A method for determining the absolute structure of chiral organic crystals by electron diffraction and its application

Abstract

The present invention relates to a method for determining the absolute structure of chiral organic crystals by electron diffraction and its application, comprising the following steps: obtaining a positive zone axis selected area electron diffraction pattern, an off-positive zone axis selected area electron diffraction pattern, a software simulated electron diffraction pattern, and a dynamical simulated electron diffraction pattern intensity map; superimposing the positive zone axis selected area electron diffraction pattern and the off-positive zone axis selected area electron diffraction pattern to obtain an experimental reconstructed electron diffraction pattern; comparing the software simulated electron diffraction pattern and the experimental reconstructed electron diffraction pattern to determine the absolute direction of the experimental reconstructed electron diffraction pattern of the crystal to be measured; extracting the integrated intensity of the electron diffraction spots in the positive zone axis selected area electron diffraction pattern to obtain an experimental electron diffraction pattern intensity map; respectively comparing the matching degrees of the dynamical simulated electron diffraction pattern intensity map and the experimental electron diffraction pattern intensity map to determine the absolute configuration of the molecules of the crystal to be measured. It overcomes the problem of the uncertainty of the zone axis direction of a single selected area electron diffraction.

Description

Technical Field

[0001] The present invention relates to the field of experimental chemistry, and particularly to a method for determining the absolute structure of chiral organic crystals by electron diffraction and its applications. Background Art

[0002] Chirality is very common in organic molecules and organic materials, and chirality is closely related to the properties of substances. Especially for chiral drugs, enantiomers often exhibit completely different pharmacological activities. Usually, single-crystal X-ray is used to directly characterize the crystal structure and absolute configuration of chiral organic molecules. However, due to instrument limitations, it is generally only applicable to crystals larger than ten micrometers. Electron diffraction is an effective means for characterizing nanocrystals. However, it is still relatively difficult to determine the absolute structure. Lukas et al. reported determining the absolute structure of chiral organic crystals by electron diffraction dynamical refinement. However, when collecting data, the method deviates from the zone axis, and the dynamical effect of electron diffraction is weakened. Recently, the crystal structure analysis of three-dimensional electron diffraction by cryo-electron microscopy combined with the eutectic method has also been used to determine the absolute structure of organic molecules. However, this method requires the target molecule to form a suitable co-crystal with a molecule of known structure. Therefore, it is very necessary to provide a method for judging the chiral structure of organic nanocrystals. Summary of the Invention

[0003] Aiming at the problems existing in the prior art, the present invention provides a simple method for confirming the chirality of crystals by selected area electron diffraction, which does not require growing co-crystals and can visually confirm the chiral structure of organic nanocrystals, especially for samples with small crystal sizes that cannot be analyzed by single-crystal X-ray diffraction.

[0004] The present invention provides a method for determining the absolute structure of chiral organic crystals by electron diffraction, comprising the following steps:

[0005] (1) Obtain the zone axis selected area electron diffraction pattern A of the crystal to be measured, the off-zone axis selected area electron diffraction pattern B, the software-simulated electron diffraction pattern C, and the dynamical simulation electron diffraction pattern intensity diagrams D1 and D2;

[0006] (2) Superimpose the zone axis selected electron diffraction pattern A and the off-zone axis selected electron diffraction pattern B in step (1) to obtain an experimental reconstructed electron diffraction pattern E;

[0007] (3) Compare the software-simulated electron diffraction pattern C obtained in step (1) with the experimental reconstructed electron diffraction pattern E obtained in step (2), and rotate the direction of the experimental reconstructed electron diffraction pattern E so that the direction of the experimental reconstructed electron diffraction pattern E is consistent with the direction of the software-simulated electron diffraction pattern C, thereby determining the absolute direction of the experimental reconstructed electron diffraction pattern E of the crystal to be measured;

[0008] (4) In the extraction step, select the integrated intensity of the electron diffraction spots in the electron diffraction pattern A of the positive zone axis described in step (1), and input this intensity information into E in the experimentally reconstructed electron diffraction pattern obtained in step (2) to obtain the experimental electron diffraction pattern intensity map F;

[0009] (5) Compare the matching degrees of the kinetic simulation electron diffraction pattern intensity maps D1 and D2 described in step (1) and the experimental electron diffraction pattern intensity map F described in step (4) respectively, so as to determine the absolute configuration of the crystal to be measured.

