Method for encoding atomic chemical environment and fast prediction of nuclear magnetic resonance chemical shifts

Abstract

The application discloses a method for atomic chemical environment coding and fast prediction of nuclear magnetic resonance chemical shift, and relates to the technical field of atomic coding and chemical shift prediction. The method comprises the following steps: defining the mapping relationship between atoms and symbols, and the mapping relationship between chemical bonds and symbols; defining a priority parameter; specifying any atom in a compound as a central atom, and coding all atoms in the compound with the central atom as the coding center. The mapping relationship between the atomic chemical environment coding and the chemical shift value of a standard organic compound and the test condition of the chemical shift are stored in a database; the structural formula of a compound to be predicted is input; after coding all atoms, the atomic coding data is matched with the atomic coding data in the database, so that the chemical shift of the unknown chemical shift compound is predicted. The application can accurately and uniquely describe the atomic chemical environment coding, and realizes simple, fast and accurate prediction of the nuclear magnetic resonance chemical shift based on the atomic chemical environment coding.

Description

Technical Field

[0001] This invention relates to the field of atomic coding and chemical shift prediction technology, and in particular to atomic chemical environment coding and a method for rapid prediction of nuclear magnetic resonance chemical shift. Background Technology

[0002] Precise descriptions of the chemical environment surrounding atoms have important applications in predicting compound properties and searching for substructures. Currently, compound coding primarily focuses on molecular-level structure coding, with one code per molecule, such as mol, smiles, inchi, and inchikey codes. However, these codes cannot describe the chemical environment of a single atom.

[0003] Nuclear magnetic resonance (NMR) is a unique characterization technique that is sensitive to the local chemical environment of atoms and has wide applications in physical, chemical, and biological systems. Due to the varying degrees of shielding effect of external magnetic fields within their chemical environments, atomic nuclei exhibit different chemical shifts in NMR spectra.

[0004] Calculating the electronic structure of a system using quantum mechanics-based ab initio computation or density functional theory (DFT) methods can directly yield chemical shifts, enabling precise identification of signal peaks. However, accurate calculation of electronic structure requires significant computational resources and is time-consuming, hindering practical applications. Machine learning methods can also be used to predict NMR chemical shifts, but these methods do not consider the mechanistic characteristics of NMR chemical shifts, require large datasets to achieve high accuracy, and place relatively high demands on computer configuration. Therefore, developing a simple, accurate, fast, and easily scalable method for calculating chemical shifts is crucial. Summary of the Invention

[0005] The purpose of this invention is to develop a coding system that can accurately and uniquely describe the atomic chemical environment, and based on the logic that similar chemical environments have similar chemical shifts, to achieve simple, accurate, and rapid prediction of nuclear magnetic resonance chemical shifts.

[0006] This invention provides atomic chemical environment coding, including the following steps:

[0007] The mapping relationships between atoms and symbols, and between chemical bonds and symbols are defined respectively, resulting in the following mapping table 1 and mapping table 2;

[0008] The mapping relationship between atoms and symbols is shown in Table 1:

[0009] Table 1. Correspondence between atoms and symbols

[0010]

[0011] The mapping relationship between chemical bonds and symbols is shown in Table 2:

[0012] Table 2 Correspondence between chemical bonds and symbols

[0013]

[0014] The priority parameters of atoms and chemical bonds are defined respectively, resulting in Tables 3 and 4;

[0015] The priority parameters of atoms are shown in Table 3:

[0016] Table 3 Priority parameters of atoms

[0017]

[0018] The chemical bond priority parameters are shown in Table 4:

[0019] Table 4. Priority parameters of chemical bonds

[0020]

[0021] Select any atom in a specified compound as the central atom, and encode using the central atom as the encoding center, including:

[0022] The chemical environment encoding of the central atom is: central atom symbol - number of atoms connected to the central atom with a bond number of 1 - size of the ring containing the central atom; if the central atom is not on a ring, the size of the ring containing the central atom is 0.

[0023] The chemical environment encoding of other atoms in the compound:

[0024] Identify all atoms with a bond number of 1 connected to the central atom, and determine the characteristic parameters of all atoms with a bond number of 1. The characteristic parameters include the atom symbol, the type of chemical bond with the central atom, the total number of adjacent atoms, and the number of adjacent non-hydrogen atoms. Convert the characteristic parameters into priority parameters. Sort the atoms according to their priority parameters.

