (I) complex Ag3Pz3 as a crystallization partner.

[0122] Spironolactone is a natural diuretic, which has a 6 / 6 / 6 / 5 / 5 five-ring steroid nucleus, and contains carbonyl, lactone and sulfide functional groups in the structure, has 7 consecutive chiral centers, and the chemical structure is shown as formula XX:

[0123]

[0124] S1. Preparation of Ag3Pz3 and single crystal X-ray diffraction analysis of Ag3Pz3 crystal.

[0125] High-purity Ag3Pz3 is prepared by the same method as in Example 1.

[0126] S2. Ag3Pz3 prepared in S1.2 and the sample of the organic molecule to be tested are mixed to obtain the eutectic of Ag3Pz3 and the organic molecule to be tested. The eutectic is collected and subjected to single crystal diffraction.

[0127] S2.1. Weigh 1.0 mg of spironolactone and dissolve it in 1.5 mL of a cyclohexane-dichloromethane mixed solution (volume ratio 1:1), then add an equimolar amount of high-purity Ag3Pz3 obtained in (a). Filter the mixed solution, then transfer it to a capped glass vial (volume: 1.5 mL). Insert a syringe needle on top of the glass vial to control the solvent evaporation rate. Place the glass vial in a dark room at room temperature for slow solvent evaporation. When the solvent is completely evaporated (about 2-3 days), colorless needle-shaped crystals appear at the bottom of the vial.

[0128] S2.2. Select the crystals with good crystal faces, suitable size, and different cell parameters from Ag3Pz3 for single crystal X-ray diffraction analysis to obtain the eutectic Ag3Pz3spironolactone. The prepared crystal belongs to the monoclinic system, with a space group of P21, and a cell parameter of: a = 90°, β = 99.7340(10)°, γ = 90°,

[0129] The crystal structure of spironolactone is analyzed using the same method as S3 in Example 1. Based on the Flack parameter of the crystal [-0.024(13)], the absolute configuration of the spironolactone molecule can be determined.

[0130] The crystal structure of Ag3Pz3spironolactone is shown in Figure 7 , and part of the crystallographic diffraction data and structure refinement parameters are shown in Table 6.

[0131] Table 6. Crystallographic data of Ag3Pz3spironolactone

[0132]

[0133]

[0134] Example 7

[0135] Using the aforementioned cyclotri nuclear silver (I) complex Ag3Pz3 as a crystallization partner, the structure of a compound is identified directly from the extract of the medicinal plant water wenghua.

[0136] S1. Preparation of Ag3Pz3 and single crystal X-ray diffraction analysis of Ag3Pz3 crystals.

[0137] High-purity Ag3Pz3 is prepared using the same method as in Example 1.

[0138] S2. Mix Ag3Pz3 prepared in S1.2 and water wenghua extract to obtain a eutectic of Ag3Pz3 and the organic molecule to be tested. Collect the eutectic and perform single crystal diffraction.

[0139] S2.1. 50 g of naturally dried Cleistocalyx operculatus (Roxb.) Merr. & Perry flowers were pulverized into coarse powder and extracted with methanol under ultrasonication at room temperature for 3 times, 60 min each time. The combined extract was concentrated under reduced pressure to obtain 4.1 g of total extract. The total extract was dissolved in methanol and loaded onto an ODS solid phase extraction (SPE) column to remove insoluble materials and pigments, plant waxes, etc. The effluent of the extraction column was concentrated under reduced pressure with a vacuum pump to obtain 3.8 g of pretreated Cleistocalyx operculatus flower extract.

[0140] 130 mg of high-purity Ag3Pz3 obtained in S1 was dissolved in a dichloromethane-methanol mixed solution (volume ratio 2:1), followed by the addition of 13 mg of Cleistocalyx operculatus flower extract. The mixed solution was filtered and then transferred to a capped glass vial (volume: 24 mL). A needle tube was inserted into the top of the glass vial to control the solvent evaporation rate. The glass vial was placed in a light-proof condition at room temperature for slow solvent evaporation. When the solvent was completely evaporated (about 6-7 days), a large amount of crystals appeared at the bottom of the vial.

[0141] S2.2. Crystals with good crystal faces, suitable size, and different cell parameters from Ag3Pz3 obtained in S2.1 were selected for single crystal X-ray diffraction analysis, obtaining four eutectics Ag3Pz3·1, Ag3Pz3·2, Ag3Pz3·3, and Ag3Pz3·4·5.

[0142] The crystal structures of the four eutectics Ag3Pz3·1-Ag3Pz3·4·5 were resolved using the same method as S3 in Example 1.

