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

Abstract

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.

Gas-Phase Adsorption of N₂ on Protonated Molecules and Its Application to the Structural Elucidation of Small Molecules

“…The relationships between molecular structure and fragmentation have been studied using a variety of dissociation techniques. 3 , 4 ) Ion mobility and hydrogen/deuterium exchange have been used to analyze molecular structures. 5 , 6 ) Nuclear magnetic resonance spectroscopy of gas-phase ions using a magnetic resonance acceleration technique has been developed.…”

A tutorial in small molecule identification via electrospray ionization‐mass spectrometry: The practical art of structural elucidation

“…Therefore, this ion activation/fragmentation technique will be used in the examples discussed in this review. Electron‐based ion activation methods like electron capture/transfer dissociation are more commonly used for larger molecules such as peptides but can be also useful in certain small molecule applications, as was recently reviewed by Qi and Volmer …”

“…Electron-based ion activation methods like electron capture/transfer dissociation are more commonly used for larger molecules such as peptides but can be also useful in certain small molecule applications, as was recently reviewed by Qi and Volmer. 16 Several techniques can be applied to gain additional and orthogonal information that might lead to identification of the correct structure. The techniques discussed further in this tutorial are limited to those that are routinely coupled to mass spectrometry in the quest for the correct molecular structure.…”

Electron‐ion reaction‐based dissociation: A powerful ion activation method for the elucidation of natural product structures

“…These methods can induce the breakage of specific chemical bonds and the generation of distinct fragment ions. A number of review articles about ExD have been published following its development . However, most of the work focused on the application of the methods in protein/peptide characterization, and a review on their application to NPs is lacking.…”

“…A number of review articles about ExD have been published following its development. [26][27][28][29][30] However, most of the work focused on the application of the methods in protein/peptide characterization, and a review on their application to NPs is lacking. The present article provides an overview of the mechanisms, instrumentation, and typical applications related to ExD MS/MS in the structural characterization of NPs.…”