The use of in silico IR spectra as a spectral reference enables us to attribute normal mode vibrations of specific functional groups to each band in the spectrum. This allows spectral mismatches to be correlated with structural mismatches. For example, in Figure , the computed bands in the 900-1050 cm -1 range originate from bending vibrations of the aldehyde C-H and the -hydroxide O-H. Likewise, the band at 1600 cm -1 in Figure corresponds to the C-O -stretch of the phenoxide. In cases where the actual metabolite is not included in the library, this may suggest new structures based on correctly and incorrectly matching substructure(s). Computing IR spectra for these newly conceived structures is then a route towards de novo structure identification of unknown unknowns (i.e., compounds that are not contained in the IR spectral library).