[0010] Preferably, in step (1), the positive zone axis selects the electron diffraction pattern A including the zero-order diffraction spot.

[0011] Preferably, in step (1), the off-positive zone axis selects the electron diffraction pattern B including the zero-order diffraction spot and the first-order diffraction spot.

[0012] Preferably, in step (1), when obtaining the off-positive zone axis selected electron diffraction pattern A, the angle by which the crystal to be measured rotates off the positive zone axis is 0-5°.

[0013] Preferably, in step (1), the method for obtaining the kinetic simulation electron diffraction pattern intensity map D is: the Bloch-wave method in the crystallographic software JEMS.

[0014] Preferably, in step (1), the kinetic simulation electron diffraction pattern intensity maps D1 and D2 are the kinetic simulation electron diffraction pattern intensity maps of two enantiomers.

[0015] Preferably, in step (1), the tool for software-simulating the electron diffraction pattern C is: the crystallographic software JEMS.

[0016] Preferably, in step (4), the tool for obtaining the integrated intensity is: the electron diffraction pattern processing software EDprocess.

[0017] Preferably, in step (5), the method for judging the matching degree is: compare the diffraction pairs with central symmetry in the experimental electron diffraction pattern intensity map F with the corresponding diffraction pairs with central symmetry in the two kinetic simulation electron diffraction pattern intensity maps D1 and D2 respectively.

[0018] If the same rate of the intensity relationship of the diffraction pairs in the kinetic simulation electron diffraction pattern intensity map D1 and the experimental electron diffraction pattern intensity map F > 50%, then the structure of the crystal to be measured is consistent with the absolute structure of the kinetic simulation electron diffraction pattern intensity map D1.

[0019] If the rate of the same intensity relationship of diffraction pairs between the kinetic simulation electron diffraction pattern intensity map D2 and the experimental electron diffraction pattern intensity map F is > 50%, the structure of the crystal to be measured is consistent with the absolute structure of the kinetic simulation electron diffraction pattern intensity map D2.

[0020] The second aspect of the present invention provides an application of the above method for determining the absolute structure of chiral organic crystals using electron diffraction in determining the absolute structure of nanocrystals.

[0021] The present invention has at least one of the following beneficial effects:

[0022] 1) The present invention provides a simple and effective scheme for confirming the chirality of crystals using positive zone axis selected area electron diffraction, solving the problem of determining the left and right chirality of organic nanocrystals. Overcoming the problem of the uncertainty of the zone axis direction in a single selected area electron diffraction, the experimental reconstructed electron diffraction pattern E is determined, and the absolute structure of the crystal to be measured is obtained.

[0023] 2) Compared with using single crystal X-ray diffraction to determine crystal chirality, electron diffraction makes it possible to characterize the chirality of nanoscale crystals. In addition, in the present invention, only two selected area electron diffraction patterns are required, without additional data collection strategies, which is very friendly for the characterization of electron beam sensitive materials (such as organic crystals). Description of the Drawings

[0024] Figure 1 It is a flowchart of a method for determining the absolute structure of chiral organic crystals using electron diffraction in the present invention.

[0025] Figure 2 It is a flowchart of Example 1 in the present invention.

[0026] Figure 3 It is a schematic diagram of Example 1 in the present invention.

[0027] Figure 4 It is a schematic diagram of Example 2 in the present invention.

[0028] Figure 5 It is a diffraction pattern diagram of a crystal that does not apply the technical solution of the present invention.

