Infrared ion spectroscopy (IRIS) provides an alternative approach to molecular structure determination in MS. IRIS measures the IR spectrum of an m/z-selected population of ions in the MS instrument and thus provides detailed structural information . Being rooted in MS, IRIS can be appended to LC/MSworkflows , which has enabled its analytical implementation in, for instance, the identification of biomarkers for metabolic diseases and other small-molecule isomerism questions . Translation of an IR spectrum to a chemical structure is usually performed by formulating (a small number of) candidate structures based on prior knowledge of the underlying (bio)chemistry. Structural confirmation of these candidates is then achieved through comparison of the experimental IRIS spectrum to a reference spectrum from a physical standard and/or from a quantum-chemical prediction . The latter option enables identification without a physical reference standard and is therefore efficient if standards are not available. Density functional theory (DFT) calculations typically give accurate predictions of a compound's vibrational spectrum and have been employed in numerous fundamental ion chemistry studies utilizing IRIS . DFT-predictions are therefore useful for (preliminary) metabolite identification and can at least reduce the number of candidate structures substantially.