Beyond the Ground State: Predicting Electron Ionization Mass Spectra Using Excited-State Molecular Dynamics

Here, we provide an algorithm that introduces excited states into the molecular dynamics prediction of the 70 eV electron ionization mass spectra. To decide the contributions of different electronic states, the ionization cross section associated with relevant molecular orbitals was calculated by the binary–encounter–Bethe (BEB) model. We used a fast orthogonalization model/single and double state configuration interaction (OM2/CISD) method to implement excited states calculations and combined this with the GFN1-xTB semiempirical model. Demonstrated by predicting the mass spectrum of urocanic acid, we showed better accuracies to experimental spectra using excited-state molecular dynamics than calculations that only used the ground-state occupation. For several histidine pathway intermediates, we found that excited-state corrections yielded an average of 73% more true positive ions compared to the OM2 method when matching to experimental spectra and 16% more true positive ions compared to the GFN method. Importantly, the exited state models also correctly predict several fragmentation reactions that were missing from both ground-state methods. Overall, for 48 calculated molecules, we found the best average mass spectral similarity scores for the mixed excited-state method compared to the ground-state methods using either cosine, weighted dot score, or entropy similarity calculations. Therefore, we recommend adding excited-state calculations for predicting the electron ionization mass spectra of small molecules in metabolomics.