[0029] Figure 6 It is a diffraction pattern diagram of a crystal that applies the technical solution of the present patent. Detailed Embodiments

[0030] The following uses specific specific examples to illustrate the implementation manners of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific implementation manners. Various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0031] It should be noted that the process equipment or devices not specifically noted in the following embodiments all adopt conventional equipment or devices in the art.

[0032] As Figure 1 shown, the present invention provides a method for determining the absolute structure of a chiral organic crystal by electron diffraction, including the following steps:

[0033] (1) Obtain the positive zone axis selected area electron diffraction pattern A of the crystal to be measured, the off-positive zone axis selected area electron diffraction pattern B, the software-simulated electron diffraction pattern C, and the kinematic-simulated electron diffraction pattern intensity diagrams D1 and D2;

[0034] (2) Superimpose the positive zone axis selected area electron diffraction pattern A and the off-positive zone axis selected area electron diffraction pattern B in step (1) to obtain an experimental reconstructed electron diffraction pattern E;

[0035] (3) Compare the software-simulated electron diffraction pattern C obtained in step (1) with the experimental reconstructed electron diffraction pattern E obtained in step (2), and rotate the direction of the experimental reconstructed electron diffraction pattern E so that the direction of the experimental reconstructed electron diffraction pattern E is consistent with the direction of the software-simulated electron diffraction pattern C, thereby determining the absolute direction of the experimental reconstructed electron diffraction pattern E of the crystal to be measured;

[0036] (4) Extract the integrated intensity of the electron diffraction points in the positive zone axis selected area electron diffraction pattern A described in step (1), and input this intensity information into the experimental reconstructed electron diffraction pattern E obtained in step (2) to obtain an experimental electron diffraction pattern intensity diagram F;

[0037] (5) Compare the matching degrees of the kinematic-simulated electron diffraction pattern intensity diagrams D1 and D2 described in step (1) and the experimental electron diffraction pattern intensity diagram F described in step (4) respectively, thereby determining the absolute configuration of the crystal to be measured.

[0038] The zone axis is the cross product of two diffraction spot vectors and conforms to the right-hand rule. The diffraction spots represent the reciprocal lattice corresponding to the crystal plane. In the direct lattice, all crystal planes parallel to a certain crystal direction [uvw] at the same time form a zone, and this crystal direction is called the zone axis. Therefore, the zone axis can be determined by taking the cross product with the plane normal. The positive zone axis direction refers to along a certain zone axis direction.

[0039] Selected area electron diffraction is a method of performing electron diffraction on a micro-region of interest in a crystal to be measured to obtain an electron diffraction pattern of that range. It is achieved by moving the selected area aperture placed in the image plane of the objective lens to enclose the region of interest and then performing imaging operations or diffraction operations separately to realize the morphological analysis and structural analysis of the selected region.

[0040] The positive zone axis selected area electron diffraction pattern is the selected area electron diffraction pattern of a nanocrystal taken along the positive zone axis direction. By rotating the crystal to be measured by a certain angle away from the positive zone axis for shooting, a selected area electron diffraction pattern deviating from the positive zone axis containing higher-order diffraction spots can be obtained. Among them, the angle by which the crystal to be measured rotates away from the positive zone axis is 0 - 5°. The positive zone axis selected area electron diffraction pattern obtained includes zero-order diffraction spots, and the selected area electron diffraction pattern deviating from the zone axis includes zero-order diffraction spots and first-order diffraction spots.

[0041] The software-simulated electron diffraction pattern C contains the zero-order and first-order diffraction patterns in this direction. The simulation is based on Bragg's law and requires prior knowledge of the crystallographic cif file. For the selected area electron diffraction pattern in any direction, the diffraction lattice hkl in the diffraction pattern in the [uvw] direction should satisfy the diffraction law, that is, hu + kv + lw = N. When N = 0, the zero-order diffraction spectrum in this direction is obtained, and when N = 1, the first-order diffraction spectrum in this direction is obtained (u, v, w, h, k, l are all integers). Considering the geometric relationship of electron diffraction, the first-order diffraction spectrum can be superimposed on the zero-order diffraction spectrum to form a simulated diffraction pattern that simultaneously has first-order diffraction spots and zero-order diffraction spots. Affected by the zone axis direction and the crystal's own structure, the positions of the first-order diffraction spots and the zero-order diffraction spots do not coincide. This simulation process can be realized through crystallographic software such as JEMS.

