Calculation of mass spectra with the QCxMS method for negatively and multiply charged molecules

Detailed information about the structural composition of an unknown chemical analyte can be obtained routinely and reliably by using mass spectrometry (MS). Analysis and validation of an MS experiment are usually performed by comparison to reference spectra, which are stored in databases that contain a large number of entries for common molecules. This procedure relies on the quality and completeness of the entries and if structures (classes) are missing, measured spectra cannot be properly matched. To close this gap, and to enable detailed mechanistic analysis, the Quantum Chemical Mass Spectrometry (QCxMS) program has been developed. It enables fully automatic calculations of electron ionization (EI), dissociative electron attachment (DEA), 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 pre-tabulated fragmentation pathways or machine-learning of database spectra. Mass spectra of four single negatively charged, as well as two multiple positively charged organic ions with molecular sizes ranging from 12 to 92 atoms were computed and compared to reference spectra taken from the literature. The underlying Born-Oppenheimer molecular dynamics (MD) calculations were conducted using the extended tight-binding semi-empirical 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 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.