[0025] The sorted atoms are converted into codes according to the mapping relationship. The coding rule is: chemical bond symbol + atom symbol.

[0026] Encode all atoms connected to the central atom in sequence, with numbers of 2, 3, 4...N, until all atoms in the compound have been traversed, where N is an integer greater than 1;

[0027] Repeat the above steps to complete the chemical environment coding of all atoms in the compound when any one atom in the compound is taken as the central atom.

[0028] Furthermore, the conversion method between the feature parameters and the priority parameters is as follows:

[0029] The priority parameters include priority parameters for atomic symbols, priority parameters for the type of chemical bond between the atom and the central atom, priority parameters for the total number of adjacent atoms, and priority parameters for the number of adjacent non-hydrogen atoms.

[0030] The priority parameter for the total number of adjacent atoms is the reciprocal of the sum of the total number of adjacent atoms and 1, and the priority parameter for the number of adjacent non-hydrogen atoms is the reciprocal of the sum of the number of adjacent non-hydrogen atoms and 1.

[0031] Furthermore, the sorting rules for atoms in the encoding are as follows: the priority parameters of the connecting atoms are compared in order of priority, bond priority, number of adjacent atoms, and number of adjacent non-hydrogen atoms. The smaller priority parameter value is placed first. If the values ​​are the same, the next priority parameter value is compared until all atoms are sorted.

[0032] Furthermore, if the type of connecting bond is a double bond, and the atoms connected by the double bond are all C atoms, the encoding rule is: cis-trans isomer symbol + chemical bond symbol + atom symbol;

[0033] Furthermore, the C atom located on the same side of the double bond as the central atom is designated as a cis isomer; the C atom located on a different side of the double bond than the central atom is designated as a trans isomer.

[0034] Furthermore, if the connecting atom is a chiral center, the atoms connected to the chiral center must first be sorted according to the sorting rules to determine the first atom. Then, the remaining atoms are sorted in a clockwise direction, and a first custom symbol is added before the code produced by these atoms to distinguish chiral isomers.

[0035] Furthermore, if the atom is on a ring, the encoding rule for repeating atoms is: chemical bond symbol + second custom symbol + atom symbol, and atoms with higher connection numbers connected to it are no longer recorded.

[0036] A method for rapidly predicting nuclear magnetic resonance chemical shifts includes the following steps:

[0037] A nuclear magnetic resonance chemical shift database was constructed, which stores the mapping relationship between the atomic chemical environment codes of standard organic compounds and their chemical shift values, as well as the test conditions for the chemical shift.

[0038] Input the chemical structure data of the organic compound to be tested, and convert the chemical structure information into atomic chemical environment codes;

[0039] The obtained atomic chemical environment code is matched with the atomic chemical environment codes of standard organic compounds stored in the database, and a standard atomic code or a similar standard atomic chemical environment code fragment that is the same as the atomic chemical environment code to be tested is found.

[0040] The matched atomic chemical environment codes are mapped to the corresponding chemical shift values ​​in the database. The average and standard deviation of all matched chemical shift values ​​are calculated to obtain the predicted nuclear magnetic resonance chemical shift of the organic compound to be tested and its accuracy.

[0041] Furthermore, the input type of the chemical structure data of the organic compound to be tested includes any one of mol encoding, smiles encoding, or inchi encoding.

[0042] Furthermore, before matching the atomic chemical environment encoding of standard organic compounds in the database, the process also includes: splitting the atomic encoding according to the connection symbols to obtain multiple substructures to be predicted;

[0043] Traverse the database for standard atomic chemical structure codes that are the same as or similar to multiple test substructures;

[0044] The method of splitting atomic codes involves breaking down the structure of the organic compound to be tested into multiple predicted substructures with gradually decreasing lengths.

[0045] "Ring size" refers to the number of atoms in the ring that makes up the atom;

[0046] "Number of connections with the central atom" refers to the number of chemical bonds that connect other atoms in a compound to the central atom in a straight chain. If other atoms are directly connected to the central atom by chemical bonds, the number of connections between that atom and the central atom is 1. If there are n other atoms in the straight chain connecting other atoms to the central atom, and each additional atom adds one more chemical bond to the straight chain, then the number of chemical bonds in the straight chain connecting that atom to the central atom is n+1, that is, the number of connections between that atom and the central atom is n+1, where n is an integer greater than 0.