[0042] Chirality means an asymmetric distribution of the electric potential inside the crystal. In electron diffraction, affected by the dynamical effect, in the selected area electron diffraction pattern, two diffraction spots (Friedel pairs, hkl and -h -k -l) that are centrosymmetric with respect to the transmission spot center will show a strong diffraction spot and a relatively weak diffraction spot in intensity. In the selected area electron diffraction pattern of a non-chiral crystal, a pair of diffraction spots (Friedel pairs) that are centrosymmetric with respect to the transmission spot center always satisfy Friedel's rule, and the intensities of the Friedel pairs are equal, that is, I hkl = I -h-k-l ; for chiral crystals, considering the influence of the dynamical effect of electron diffraction, Friedel's rule is broken, and unequal intensities of the Friedel pairs will be obtained, that is, I hkl ≠ I -h-k-lThe kinetic simulation electron diffraction pattern intensity diagrams D1 and D2 can simulate the intensity relationship of diffraction points. The kinetic simulation electron diffraction pattern intensity diagrams D1 and D2 are simulation methods closer to the actual sample situation and can be used for quantitative intensity simulation of multi-beam diffraction. The kinetic simulation process in this solution uses the Bloch-wave method provided by the crystallography software JEMS. The kinetic simulation electron diffraction pattern intensity diagrams D1 and D2 include the kinetic simulation electron diffraction pattern intensity diagrams of two corresponding isomers.

[0043] Affected by the uncertainty of the direction of a single selected area electron diffraction pattern, it is impossible to distinguish the diffraction points hkl and -h-k-l and the diffraction directions [uvw] and [-u-v-w] in the diffraction pattern, that is, the diffraction lattice may be mislabeled. Therefore, confirming the absolute direction of this diffraction pattern can avoid this problem. The specific operation method is as follows: First, all the diffraction point position information (including first-order diffraction points and zero-order diffraction points) can be extracted from the electron diffraction pattern selected from the positive zone axis and the electron diffraction pattern selected away from the positive zone axis and merged into an experimental reconstructed electron diffraction pattern E (the diffraction point positions are extracted by ImageJ and redrawn using python). Among them, the diffraction points symmetric to the center of the transmission spot (Friedel pairs) are marked as strong black points and weak gray points. Then, it can be intuitively seen that the first-order diffraction points have a periodic position change relative to the zero-order diffraction points. By rotating, the relative positions of the first-order diffraction points and the zero-order diffraction points of the experimental reconstructed electron diffraction pattern E are made to exactly match the relative positions of the first-order diffraction point lattice and the zero-order diffraction point lattice of the software-simulated electron diffraction pattern C. At this time, only one direction can make the two completely consistent, and the absolute direction of this experimental reconstructed electron diffraction pattern is obtained.

[0044] In step (4), the integrated intensity of the electron diffraction points in the positive zone axis selected area electron diffraction pattern A refers to that in the actual experiment, the intensity distribution of the diffraction points should be close to a Gaussian distribution, that is, strong in the middle and weak around. Extracting the integrated intensity means considering the intensity of each pixel point in this diffraction point area range and summing them up. This part of the function can be implemented using the electron diffraction pattern processing software ED process.

