Rationale Molecular dynamics (MD) simulations with finite temperature were performed to improve the theoretical prediction of collisional cross section (CCS) values, especially for aromatic compounds containing long alkyl chains. Methods In this study, the CCS values of 11 aromatic compounds with long alkyl chains were calculated by MD simulations while considering internal energy at 300, 500, and 700 K, and the results were compared with experimentally determined values. Results The CCS values calculated at higher energies showed better agreement with the experimental values. Polycyclic aromatic hydrocarbons (PAHs) such as pentacene and benz[b]anthracene were also investigated, and better agreement between the theoretical and experimental results was observed when higher temperature (or higher internal energy) was considered. Conclusions The data presented in this study show that the internal degrees of freedom of ions must be considered to accurately predict the CCS values of aromatic compounds with a flexible structure measured by ion mobility mass spectrometry.

Collisional cross section (CCS) values of a set of aromatic compounds were determined and the compounds were evaluated as standards for calibration and standardization. External calibration with poly-DL-alanine and internal and external calibration with the aromatic compounds were performed using the ion mobility mass spectra obtained from crude oils. The results showed that the external calibration method using the set of aromatic compounds is both accurate and easy to implement. The improved accuracy obtained using these aromatic standards can be explained by their greater structural similarity with the analytes in the crude oils. We anticipate that the adoption of these standards will increase the utility of IM-MS in petroleum analysis and make it easier to directly compare results from different studies.

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...