[0047] The beneficial effects of this invention are:

[0048] This invention provides a coding system that can accurately and uniquely describe the atomic chemical environment, and based on this atomic chemical environment coding, enables simple, fast, and accurate prediction of nuclear magnetic resonance chemical shifts. Attached Figure Description

[0049] Figure 1 Methods for predicting nuclear magnetic resonance chemical shift. Implementation

[0050] The technical solution of the present invention is described clearly and completely below. Obviously, the embodiments described herein are only a part of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the protection scope of the present invention.

[0051] The numbers marked in the compound structural formulas of this invention represent only the serial numbers of the atoms in the compound structure. Example 1

[0052] Based on compound A, if atom 1 in compound A is selected as the central atom, then the chemical environment code of the central atom is: central atom symbol - number of atoms connected to the central atom with a number of 1 - size of the ring in which the central atom is located. When atom 1 is the central atom, the atom symbol is C, the number of atoms connected to the central atom with a number of 1 is 3, atom 1 is not on the ring, and the size of the ring in which the central atom is located is 0. Therefore, the chemical environment code of the central atom is 'C-3-0'.

[0053] The structural formula of compound A is as follows:

[0054]

[0055] All atoms connected to the central atom with a bond number of 1 were identified as atoms 2, 3, and 4. The information of the atoms and chemical bonds connected to them was recorded, as shown in Table 5.

[0056] Table 5 shows the characteristic parameters of all atoms connected to the central atom with a bond number of 1 and their chemical bonds:

[0057] Table 5. Characteristic parameters of all atoms connected to the central atom with a bond number of 1 and their chemical bonds.

[0058]

[0059] Based on the priority rules defined in Tables 3 and 4, the characteristic parameters in Table 5 are converted into priority parameters. The priority parameters for the total number of adjacent atoms and the number of adjacent non-hydrogen atoms are the reciprocal of the sum of their quantities and 1. The connecting atoms are then sorted according to their priority, bond priority, number of adjacent atoms, and number of adjacent non-hydrogen atoms, in that order. The priority order of each atom after sorting is recorded, as shown in Table 6.

[0060] Table 6. Priority parameters and sorting results for all atoms connected to the central atom with a connection number of 1.

[0061]

[0062] Comparing the priority parameters in Table 6, the priority parameters of the atomic symbols of atoms 3 and 4 are smaller than that of atom 2, so atoms 3 and 4 are ranked before atom 2. Since the priority parameters of the atomic symbols of atoms 3 and 4 are both 2, we continue to compare the bond types of atoms 3 and 4. The priority parameters of the bond types of atoms 3 and 4 are equal, both being 4. Therefore, we need to continue to compare the priority parameters of the total number of adjacent atoms. The priority parameter of the total number of adjacent atoms of atom 3 is 0.2, which is less than the priority parameter of the total number of adjacent atoms of atom 4 is 0.25. Therefore, atom 3 is ranked before atom 4. Thus, the atomic order after sorting the atoms connected to the central atom with a number of 1 is 3, 4, 2.

[0063] Based on the correspondence defined in Tables 1 and 2, the sorted atoms are converted into codes in sequence, with the coding rule being: chemical bond symbol + atom symbol.

[0064] For atoms 3, 4, and 2, their connecting bond symbols plus atom symbols are 'C', 'C', and '=O', respectively. Then, they are concatenated in order to form 'CC=O'.

[0065] Then connect this code with the chemical environment code 'C-3-0' of the central atom using the '|' symbol, which is 'C-3-0|CC=O|'.

[0066] Identify all atoms in compound A that have a bond number of 2 connected to the central atom, namely atoms connected to atoms 3, 4, and 2 respectively. Atoms connected to atom 3 are 7, 8, and 9 respectively, and atoms connected to atom 4 are 5 and 6 respectively. Atom 2 has no bonded atoms. Record the information of all atoms with a bond number of 2 and their chemical bonds, as shown in Table 7.

[0067] Table 7. Characteristic parameters of all atoms connected to the central atom with a bond number of 1 and their chemical bonds.

