Comparison of Theoretical Calculation Methods for Obtaining Collisional Cross‐Section of Aromatic Compounds

Abstract

Mass spectrometry (MS) has emerged as one of the most important tools for chemical and biochemical analysis. 1 MS is widely used for the analysis of proteins, drugs, metabolites, petroleum products, environmental chemicals, and foods. In such studies, MS is used to measure the molecular weight of the compounds, which helps in identifying the molecules. In particular, ultrahigh resolution MS has been used to obtain accurate molecular weight. MS can also be used to elucidate chemical structures. In those application, tandem MS 2 and hydrogen-deuterium exchange MS have been used. 3-5 Ion mobility spectrometry-mass spectrometry (IMS-MS) 6-8 is another important method to study chemical structures and it is reported to be a promising research to study proteins, 9,10 metabolites, 11,12 and aromatic compounds in crude oil. 13 Gas-phase separation achieved by IM can add another level of chromatography to the commonly used liquid phase separation. 14-17 In addition, IM can be used to identify isomers.Despite its potential, the application of IM-MS has been limited in the MS community. There are two critical limitations of IM-MS analysis: (1) the limited resolving power for gas-phase separation; (2) the need for combining theoretical calculations. The former can be overcome by the development of suitable instruments and data interpretation methods. In the case of second limitation, it has been widely accepted that combining theoretical collisional cross-section (CCS) calculation with experimental determination of CCS is necessary to fully utilize the IM-MS data.The theoretical CCS calculation includes two steps: in the first step, the structures are calculated and optimized, and in the second step, the CCS was calculated based on the optimized structure. For structural optimization, quantum chemical approaches, including the density functional theory (DFT) 18 have been widely used. However, quantum mechanical calculations are computationally expensive and not suitable for regular users of IM-MS. Therefore, it will be advantageous for the IM-MS community if a less computationally expensive and more easily accessible classical method would be as effective as the quantum mechanical approach. However, the effectiveness of lower-level CCS calculation has not been evaluated.In this study, the theoretical CCS values determined by various theoretical calculations were compared with the experimentally determined CCS values. The overall work flow for a comparative study of the CCS values obtained by computational chemistry and MS measurement is presented in a previous study. Briefly, the CCS values of molecules are experimentally determined by IM-MS and then compared with the theoretically calculated CCS values to find structures that can best explain the obtained IM-MS spectra.The experimental CCS values were obtained from a previous work. 19 The list of compounds is provided in the Table S1 (Supporting Information). Briefly, the drift time is converted into the CCS based on the previously reported CCS values of poly-DL-alanine. 19...