Method and system for identifying structure of compound

Patent metadata

Field	Value
Publication number	US-11573201-B2
Application number	US-201917251523-A
Country	US
Kind code	B2
Filing date	Jun 14, 2019
Priority date	Jun 15, 2018
Publication date	Feb 7, 2023
Grant date	Feb 7, 2023

Abstract

The present invention relates to a method for identifying a chemical structure of a wide variety of low molecular weight compounds using mass-to-charge ratio and collision cross section of fragment ions of an analyte compound. The analyte compound is ionized and fragmented, and the fragment ions are measured by a mass spectrometer with an ion mobility spectrometry measurement device. According to the present method, it does not depend on any compound class-specific characteristics or structural features, therefore enabling determinations of any classes of low molecular weight compounds, which does not limit to a specific compound class. The present invention comprises three methods which share a common data structure and s data processing method.

First claim

The invention claimed is:

1. A method for identifying the structure of a compound, which comprises:
deducing a mass and/or elemental composition of an analyte compound from mass-to-charge ratios (m/z) of fragment ions and a precursor ion of the analyte compound,
acquiring a candidate structure by searching from chemical structures included in a chemical structure database based on the deduced mass and/or elemental composition of the analyte compound or generating a theoretically existing structure based on the elemental composition,
acquiring structures of estimated fragment ions of the candidate structure by systematic bond cleavage or a fragmentation prediction model,
acquiring collision cross sections (CCS) of the estimated fragment ions by searching from a reference spectral database in which structures, mass-to-charge ratios and collision cross sections of fragment ions of a standard compound are combined and a theoretical spectral database comprising structures of fragment ions and theoretically calculated CCSs, or by calculation and prediction based on the structures of the estimated fragment ions, and
matching the measured m/z ratios and CCSs of fragment ions of the analyte compound to the acquired m/z ratios and CCSs of the estimated fragment ions of the candidate structure.

2. The method according to claim 1 , wherein
in acquiring a candidate structure, instead of or in addition to acquiring a candidate structure from chemical structures included in a chemical structure database, a candidate structure is acquired from chemical structures generated with an algorithm of molecular structure generation for generating a theoretically possible structure based on the estimated elemental composition of the analyte compound.

3. A method for identifying the structure of a compound, which comprises:
matching measured mass-to-charge ratios (m/z) and collision cross sections (CCS) of fragment ions of an analyte compound to a reference spectral database in which structures, mass-to-charge ratios and collision cross sections of fragment ions of a standard compound are combined and a theoretical spectral database comprising structures of fragment ions and theoretically calculated CCSs thereof,
acquiring a registered structure of fragment ions matched with a predetermined tolerance as a potential substructure of the analyte compound,
acquiring a candidate structure of the analyte compound by searching a chemical structure having the substructure in a chemical structure database,
acquiring structures of estimated fragment ions of the candidate structure by systematic bond cleavage or a fragmentation prediction model,
acquiring CCSs of the estimated fragment ions by searching from a reference spectral database in which structures, mass-to-charge ratios and collision cross sections of fragment ions of a standard compound are combined and a theoretical spectral database comprising structures of fragment ions and theoretically calculated CCSs thereof, or by calculation and prediction based on the structures of the estimated fragment ions, and
matching the measured m/z ratios and CCSs of fragment ions of the analyte compound to the m/z ratios and the acquired CCSs of the estimated fragment ions of the candidate structure.

4. The method according to claim 3 , wherein
in acquiring a candidate structure, instead of acquiring a candidate structure by searching a chemical structure having the substructure in a chemical structure database, a candidate substructure is acquired by matching the observed mass-to-charge ratios and collision cross sections of the fragment ions to a reference spectral database in which structures, mass-to-charge ratios and collision cross sections of fragment ions of a standard compound are combined and a theoretical spectral database comprising structures of fragment ions and theoretically calculated CCSs thereof, and a candidate structure is acquired from chemical structures generated with an algorithm of molecular structure generation for generating a theoretically possible structure based on the substructure and the estimated elemental composition of the analyte compound.

5. A system for identifying the structure of a compound, which comprises:
a spectral data generation means for generating spectral data in which measured mass-to-charge ratios (m/z) and collision cross sections (CCS) of fragment ions of an analyte compound are combined, from a result of mass spectrometry of the analyte compound,
a reference spectral database comprising reference spectral data in which structures of fragment ions of a standard compound and mass-to-charge ratios and collision cross sections of fragment ions thereof are combined,
a theoretical spectral database comprising structures of fragment ions and theoretically calculated CCSs thereof,
a matching means for matching the spectral data to data in the reference spectral database and the theoretical spectral database,
a means for generating a candidate structure from structural information in the reference spectral database and the theoretical spectral database, and
an output means for outputting a result obtained by the matching means,
wherein the spectral data generation means and the output means are connected to the reference spectral database, the theoretical spectral database, the candidate information generation means and the matching means via a communication network outside the system.

6. A method for identifying the structure of a compound, which comprises:
deducing a mass and/or elemental composition of an analyte compound from mass-to-charge ratios (m/z) of fragment ions and a precursor ion of the analyte compound,
acquiring a candidate structure by searching from chemical structures included in a chemical structure database based on the deduced mass and/or elemental composition of the analyte compound or generating a theoretically existing structure based on the elemental composition,
acquiring structures of estimated fragment ions of the candidate structure by systematic bond cleavage or a fragmentation prediction model,
acquiring collision cross sections (CCS) of the estimated fragment ions by searching from a reference spectral database in which structures, mass-to-charge ratios and collision cross sections of fragment ions of a standard compound are combined, or by calculation and prediction based on the structures of the estimated fragment ions, and
matching the measured m/z ratios and CCSs of fragment ions of the analyte compound to the acquired m/z ratios and CCSs of the estimated fragment ions of the candidate structure.

7. A method for identifying the structure of a compound, which comprises:
deducing a mass and/or elemental composition of an analyte compound from mass-to-charge ratios (m/z) of fragment ions and a precursor ion of the analyte compound,
acquiring a candidate structure by searching from chemical structures included in a chemical structure database based on the deduced mass and/or elemental composition of the analyte compound or generating a theoretically existing structure based on the elemental composition,
acquiring structures of estimated fragment ions of the candidate structure by systematic bond cleavage or a fragmentation prediction model,
acquiring collision cross sections (CCS) of the estimated fragment ions by searching from a theoretical spectral database comprising structures of fragment ions and theoretically calculated CCSs, or by calculation and prediction based on the structures of the estimated fragment ions, and
matching the measured m/z ratios and CCSs of fragment ions of the analyte compound to the acquired m/z ratios and CCSs of the estimated fragment ions of the candidate structure.

8. A method for identifying the structure of a

Assignees

• Okinawa Inst Science & Tech School Corp

Inventors

• Hayakawa Eisuke

Classifications

• G01N27/623 Primary

  combined with mass spectrometry · CPC title

• H01J49/0036

  Step by step routines describing the handling of the data generated during a measurement · CPC title

• H01J49/0045

  characterised by the fragmentation or other specific reaction · CPC title