[0068]

[0069] Based on the priority rules defined in Tables 3 and 4, the feature parameters in Table 7 are converted into priority parameters (where the priority parameters for the total number of adjacent atoms and the number of adjacent non-hydrogen atoms are the reciprocal of the sum of their quantities and 1). Furthermore, the sorted atomic priority order obtained in step 4 needs to be added to the parameters for this sorting. The connecting atoms are then sorted according to the primary and secondary order of atomic priority, atomic priority, bond priority, number of adjacent atoms, and number of adjacent non-hydrogen atoms after the previous sorting, resulting in the atomic arrangement order shown in Table 8.

[0070] Table 8. Priority parameters and sorting results for all atoms connected to the central atom with a connection number of 2.

[0071]

[0072] According to the above sorting rules, based on the atomic sorting with a connection number of 1 to the central atom, the sorted atomic order is 7, 9, 8, 6, 5.

[0073] Based on the correspondence defined in Tables 1 and 2, the sorted atoms are converted into codes, with the coding rule being: chemical bond symbol + atom symbol.

[0074] For atoms 7, 9, and 8, the connecting bond symbol + atom symbol are 'H', 'C', and 'C' respectively. Then, they are concatenated in order to form 'HCC'.

[0075] For atoms 6 and 5, the connecting bond symbol + atom symbol are '=C' and 'O' respectively, and then they are concatenated in order to form '=CO'.

[0076] For atoms with a connection number of 1, the atoms that generate atoms with a connection number of 2 are separated by ','. For example, atoms 7, 9, and 8 are connected to atom 3, and atoms 6 and 5 are connected to atom 4. Therefore, the codes generated by these two types of atoms need to be separated by ',', which is: 'HCC,=CO'.

[0077] Then, connect this code with the codes generated by other atoms whose connection number to the central atom is 1, according to priority order, using the '|' symbol, which is 'C-3-0|CC=O|HCC,=CO|'.

[0078] Repeat the above steps to obtain the connecting atoms with connection numbers of 3, 4, 5, 6... until all atoms in the compound have been traversed.

[0079] Taking atom 1 in compound A as the central atom as an example, the final code obtained is:

[0080] 'C-3-0|CC=O|HCC,=CO|=CC,HHH, / C\C,H|\H / H,HHH,HHH,HHH|'. Example 2

[0081] Based on Example 1 and Compound A, according to the coding rules described in Example 1, if the type of connecting bond is a double bond and the atoms connected by the double bond are all C atoms, the coding rule is: cis-trans isomer symbol (cis: '\', trans: ' / ') + chemical bond symbol + atom symbol.

[0082] Compound A selects atom number 18 as the central atom:

[0083] When the number of connections is 3, atoms 1 and 18 are on the same side, forming a cis configuration, and their cis-trans isomer symbol is '\'. Therefore, the code for atom 1 is '\C'. Atom 5 and 18 are not on the same side, forming a trans configuration, and their cis-trans isomer symbol is ' / '. Therefore, the code for atom 5 is ' / O'.

[0084] With atom 18 as the central atom, the encoding when the number of connections is 3 is: 'C-4-0|HHHC|=CC|\C / O,HHH|'.

[0085] Similarly, when atom 17 is chosen as the central atom, atom 1 and atom 17 are not on the same side, and have a trans structure. The symbol for its cis-trans isomerism is ' / ', so the code for atom 1 is ' / C'; atom 5 and atom 17 are on the same side, and have a cis structure. The symbol for its cis-trans isomerism is '\', so the code for atom 5 is '\O'.

[0086] With atom 17 as the central atom, the encoding when the number of connections is 3 is: 'C-4-0|HHHC|=CC| / C\O,HHH|'.

[0087] By comparing the central atoms 18 and 17, we can find that their codes are different, thus distinguishing cis-trans isomers, which represent the different chemical environments of atoms 18 and 17.

