Ion/neutral, ion/electron, ion/photon, and ion/ion interactions in tandem mass spectrometry: do we need them all? Are they enough?

Abstract

A range of strategies and tools have been developed to facilitate the determination of primary structures of analyte molecules of interest via tandem mass spectrometry (MS/MS). The two main factors that determine the primary structural information present in an MS/MS spectrum are the type of ion generated from the analyte molecule and the dissociation method. The ion type subjected to dissociation is determined by the ionization method/conditions and ion transformation processes that might take place after initial gas-phase ion formation. Furthermore, the range of analyte-related ion types can be expanded via derivatization reactions prior to mass spectrometry. Dissociation methods include those that simply alter the population of internal states of the mass-selected ion (i.e., activation methods like collision-induced dissociation) as well as processes that rely on the transformation of the ion type prior to dissociation (e.g., electron capture dissociation). A variety of ion interactions have been studied for the purpose of ion dissociation and ion transformation, including ion/neutral, ion/photon, ion/electron, and ion/ion interactions. A wide range of phenomena have been observed, many of which have been explored/developed as means for structural analysis. The techniques arising from these phenomena are discussed within the context of the elements of structural determination in tandem mass spectrometry: ion-type definition and dissociation. Unique aspects of the various ion interactions are emphasized along with any barriers to widespread implementation.

Figure 1

Product ion spectra from the dissociation of various doubly-charged ion-types of native somatostatin: a) ion trap CID of the (M+2H)²⁺ ion, b) ion trap CID of the (M-2H)²⁻ ion, c) ion trap CID of the (M+Au+H)²⁺ ion produced in the gas phase from (M+3H)³⁺ via reaction with AuCl₂⁻ (Δ symbol represents internal fragments from within the loop defined by the disulfide bridge that result from two consecutive amide bond cleavages, the * indicates the presence of Au⁺ in the fragment, and (a) and (b) represent structures proposed in the original paper (see reference [6]), and d) ETD of the (M+3H)³⁺ ion (which leads to dissociation of the (M+3H)^2+•).

Figure 2

Schematic picture depicting selection of ion-type and dissociation method for structural characterization in tandem mass spectrometry. Note that some dissociation methods may not be compatible with all ion types. M represents a molecule of interest. 𝚳 and 𝓂 represent intentionally modified forms of M. Modifications might be made for one or more reasons, such as to facilitate quantitation, ionization, and/or fragmentation.