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.