Ab initio molecular dynamics calculations on electron ionization induced fragmentations of C4F7N and C5F10O for understanding their decompositions under discharge conditions.

C4F7N and C5F10O are the most promising SF6 alternatives as eco-friendly insulating gaseous mediums in electrical engineering. It is necessary to clarify their electrical stability and decomposition mechanisms. In this work, we first introduced our experimental results for decomposition products of C4F7N/CO2 and C5F10O/synthetic air mixtures under partial discharge and spark discharge conditions. Then, we performed ab initio molecular dynamics (AIMD) simulations on the typical decomposition products. The simulations were performed under standard electron impact mass spectrometry (EI-MS); thus, the statistical results of the mass spectra were compared with those of the experimentally obtained standard mass spectra from the NIST database. The AIMD simulation method in simulating the electron-induced ionization process was verified and found to be reliable. Finally, the calculations were also performed for C4F7N and C5F10O with incident electron energies of 20 eV and 70 eV, respectively. The dominant pathway for both gases is the formation of CF3+ with the fracture of the C-C bond. The AIMD simulation is able to predict the decomposition channels after electron-impact ionization without any preconceived knowledge of fragmentation pathways, which provides a novel insight into understanding the decomposition mechanisms of C4F7N and C5F10O under different discharge conditions with different energies.

Quantum Chemistry-based Molecular Dynamics Simulations as a Tool for the Assignment of ESI-MS/MS Spectra of Drug Molecules.

In organic mass spectrometry, fragment ions provide important information on the analyte as a central part of its structure elucidation. With increasing molecular size and possible protonation sites, the potential energy surface (PES) of the analyte can become very complex, which results in a large number of possible fragmentation patterns. Quantum chemical (QC) calculations can help here, enabling the fast calculation of the PES and thus enhancing the mass spectrometry-based structure elucidation processes. In this work, the previously unknown fragmentation pathways of the two drug molecules Nateglinide (45 atoms) and Zopiclone (51 atoms) were investigated using a combination of generic formalisms and calculations conducted with the Quantum Chemical Mass Spectrometry (QCxMS) program. The computations of the de novo fragment spectra were conducted with the semi-empirical GFNn-xTB (n=1, 2) methods and compared against Orbitrap measured electrospray ionization (ESI) spectra in positive ion mode. It was found that the unbiased QC calculations are particularly suitable to predict non-evident fragment ion structures, sometimes contrasting the accepted generic formulation of fragment ion structures from electron migration rules, where the "true" ion fragment structures are approximated. For the first time, all fragment and intermediate structures of these large-sized molecules could be elucidated completely and routinely using this merger of methods, finding new undocumented mechanisms, that are not considered in common rules published so far. Given the importance of ESI for medicinal chemistry, pharmacokinetics, and metabolomics, this approach can significantly enhance the mass spectrometry-based structure elucidation processes and contribute to the understanding of previously unknown fragmentation pathways.

Calculation of Mass Spectra with the QCxMS Method for Negatively and Multiply Charged Molecules.

Analysis and validation of a mass spectrometry (MS) experiment are usually performed by comparison to reference spectra. However, if references are missing, measured spectra cannot be properly matched. To close this gap, the Quantum Chemical Mass Spectrometry (QCxMS) program has been developed. It enables fully automatic calculations of electron ionization (EI) and positive ion collision-induced dissociation (CID) mass spectra of singly charged molecular ions. In this work, the extension to negative and multiple ion charge for the CID run mode is presented. QCxMS is now capable of calculating structures carrying any charge, without the need for pretabulated fragmentation pathways or machine learning of database spectra. Mass spectra of four single negatively charged and two multiple positively charged organic ions with molecular sizes from 12 to 92 atoms were computed and compared to reference spectra. The underlying Born-Oppenheimer molecular dynamics (MD) calculations were conducted using the semiempirical quantum mechanical GFN2-xTB method, while for some small molecules, ab initio DFT-based MD simulations were performed. Detailed insights into the fragmentation pathways were gained, and the effects of the computed charge assignments on the resulting spectrum are discussed. Especially for the negative ion mode, the influence of the deprotonation site to create the anion was found to be substantial. Doubly charged fragments could successfully be calculated fully automatically for the first time, while higher charged structures introduced severe assignment problems. Overall, this extension of the QCxMS program further enhances its applicability and underlines its value as a sophisticated toolkit for CID-based tandem MS structure elucidation.