[0088] By repeating the above steps, the atomic chemical environment codes of all atoms can be obtained sequentially when any atom in compound A is used as the central atom, as follows:

[0089] 1: C-3-0|CC=O|HCC,=CO|=CC,HHH, / C\C,H|\H / H,HHH,HHH,HHH|;

[0090] 2: O-1-0|=C|CC|HCC,=CO|=CC,HHH, / C\C,H|\H / H,HHH,HHH,HHH|;

[0091] 3: C-4-0|HCCC|C=O,=CC,HHH|=CO,\H / H,HHH| / C\C,H|HHH,HHH|;

[0092] 4: C-3-0|=CCO|CC,C=O,H|HHH,HHH,HCC|=CC,HHH|\H / H,HHH|;

[0093] 5: O-2-0|HC|=CC|\C / C,C=O|HHH,HHH,HCC|=CC,HHH|\H / H,HHH|;

[0094] 6: C-3-0|=CCC|CO,HHH,HHH|C=O,H|HCC|=CC,HHH|\H / H,HHH|;

[0095] 7: H-1-0|C|CCC|C=O,=CC,HHH|=CO,\H / H,HHH| / C\C,H|HHH,HHH|;

[0096] 8: C-3-0|=CCC|HH,HCC,HHH|C=O,HHH|=CO| / C\C,H|HHH,HHH|;

[0097] 9: C-4-0|HHHC|HCC|C=O,=CC|=CO,\H / H,HHH| / C\C,H|HHH,HHH|;

[0098] 10: H-1-0|C|HHC|HCC|C=O,=CC|=CO,\H / H,HHH| / C\C,H|HHH,HHH|;

[0099] 11: H-1-0|C|HHC|HCC|C=O,=CC|=CO,\H / H,HHH| / C\C,H|HHH,HHH|;

[0100] 12: H-1-0|C|HHC|HCC|C=O,=CC|=CO,\H / H,HHH| / C\C,H|HHH,HHH|;

[0101] 13: H-1-0|O|C|=CC|\C / C,C=O|HHH,HHH,HCC|=CC,HHH|\H / H,HHH|;

[0102] 14: H-1-0|C|HHC|=CC| / C\O,HHH|C=O,H|HCC|=CC,HHH|\H / H,HHH|;

[0103] 15: H-1-0|C|HHC|=CC| / C\O,HHH|C=O,H|HCC|=CC,HHH|\H / H,HHH|;

[0104] 16: H-1-0|C|HHC|=CC| / C\O,HHH|C=O,H|HCC|=CC,HHH|\H / H,HHH|;

[0105] 17: C-4-0|HHHC|=CC| / C\O,HHH|C=O,H|HCC|=CC,HHH|\H / H,HHH|;

[0106] 18: C-4-0|HHHC|=CC|\C / O,HHH|C=O,H|HCC|=CC,HHH|\H / H,HHH|;

[0107] 19: H-1-0|C|HHC|=CC|\C / O,HHH|C=O,H|HCC|=CC,HHH|\H / H,HHH|;

[0108] 20: H-1-0|C|HHC|=CC|\C / O,HHH|C=O,H|HCC|=CC,HHH|\H / H,HHH|;

[0109] 21: H-1-0|C|HHC|=CC|\C / O,HHH|C=O,H|HCC|=CC,HHH|\H / H,HHH|;

[0110] 22: H-1-0|C|HHC|=CC| / H\H,HCC|C=O,HHH|=CO| / C\C,H|HHH,HHH|;

[0111] 23: H-1-0|C|HHC|=CC| / H\H,HCC|C=O,HHH|=CO| / C\C,H|HHH,HHH|;

[0112] 24: H-1-0|C|HHC|=CC| / H\H,HCC|C=O,HHH|=CO| / C\C,H|HHH,HHH|

[0113] 25: H-1-0|C|H=C| / C\C|HCC,HHH|C=O,HHH|=CO| / C\C,H|HHH,HHH|;

[0114] 26: C-4-0|HHHC|=CC| / H\H,HCC|C=O,HHH|=CO| / C\C,H|HHH,HHH|;

[0115] 27: C-3-0|HH=C|CC|HCC,HHH|C=O,HHH|=CO| / C\C,H|HHH,HHH|;

[0116] 28: H-1-0|C|H=C|\C / C|HCC,HHH|C=O,HHH|=CO| / C\C,H|HHH,HHH|. Example 3

[0117] Based on Example 1 and Compound B and Compound C.

[0118] The structural formula of compound B is as follows:

[0119]

[0120] The structural formula of compound C is as follows:

[0121]

[0122] Compound B and compound C are chiral isomers of each other.