[0045] In step (5), the method for judging the matching degree is as follows: the diffraction pairs with central symmetry in the experimental electron diffraction pattern intensity map F are respectively compared with the corresponding diffraction pairs with central symmetry in the two dynamic simulation electron diffraction pattern intensity maps D1 and D2. If the same rate of the intensity relationship of the diffraction pairs in the dynamic simulation electron diffraction pattern intensity map D1 and the experimental electron diffraction pattern intensity map F is > 50%, the structure of the crystal to be measured is consistent with the structure of the dynamic simulation electron diffraction pattern intensity map D1; if the same rate of the intensity relationship of the diffraction pairs in the dynamic simulation electron diffraction pattern intensity map D2 and the experimental electron diffraction pattern intensity map F is > 50%, the structure of the crystal to be measured is consistent with the structure of the dynamic simulation electron diffraction pattern intensity map D2.

[0046] Example 1

[0047] Cinchonine crystals belong to the monoclinic system. The specific steps for chiral characterization of cinchonine crystals are as follows:

[0048] As Figure 3 shown, (1) Obtain the positive zone axis selected area electron diffraction pattern A of cinchonine crystals, the off-positive zone axis selected area electron diffraction pattern B of cinchonine crystals, the software simulation electron diffraction pattern C of cinchonine crystals, the dynamic simulation electron diffraction pattern intensity map D1 of (+)-cinchonine crystals, and the dynamic simulation electron diffraction pattern intensity map D2 of (-)-cinchonine crystals;

[0049] (2) Superimpose the positive zone axis selected area electron diffraction pattern A and the off-positive zone axis selected area electron diffraction pattern B of cinchonine crystals in step (1) to obtain the experimental reconstructed electron diffraction pattern E of cinchonine crystals;

[0050] (3) Compare the software simulation electron diffraction pattern C of cinchonine crystals obtained in step (1) with the experimental reconstructed electron diffraction pattern E of cinchonine crystals obtained in step (2), and rotate the direction of the experimental reconstructed electron diffraction pattern E of cinchonine crystals to make the direction of the experimental reconstructed electron diffraction pattern E of cinchonine crystals consistent with the direction of the software simulation electron diffraction pattern C of cinchonine crystals, so as to determine the absolute direction of the experimental reconstructed electron diffraction pattern E of cinchonine crystals;

[0051] (4) Extract the integrated intensity of the electron diffraction points in the positive zone axis selected area electron diffraction pattern A of cinchonine crystals described in step (1), and input this intensity information into the experimental reconstructed electron diffraction pattern E of cinchonine crystals obtained in step (2) to obtain the experimental electron diffraction pattern intensity map F of cinchonine crystals;

[0052] (5) By comparing the experimental electron diffraction pattern intensity map F of the cinchonine crystal described in step (4) with the dynamic simulation electron diffraction pattern intensity map D1 of the (+)-cinchonine crystal and the dynamic simulation electron diffraction pattern intensity map D2 of the enantiomer of the (-)-cinchonine crystal respectively, it is found that among the 7 pairs of diffraction points with central symmetry in the experimental electron diffraction pattern intensity map F of the cinchonine crystal, the intensity relationships of 6 pairs of corresponding diffraction points are consistent with those in the dynamic simulation electron diffraction pattern intensity map D1 of the (+)-cinchonine crystal. The same rate of the diffraction pair intensity relationships between the experimental electron diffraction pattern intensity map F of the cinchonine crystal and the dynamic simulation electron diffraction pattern intensity map D1 of the (+)-cinchonine crystal is > 50%. Therefore, the structure of the crystal to be measured is consistent with the structure of the dynamic simulation electron diffraction pattern intensity map D1 of the (+)-cinchonine crystal, and the crystal to be measured is the (+)-cinchonine crystal.

