Collision-induced isomerization in tandem mass spectrometry

2022 Fiscal Year Research-status Report

• 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 / isomerization / fragmentation pathway / ion structure / ion mobility / model chemistry / energetics

Outline of Annual Research Achievements

Collision-induced dissociation (CID) is widely available method for obtaining structural information with tandem mass spectrometry (MS2). Multiple-collision conditions under low-energy regime are the most commonly used experimental setup and implemented most of the modern tandem mass spectrometers. It's an easy and sensitive method, however, low-energy CID give rather limited structural information; MS2 spectral patterns tend to become rather simple for small molecules and spectral patterns of isomers may become indistinguishable as viable fragmentation pathways are rather limited. Such isomers could be differentiated by using our energy-resolved (ER) MS2 strategy as breakdown diagrams are sensitive to the changes in energetics of fragmentation chemistry caused by subtle structural differences between each isomers. In addition to the change in energetics, isomerization process of precursor ions may be hidden in the CID process. For example, a computer modeling study on CID process of ortho- and para-isomers of coumaric acid, which show common CO2 loss, suggested that fragmentation of para-isomer involves isomerization of [M-H]- to a key intermediate for the CO2 loss. The proposed fragmentation mechanism including the isomerization process was supported by the energetics, which was consistent to the data obtained by ER-MS2 experiments.

Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

In the last fiscal year, unfortunately, the level of our wet-lab experimental activity had still been kept lower than usual. We needed to keep our focus rather on the computational studies. In addition, we needed to replace a couple of old mass spectrometers in the middle of last year so that we can make a room in our lab to install a new shared instrument in our organization. The new shared instrument has a capability of a high-resolution ion mobility separation so that we can take advantage of it in this research project. Although we needed to wait for a few months until the new machine to be installed, the machine became operational at the end of the last fiscal year.

Strategy for Future Research Activity

Now the new shared instrument become operational, we accelerate the wet-lab experiments to catchup by taking advantage of the superior resolving power in ion mobility experiments. We will further identify and characterize isomerization associated with low-energy CID processes. In addition, we combine and organize energy-resolved CID MS2 and ion mobility experimental data with the accumulated results of computational studies so that we can finalize and disseminate the outcome of the research project in the final year.

Causes of Carryover

In the last fiscal year, we've been rather focusing on computational model studies so that we've consumed less reagents and materials than originally planned for. In the meantime, as the social environment has continued to be rather restrictive for real scientific meetings through most of the year, we postponed the plans for attending meetings to the final year. In the final year, we also expect to require more for reagents and materials to carry out experiments to catchup. In addition, we also anticipate some amount to be spent for dissemination of the outcome of the research project.