[0123] Using atom 5 in compound B as the central atom, when the connection number is 2, atoms 11, 12, and 13 are connected to atom 6, and atom 6 is the chiral center;

[0124] Therefore, atoms 11, 12, and 13 need to be sorted according to the sorting rules in Example 1, resulting in 13, 12, and 11; then, starting with atom 13, they are arranged clockwise, resulting in 13, 11, and 12; then, they are converted into atomic chemical environment codes according to the coding rules, and the '@' symbol is added before them, resulting in '@HFC'; according to this rule, when atom 5 is the central atom, the atomic chemical environment code when the number of connections is 2 is: 'C-3-0|=CCC|CC,@HFC,HHH|'.

[0125] Similarly, in compound C, atom number 5 is the central atom. According to this rule, the code for central atom number 5 when the connection number is 2 is: 'C-3-0|=CCC|CC,@HCF,HHH|'.

[0126] When atom 5 in compound B and compound C is the central atom, its coding is different, thus chiral isomers can be distinguished. Example 4

[0127] Based on Example 1 and Compound D.

[0128] The structural formula of compound D is as follows:

[0129]

[0130] If an atom is on a ring, the coding rule for repeating atoms is: chemical bond symbol + '$' + atom symbol, and atoms with higher connection numbers connected to it are no longer recorded.

[0131] Atom 5 of compound D is selected as the central atom: when the number of connections is 3, atom 2 comes from both atom 1 and atom 3, that is, atom 2 is a repeating atom.

[0132] When the atom connected to atom 1 is recorded first, atoms 2 and 7 are converted into codes according to the encoding rules in Example 1, and the result is 'C=O'.

[0133] When recording the atoms connected to atom 3, we have 2, 15, and 16. Atom 2 has already been recorded. Atom 2 connected to atom 3 is a repeating atom. Therefore, the coding rule for atom 2 connected to atom 3 is: chemical bond symbol + '$' + atom symbol, which is converted to the code 'HH$C'.

[0134] Therefore, the encoding when the number of connections is 3 is: 'C-4-6|HHCC|HHC,HHC|C=O,HH$C|'.

[0135] Since atom 2, which is connected to atom 3, is a repeating atom, atoms with higher connection numbers connected to this repeating atom 2 are no longer recorded. Only atoms with higher connection numbers connected to atom 2, which is connected to atom 1, are recorded. Therefore, when the connection number is 4, atoms 3 and 8 connected to atom 2 need to be recorded. Since atom 3, which is connected to atom 2, is also a repeating atom, atom 3 is coded as '$C' and atom 8 is coded as 'C'. The combined code is '$CC'.

[0136] Therefore, the encoding when the number of connections is 4 is: C-4-6|HHCC|HHC,HHC|C=O,HH$C|$CC|'. Example 5

[0137] This embodiment takes the data collection and storage of benzoic acid as an example, collecting the atomic chemical environment codes of benzoic acid and storing them in a database:

[0138] The structural formula of benzoic acid is as follows:

[0139]

[0140] Generate atomic codes

[0141] 10: H-1-0|C|:C:C|:CC,H:C|H:C,=OO,H:$C|H:$C,H|;

[0142] 11: H-1-0|C|:C:C|:CC,H:C|H:C,=OO,H:$C|H:$C,H|;

[0143] 12: H-1-0|O|C|C=O|:C:C|H:C,H:C|H:C,H:$C|H:$C|;

[0144] 13: H-1-0|C|:C:C|H:C,H:C|:CC,H:$C|H:$C,=OO|H|;

[0145] 14: H-1-0|C|:C:C|H:C,H:C|:CC,H:$C|H:$C,=OO|H|;

[0146] 15: H-1-0|C|:C:C|H:C,H:C|H:C,H:$C|:$CC|=OO|H|.

[0147] 2. Based on the collected NMR data, specify the chemical shift for each hydrogen atom and the test conditions for that chemical shift.

[0148] Atom number: chemical shift, solvent, temperature

[0149] 10: 8.12, CDCl3, 298K

[0150] 11: 8.12, CDCl3, 298K

[0151] 12: 12.09, CDCl3, 298K

[0152] 13: 7.45, CDCl3, 298K

[0153] 14: 7.45, CDCl3, 298K

[0154] 15: 7.62, CDCl3, 298K

[0155] 3. Establish the relationship between coding and chemical shift to form data.