[0053] Example 2

[0054] Cinchonidine is an isomer but not an enantiomer of cinchonine. This crystal belongs to the orthorhombic system. The steps for characterizing the chirality of the cinchonidine crystal are as follows:

[0055] As Figure 3 shown, (1) Obtain the positive zone axis selected area electron diffraction pattern A of the cinchonidine crystal, the off-positive zone axis selected area electron diffraction pattern B of the cinchonidine crystal, the software simulation electron diffraction pattern C of the cinchonidine crystal, the dynamic simulation electron diffraction pattern intensity map D1 of the (+)-cinchonidine crystal, and the dynamic simulation electron diffraction pattern intensity map D2 of the (-)-cinchonidine crystal;

[0056] (2) Superimpose the positive zone axis selected area electron diffraction pattern A and the off-positive zone axis selected area electron diffraction pattern B of the cinchonidine crystal in step (1) to obtain the experimental reconstructed electron diffraction pattern E of the cinchonidine crystal;

[0057] (3) Compare the software simulation electron diffraction pattern C of the cinchonidine crystal obtained in step (1) with the experimental reconstructed electron diffraction pattern E of the cinchonidine crystal obtained in step (2), and rotate the direction of the experimental reconstructed electron diffraction pattern E of the cinchonidine crystal so that the direction of the experimental reconstructed electron diffraction pattern E of the cinchonidine crystal is consistent with the direction of the software simulation electron diffraction pattern C of the cinchonidine crystal, thereby determining the absolute direction of the experimental reconstructed electron diffraction pattern E of the cinchonidine crystal;

[0058] (4) Extract the integrated intensity of the electron diffraction points in the positive zone axis selected area electron diffraction pattern A of the cinchonidine crystal described in step (1), and input this intensity information into the experimental reconstructed electron diffraction pattern E of the cinchonidine crystal obtained in step (2) to obtain the experimental electron diffraction pattern intensity map F of the cinchonidine crystal;

[0059] (5) By comparing the experimental electron diffraction pattern intensity map F described in step (4) with the dynamic simulation electron diffraction pattern intensity map D1 of the (+)-cinchonidine crystal and the dynamic simulation electron diffraction pattern intensity map D2 of the (-)-cinchonidine crystal respectively, it is found that among the 10 pairs of diffraction points with centrosymmetric diffraction points in the experimental electron diffraction pattern intensity map F of the cinchonidine crystal, a total of 8 pairs of corresponding diffraction point intensity relationships are consistent with the dynamic simulation electron diffraction pattern intensity map D1 of the (-)-cinchonidine. The same rate of the diffraction pair intensity relationship between the experimental electron diffraction pattern intensity map F of the crystal to be measured and the dynamic simulation electron diffraction pattern intensity map D2 of the (-)-cinchonidine is > 50%. Therefore, the structure of the crystal to be measured is consistent with the structure of the dynamic simulation electron diffraction pattern intensity map D2 of the (-)-cinchonidine, and the crystal to be measured is (-)-cinchonidine.

[0060] Example 3

[0061] To verify the feasibility of this technical solution, selected area electron diffraction pattern data of multiple cinchonine and cinchonidine crystals (with known chiral structures) along different directions were collected, and the final results all pointed to the correct absolute configuration of the molecule, as shown in Table 1:

[0062] Table 1 Selected area electron diffraction pattern data of cinchonine and cinchonidine crystals along different directions

[0063]

[0064] Example 4

[0065] As Figure 5 shown, for the monoclinic system, the

[101] direction and the [-10-1] direction are exactly the same, and these two diffraction patterns cannot be distinguished. Therefore, the technical solution in this patent is not applicable; while for the zone axis directions not in the table, such as Figure 6 shown, it can be seen that for the

[122] and [-1-2-2] directions of the monoclinic system, the diffraction patterns of the two directions are completely different, and the technical solution in this patent is still applicable. The zone axes not applicable to this invention are shown in Table 2:

[0066] Table 2 Zone axes not applicable to this invention

[0067]

[0068] The above embodiments only illustrate the principles and effects of the present invention by way of example, and are not used to limit the present invention. Any person familiar with this technology can modify or change the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or changes completed by those with ordinary knowledge in the technical field without departing from the spirit and technical idea disclosed by the present invention should still be covered by the claims of the present invention.

