2021 Fiscal Year Research-status Report
Collision-induced isomerization in tandem mass spectrometry
| Project/Area Number |
21K05138
|
|---|
| Research Institution | Institute of Physical and Chemical Research |
|---|
Principal Investigator |
中村 健道 国立研究開発法人理化学研究所, 環境資源科学研究センター, 特別嘱託研究員 (10360611)
|
|---|
| Project Period (FY) |
2021-04-01 – 2024-03-31
|
| Keywords | tandem mass spectrometry / CID / isomerization / fragmentation pathway / ion structure / ion mobility / model chemistry |
|---|
| Outline of Annual Research Achievements |
Mass spectrometry is widely used in qualitative and/or quantitative analysis of organic compounds in many research fields; some of the emerging research fields such metabolomics solely rely on modern mass spectrometry as no other methods are sensitive enough for the available amounts of samples. However, structural identification of unknowns and known-unknowns is often a major bottleneck in those mass spectrometry-dependent research fields as the commonly used soft-ionization-based mass spectrometry provides rather limited amount of qualitative information. Fragmentation in collision-induced dissociation (CID) tandem mass spectrometry is analyzed for structural characterization beyond the molecular formula assignment of soft-ionized analytes including isomeric small molecules. However, not only the structural information obtainable in CID spectra is rather limited in many cases especially for very small molecules, it turned out the spectral information can be degraded due to isomerization prior to fragmentation. In order to analyze such isomerization and to understand the basis behind the chemistry, we established a test platform including energy-resolved tandem mass spectrometry, ion mobility spectrometry-tandem mass spectrometry, and computational model chemistry. Some isomeric small metabolites including C4 amino acids were chosen from a human metabolome database and used as test compounds for building and refining the analytical workflow.
|
| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
In the past fiscal year, we've mainly worked to refine and update the computational platform including hardware and software for the analysis of fragmentation chemistry and prediction and interpretation of ion mobility spectrometry data, as well. The computational modeling tools are tested and tuned for the larger scale extended study in the second and third year by using a limited number of chosen standard metabolites. Slight delay in the originally planned pilot-scale wet chemistry study was caused since we were unable to employ a student part-timer, who supposed to assist data collection and processing, due to the continued restrictive measures to decrease flow of people in the past year.
|
| Strategy for Future Research Activity |
In the next fiscal year, we continue to refine and extend computational analysis of fragmentation pathways including isomerization chemistries. It's a rather time consuming and painstaking process to deduce and identify key steps of the fragmentation chemistries including transition states of isomerization. In addition, structural assignment of isomerized product ions is not an easy task. However, it's absolutely necessary to address the chemistry basis for understanding the isomerization process better and to improve our ability to interpret data obtained by CID tandem mass spectrometry. To this end, for a limited number of selected model compounds in the metabolome database, we continue the cycle to build and refine model chemistry then validate/double-check the chemistry with experimental data including energy-resolved CID spectra and ion mobility spectrometry data, followed by re-building and refinement of the model chemistry, and so on.
|
| Causes of Carryover |
In the past fiscal year, we've rather focused on establishing and refining the computational platform for the analysis of model chemistry. As a result, the scale of wet chemical studies was cut down slightly and we've consumed less reagents and materials than originally planned for. In the next fiscal year, we expect to require more for reagents and materials to carry out experiments with standard metabolites, in addition to continue the enhancement and update of the computational part of the study as necessary. We also anticipate some amount to be spent for dissemination in the coming years.
|
Research Products
(1 results)