[0156] Taking atoms 10 and 12 as examples:

[0157] Input the chemical structural formula data of atom number 10 into the database, including:

[0158] The inchikey of the compound to which atom 10 belongs: WPYMKLBDIGXBTP-UHFFFAOYSA-N;

[0159] Chemical environment code: H-1-0|C|:C:C|:CC,H:C|H:C,=OO,H:$C|H:$C,H|;

[0160] Chemical shift: 8.12;

[0161] The test solvent for the chemical shift is CDCl3;

[0162] Test temperature: 298.0K;

[0163] Input the chemical structural formula data of atom number 12 into the database, including:

[0164] The inchikey of the compound to which atom 12 belongs: WPYMKLBDIGXBTP-UHFFFAOYSA-N;

[0165] Chemical environment code: H-1-0|O|C|C=O|:C:C|H:C,H:C|H:C,H:$C|H:$C|;

[0166] Chemical shift: 12.09;

[0167] The test solvent for the chemical shift is CDCl3;

[0168] Test temperature: 298.0K;

[0169] 4. After collecting data on all atoms of benzoic acid, store the data in the database. Example 6

[0170] Predict the H nuclear magnetic resonance chemical shift of the following compound M as an example:

[0171] The structural formula of compound M is as follows:

[0172]

[0173] 1. Generate atomic codes

[0174] 10: H-1-0|C|@HCC|@HHC,:C:N|@HH$C,:C$C,:C|H:C,H:$C|H:$C|;

[0175] 11: H-1-0|C|@HCC|:C:N,@HHC|:C$C,:C,@HH$C|H:C,H:$C|H:$C|;

[0176] 12: H-1-0|C|@HCC|:C:C,@HHC|$C:N,H:C,@HH$C|:C,H:$C|H:$C|;

[0177] 13: H-1-0|C|@HCC|@HHC,:C:C|@HH$C,$C:N,H:C|:C,H:$C|H:$C|;

[0178] 14: H-1-0|C|:C:C|:CC,H:C|C:N,@HHC,H:$N|@HH$C,:$C,@HH$C|;

[0179] 15: H-1-0|C|@HCC|@HHC,@HHC|:$C:C,:$C:N|H:C,:C|H:$C,H:$C|;

[0180] 16: H-1-0|C|@HCC|@HHC,@HHC|:$C:N,:$C:C|:C,H:C|H:$C,H:$C|;

[0181] 17: H-1-0|C|:C:N|H:C,:C|H:C,:$CC|:$CC,@HHC|@HH$C,@HH$C|;

[0182] 18: H-1-0|C|:C:C|H:C,H:N|:CC,:$C|C:$N,@HHC|@HH$C,@HH$C|.

[0183] 2. Generate a prediction model

[0184] Using atom 17 as an example, a prediction model is generated: [

[0186] H-1-0|C|:C:N|H:C,:C|H:C,:$CC|:$CC,@HHC|@HH$C,@HH$C|;

[0187] H-1-0|C|:C:N|H:C,:C|H:C,:$CC|:$CC,@HHC|;

[0188] H-1-0|C|:C:N|H:C,:C|H:C,:$CC|;

[0189] H-1-0|C|:C:N|H:C,:C|;

[0190] H-1-0|C|:C:N|. ]

[0192] 3. Prediction Module

[0193] Taking atom number 17 as an example:

[0194] Based on the generated prediction model, it is matched sequentially with the codes in the database until a match is successful. When the prediction structure is H-1-0|C|:C:N|H:C,:C|H:C,:$CC|:$CC,@HHC|, the following data is matched:

[0195] Inchikey of compound E: NAMUJTUXPIHBEJ-UHFFFAOYSA-N;

[0196] Chemical environment code: H-1-0|C|:C:N|H:C,:C|H:C,:$CC|:$CC,@HHC|:C:N,@HH$C|

[0197] :C$C,H:C|:C=N,:$C:C|:$C:C,H,H:C|H:C,:$CO|:$CO,C|;

[0198] Chemical shift: 8.62;

[0199] The test solvent for the chemical shift is CDCl3;

[0200] Test temperature: 298.0K;