Claims

1. A method for determining the absolute structure of chiral organic crystals using electron diffraction, characterized in that, It includes the following steps: (1) Obtain the positive zone axis selected area electron diffraction pattern A of the crystal to be measured, the off-positive zone axis selected area electron diffraction pattern B, the software simulated electron diffraction pattern C, and the dynamical simulated electron diffraction pattern intensity diagrams D1 and D2. The positive zone axis selected area electron diffraction pattern A includes zero-order diffraction spots, and the off-positive zone axis selected area electron diffraction pattern B includes zero-order diffraction spots and first-order diffraction spots. When obtaining the off-positive zone axis selected area electron diffraction pattern B, the angle by which the crystal to be measured rotates off the positive zone axis is 0 - 5°; (2) Superimpose the positive zone axis selected area electron diffraction pattern A and the off-positive zone axis selected area electron diffraction pattern B in step (1) to obtain the experimental reconstructed electron diffraction pattern E; (3) Compare the software simulated electron diffraction pattern C obtained in step (1) with the experimental reconstructed electron diffraction pattern E obtained in step (2), and rotate the direction of the experimental reconstructed electron diffraction pattern E so that the direction of the experimental reconstructed electron diffraction pattern E is consistent with the direction of the software simulated electron diffraction pattern C, thereby determining the absolute direction of the experimental reconstructed electron diffraction pattern E of the crystal to be measured; (4) Extract the integrated intensity of the electron diffraction spots in the positive zone axis selected area electron diffraction pattern A described in step (1), and input this integrated intensity into the experimental reconstructed electron diffraction pattern E obtained in step (2) to obtain the experimental electron diffraction pattern intensity diagram F; (5) Compare the matching degrees of the dynamical simulated electron diffraction pattern intensity diagrams D1 and D2 described in step (1) and the experimental electron diffraction pattern intensity diagram F described in step (4) respectively, thereby determining the absolute configuration of the crystal to be measured.

2. The method for determining the absolute structure of a chiral organic crystal by electron diffraction according to claim 1, characterized in that In step (1), the method for obtaining the dynamical simulated electron diffraction pattern intensity diagram D is: the Bloch-wave method in the crystallographic software JEMS.

3. The method for determining the absolute structure of a chiral organic crystal by electron diffraction according to claim 1, characterized in that, In step (1), the dynamical simulated electron diffraction pattern intensity diagrams D1 and D2 are the dynamical simulated electron diffraction pattern intensity diagrams of two enantiomers.

4. The method for determining the absolute structure of a chiral organic crystal using electron diffraction according to claim 1, wherein In step (1), the tool for the software simulated electron diffraction pattern C is: the crystallographic software JEMS.

5. The method for determining the absolute structure of a chiral organic crystal by electron diffraction according to claim 1, characterized in that, In step (4), the tool for extracting the integrated intensity is: the electron diffraction pattern processing software ED process.

6. The method for determining the absolute structure of a chiral organic crystal by electron diffraction according to claim 1, characterized in that, In step (5), the method for judging the matching degree is: compare the diffraction pairs with central symmetry in the experimental electron diffraction pattern intensity diagram F with the corresponding diffraction pairs with central symmetry in the two dynamical simulated electron diffraction pattern intensity diagrams D1 and D2 respectively, If the identical rate of the intensity relationship of the diffraction pairs between the dynamical simulated electron diffraction pattern intensity diagram D1 and the experimental electron diffraction pattern intensity diagram F > 50%, then the structure of the crystal to be measured is consistent with the absolute structure of the dynamical simulated electron diffraction pattern intensity diagram D1; If the identical rate of the intensity relationship of the diffraction pairs between the dynamical simulated electron diffraction pattern intensity diagram D2 and the experimental electron diffraction pattern intensity diagram F > 50%, then the structure of the crystal to be measured is consistent with the absolute structure of the dynamical simulated electron diffraction pattern intensity diagram D2.

7. The application of the method for determining the absolute structure of chiral organic crystals using electron diffraction according to any one of claims 1 - 6 in judging the absolute structure of nanocrystals.

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