[0143] The crystal structures of Ag3Pz3·1-Ag3Pz3·4·5 are shown in Figure 8 -11, the crystallographic diffraction data and part of the parameters of the structure refinement are shown in Table 7 and Table 8.

[0144] Table 7. Crystallographic data of Ag3Pz3·1 and Ag3Pz3·2

[0145]

[0146]

[0147] Table 8. Crystallographic data of Ag3Pz3·3 and Ag3Pz3·4·5

[0148]

[0149] The mixed sample or natural extract usually contains multiple organic molecules. For the structural identification of the organic molecules in the mixed sample or natural extract, the organic compounds are usually separated by using silica gel, macroporous resin, high performance liquid chromatography and other chromatographic methods to obtain each compound monomer. Then, for each compound monomer, infrared, ultraviolet, mass spectrometry, nuclear magnetic resonance and other spectroscopic techniques are used to analyze the compound structure.

[0150] However, by using the method of the present application, the chemical structures of five compounds, i.e. 6-formyl-7-hydroxy-5-methoxy-8-methylflavanone (1), desmosflavanone II (2), 3'-formyl-4',6'-dihydroxy-2'-methoxy-5'-methylchalcone (3), 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (4) and 4',6'-dihydroxy-3'-(methoxymethyl)-2'-methoxy-5'-methylchalcone (5), can be directly identified from the extract of the water onion flower without going through the cumbersome chromatographic separation and spectroscopic analysis process, and the chemical structures of the five compounds are as follows:

[0151]

[0152] The above is only an embodiment of the present application and is not used to limit the present application. Any modification, equivalent replacement, improvement and the like made within the spirit and principle of the present application are included in the scope of the claims of the present application.

Claims

1. A method for determining the structure of organic molecules, characterized in that, Application of pyrazole ring trinuclear silver (I) complexes in the determination of organic molecular structures; the pyrazole ring trinuclear silver (I) complex is a 3,5-bis(trifluoromethyl)pyrazole ring trinuclear silver (I) complex with the chemical formula Ag3[3,5-(CF3)2Pz]3, and its structure is shown in Formula I: Specifically, the following steps are included: The pyrazole cyclic trinuclear silver (I) complex is mixed with the sample to be tested, which is an amorphous compound, a multi-chiral complex compound, an organic molecule in a natural extract, or an organic molecule containing only CHON light elements. A co-crystal of the pyrazole cyclic trinuclear silver (I) complex and the organic molecule in the sample to be tested is obtained, and the co-crystal is subjected to single crystal diffraction analysis to obtain the crystal diffraction data of the co-crystal. Based on the crystal diffraction data of the eutectic, the crystal structure is analyzed, thereby obtaining the chemical structure and stereoconfiguration of the organic molecule to be tested.

2. The method for determining the structure of organic molecules according to claim 1, characterized in that: The pyrazole ring trinuclear silver (I) complex is a pyrazole ring trinuclear silver (I) complex with 3- and / or 5-position substitution.

3. The method for determining the structure of organic molecules according to claim 1, characterized in that, The process of analyzing the crystal structure based on the diffraction data of the eutectic crystal specifically includes the following steps: The positions of some non-hydrogen atoms were determined using a direct method, and then the coordinates of all non-hydrogen atoms were obtained using the difference function method and the least squares method. After obtaining the coordinates of all non-hydrogen atoms, the types and structures of atoms are further identified and refined, and the coordinates of all hydrogen atoms are obtained using the theoretical hydrogenation method.

4. The method for determining the structure of organic molecules according to claim 1, characterized in that: After mixing the pyrazole-ringed trinuclear silver (I) complex with the test sample in an organic solvent, the co-crystal of the pyrazole-ringed trinuclear silver (I) complex and the test organic molecule was cultured under light-protected conditions; the temperature of the co-crystal culture was −25°C to 150°C.

5. The method for determining the structure of organic molecules according to claim 4, characterized in that: The molar ratio of the pyrazole ring trinuclear silver (I) complex to the test sample is 1:10 to 10:

1.

6. The method for determining the structure of organic molecules according to claim 5, characterized in that: The organic solvent is one or more of methanol, ethanol, acetonitrile, dichloromethane, chloroform, cyclohexane, petroleum ether, acetone, diethyl ether, benzene, ethyl acetate, toluene, isopropanol, and 1,4-dioxane.

7. The method for determining the structure of organic molecules according to claim 1, characterized in that: The temperature for the single-crystal diffraction analysis was −173°C to room temperature.

8. The method for determining the structure of organic molecules according to claim 1, characterized in that: The eutectic is obtained by one of the following methods: solvent evaporation, solvent diffusion, gas phase diffusion, or solvothermal method.

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