The SMILES chemical identifier associated with each HMDB entry was used to generate the starting 2D-structure for the workflow. Using the cheminformatics toolbox RDKit , protonated, deprotonated and sodiated adduct ions were constructed by considering all nitrogen, oxygen and sulfur atoms as sites for H + or Na + addition or removal. This was done for all possible tautomers, after which resonance structures were filtered out. Some HMDB entries contained unspecified stereochemistry and were omitted, unless their stereochemistry would not affect the IR spectrum (enantiomers), in which case the stereochemistry was randomly assigned. For each ionized isomer a conformational search using RDKit's distance geometry algorithm was performed to produce 500 random 3D-conformations. After minimization using the MMFF94 classical force field, ten conformations were selected after clustering, or fewer if conformations were too similar (rms-deviation of atom positions <1.4 Å). The selected 3Dgeometries were then submitted to Gaussian16 for geometry optimization and frequency calculation at the semi-empirical PM6 level . Unfavorable ionization sites and unfavorable conformations were filtered by their relative energies (electronic + thermal) using a threshold of +40 kJ/mol from the global minimum. Additionally, geometries that converged to the same local minimum in the optimization were filtered based on their (nearly) identical vibrational spectrum. The remaining geometries were reoptimized using the B3LYP density functional and 6-311+G(d,p) basis set, followed by a frequency calculation. More accurate electronic energies at the MP2/6-311+G(d,p) level were calculated using the B3LYP geometry and combined with the thermal energy from the B3LYP frequency calculation.