[0201] Inchikey of compound F: ZGFYOFQNJQLZAX-RVVQFRNZSA-N;

[0202] Chemical environment code: H-1-0|C|:C:N|H:C,:C|H:C,:$CC|:$CC,@HHC|=CC,:$C:C|

[0203] / H\N,:$C:C,H:C|=C,H:C,H:$C|HC,H:$C|:C:C|H:C,H:C|;

[0204] Chemical shift: 8.56;

[0205] The test solvent for the chemical shift is CDCl3;

[0206] Test temperature: 298.0K;

[0207] Based on the chemical shift values ​​(8.62, 8.56) in the matching results, the average value was calculated to be 8.59, and the standard deviation was 0.042.

[0208] Repeat the above steps to complete the NMR prediction process for all hydrogen atoms and return the NMR prediction results.

[0209] The structural formula of compound E is as follows:

[0210]

[0211] The structural formula of compound F is as follows:

[0212]

[0213] The two data points above correspond to atoms 34 and 26 in compounds E and F, respectively, as shown in the figure. By comparing atom 17 of the predicted compound with atoms 34 and 26 of the matched compound, it can be seen that they have similar chemical environments and therefore similar chemical shifts. Thus, this technique can be used to predict the chemical shifts of compounds using nuclear magnetic resonance.

Claims

1. A method for rapidly predicting nuclear magnetic resonance chemical shifts, implemented based on atomic chemical environment coding, characterized in that... Includes the following steps: A nuclear magnetic resonance chemical shift database was constructed, which stores the mapping relationship between the atomic chemical environment codes of standard organic compounds and their chemical shift values, as well as the test conditions for the chemical shift. Input the chemical structure data of the organic compound to be tested, and convert the chemical structure data into atomic chemical environment codes; The obtained atomic chemical environment code is matched with the atomic chemical environment codes of standard organic compounds stored in the database, and a standard atomic code or a similar standard atomic chemical environment code fragment that is the same as the atomic chemical environment code to be tested is found. The matched atomic chemical environment codes are mapped to the corresponding chemical shift values ​​in the database. The average and standard deviation of all matched chemical shift values ​​are calculated to obtain the predicted nuclear magnetic resonance chemical shift of the organic compound to be tested and its accuracy. The atomic chemical environment coding includes the following steps: Define the mapping relationships between atoms and symbols, and between chemical bonds and symbols, respectively; Define the priority parameters for chemical bonds and the priority parameters for atoms respectively; Select any atom in a specified compound as the central atom, and encode using the central atom as the encoding center, including: The chemical environment encoding of the central atom is: central atom symbol - number of atoms connected to the central atom with a bond number of 1 - size of the ring containing the central atom; if the central atom is not on a ring, the size of the ring containing the central atom is 0. The chemical environment encoding of other atoms in the compound: Identify all atoms with a bond number of 1 connected to the central atom, and determine the characteristic parameters of all atoms with a bond number of 1. The characteristic parameters include the atom symbol, the type of chemical bond with the central atom, the total number of adjacent atoms, and the number of adjacent non-hydrogen atoms. Convert the characteristic parameters into priority parameters. Sort the atoms according to the size of the priority parameters. The sorted atoms are converted into codes according to the mapping relationship. The coding rule is: chemical bond symbol + atom symbol. Encode all atoms connected to the central atom in sequence, with numbers of 2, 3, 4...N, until all atoms in the compound have been traversed, where N is an integer greater than 1; Repeat the above steps to complete the chemical environment coding of all atoms in the compound when any one atom in the compound is taken as the central atom.

2. The method for rapidly predicting nuclear magnetic resonance chemical shift according to claim 1, characterized in that, The input type for the chemical structure data of the organic compound to be tested includes any one of mol encoding, smiles encoding, or inchi encoding.

3. The method for rapidly predicting nuclear magnetic resonance chemical shift according to claim 1, characterized in that, Before matching the atomic chemical environment encoding of standard organic compounds in the database, the process also includes: splitting the atomic encoding according to the connection symbols to obtain multiple predicted substructures; Traverse the database for standard atomic chemical structure codes that are the same as or similar to multiple test substructures; The method of splitting atomic codes involves breaking down the structure of the organic compound to be tested into multiple predicted substructures with gradually decreasing lengths.

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