From QCEIMS to QCxMS: A Tool to Routinely Calculate CID Mass Spectra Using Molecular Dynamics.

Mass spectrometry (MS) is a powerful tool in chemical research and substance identification. For the computational modeling of electron ionization MS, we have developed the quantum-chemical electron ionization mass spectra (QCEIMS) program. Here, we present an extension of QCEIMS to calculate collision-induced dissociation (CID) spectra. The more general applicability is accounted for by the new name QCxMS, where "x" refers to EI or CID. To this end, fragmentation and rearrangement reactions are computed "on-the-fly" in Born-Oppenheimer molecular dynamics (MD) simulations with the semiempirical GFN2-xTB Hamiltonian, which provides an efficient quantum mechanical description of all elements up to Z = 86 (Rn). Through the explicit modeling of multicollision processes between precursor ions and neutral gas atoms as well as temperature-induced decomposition reactions, QCxMS provides detailed insight into the collision kinetics and fragmentation pathways. In combination with the CREST program to determine the preferential protonation sites, QCxMS becomes the first standalone MD-based program that can predict mass spectra based solely on molecular structures as input. We demonstrate this for six organic molecules with masses ranging from 159 to 296 Da, for which QCxMS yields CID spectra in reasonable agreement with experiments.

Predicting the Mass Spectra of Environmental Pollutants Using Computational Chemistry: A Case Study and Critical Evaluation.

Organic pollutants can be identified by comparing their electron ionization (EI) mass spectra with those in libraries or obtained from authentic standards. Nevertheless, libraries are incomplete; standards may be unavailable or too costly, or their synthesis may be too time-consuming. This study evaluates the performance of quantum chemical electron ionization mass spectrometry (QCEIMS) vis-à-vis competitive fragmentation modeling (CFM) for suspect screening and unknown identification. EI mass spectra of 35 compounds, including halogenated organics, organophosphorus flame retardants (OPFRs), and disinfection byproducts were computed. Computational results were compared with EI mass spectra compiled in the NIST Library as well as collision-induced dissociation (CID) mass spectra obtained from radical cations M•+ generated by charge-exchange atmospheric pressure chemical ionization (APCI). The results indicate that QCEIMS performs equivalently or better than CFM. Average match factors between computed and experimental (NIST) EI mass spectra were 656 vs 503 for the halogenated organics, and on average, QCEIMS predicted 55% of the products generated by CID vs 17% predicted by CFM. QCEIMS predicted 37% of the OPFR CID products whereas CFM predicted 29%. QCEIMS performed comparably to a commercial combinatorial fragmentation method for suspect screening of a dust sample, identifying 19/20 targets. Examples of unknown pollutants, whose reference spectra were unavailable at the time of discovery, are also presented. The computational results suggest that QCEIMS can help guide the analyst in obtaining authentic standards and raise the possibility that, with advances in computing, an unknown may eventually be confirmed in hours as opposed to the days or months required to obtain authentic standards.

Calculation of Electron Ionization Mass Spectra with Semiempirical GFNn-xTB Methods.

In this work, we have tested two different extended tight-binding methods in the framework of the quantum chemistry electron ionization mass spectrometry (QCEIMS) program to calculate electron ionization mass spectra. The QCEIMS approach provides reasonable, first-principles computed spectra, which can be directly compared to experiment. Furthermore, it provides detailed insight into the reaction mechanisms of mass spectrometry experiments. It sheds light upon the complicated fragmentation procedures of bond breakage and structural rearrangements that are difficult to derive otherwise. The required accuracy and computational demands for successful reproduction of a mass spectrum in relation to the underlying quantum chemical method are discussed. To validate the new GFN2-xTB approach, we conduct simulations for 15 organic, transition-metal, and main-group inorganic systems. Major fragmentation patterns are analyzed, and the entire calculated spectra are directly compared to experimental data taken from the literature. We discuss the computational costs and the robustness (outliers) of several calculation protocols presented. Overall, the new, theoretically more sophisticated semiempirical method GFN2-xTB performs well and robustly for a wide range of organic, inorganic, and organometallic systems.