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Understanding of protomers/deprotomers by combining mass spectrometry and computation

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Abstract

Multifunctional compounds may form different prototropic isomers under different conditions, which are known as protomers/deprotomers. In biological systems, these protomer/deprotomer isomers affect the interaction modes and conformational landscape between compounds and enzymes and thus present different biological activities. Study on protomers/deprotomers is essentially the study on the acidity/basicity of each intramolecular functional group and its effect on molecular structure. In recent years, the combination of mass spectrometry (MS) and computational chemistry has been proven to be a powerful and effective means to study prototropic isomers. MS-based technologies are developed to discriminate and characterize protomers/deprotomers to provide structural information and monitor transformations, showing great superiority than other experimental methods. Computational chemistry is used to predict the thermodynamic stability of protomers/deprotomers, provide the simulated MS/MS spectra, infrared spectra, and calculate collision cross-section values. By comparing the theoretical data with the corresponding experimental results, the researchers can not only determine the protomer/deprotomer structure, but also investigate the structure–activity relationship in a given system. This review covers various MS methods and theoretical calculations and their devotion to isomer discrimination, structure identification, conformational transformation, and phase transition investigation of protomers/deprotomers.

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Funding

This work was financially supported by the National Key R&D Program of China (No. 2021YFA1501201) and the National Natural Science Foundation of China (No. 21874153). The authors acknowledge support from State Key Laboratory of Heavy Oil Processing, China University of Petroleum-Beijing.

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  1. State Key Laboratory of Heavy Oil Processing, College of Chemical Engineering and Environment, China University of Petroleum-Beijing, Beijing, 102249, People’s Republic of China

    Dali Fu, Sara Girmay Habtegabir, Haodong Wang, Shijie Feng & Yehua Han

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  1. Dali Fu
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  2. Sara Girmay Habtegabir
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  3. Haodong Wang
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Correspondence to Yehua Han.

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Published in the topical collection Young Investigators in (Bio-)Analytical Chemistry 2023 with guest editors Zhi-Yuan Gu, Beatriz Jurado-Sánchez, Thomas H. Linz, Leandro Wang Hantao, Nongnoot Wongkaew, and Peng Wu.

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Fu, D., Habtegabir, S.G., Wang, H. et al. Understanding of protomers/deprotomers by combining mass spectrometry and computation. Anal Bioanal Chem 415, 3847–3862 (2023). https://doi.org/10.1007/s00216-023-04574-1

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