Structural analysis of small to medium-sized molecules by mass spectrometry after electron-ion fragmentation (ExD) reactions

Electron capture dissociation (ECD) is a tandem mass spectrometry (MS/MS) method that utilizes the interaction of ions and electrons. Its unique ability to preserve labile bonds distinguishes it from conventional threshold-based MS/MS methods, the most important of which is collision-induced dissociation (CID). During the last decade, ECD has opened up several new venues in protein analyses, for example top-down sequencing, identification of post-translational modifications, and characterization of protein–protein interactions. In recent years, a number of related dissociation techniques, so-called ExD techniques, particularly electron transfer dissociation (ETD), electron detachment dissociation (EDD), electron induced dissociation (EID), and negative electron transfer dissociation (NETD), have emerged and have extended the application range of ion-electron dissociations further. Importantly, ExD techniques have been applied beyond protein analyses, which is the focus of the current paper. This short introduction describes the application of ExD to small and medium-sized molecules and reviews important applications to natural products, biomedical compounds, synthetic molecules, crude oils, and environmental toxins.