The emerging role of ion/ion reactions in biological mass spectrometry: considerations for reagent ion selection.

The advent of ionization methods that can produce multiply charged gaseous ions has enabled the development of gas-phase ion/ion reactions in analytical mass spectrometry. Ion/ion chemistry has proved to be a particularly effective means for converting ions from one type to another and allows for a decoupling of the ionization method from the nature of the ion subjected to tandem mass spectrometry. A growing array of applications has been developed based on a variety of reaction types, including electron transfer, proton transfer, charge inversion, metal transfer, etc. Most ion/ion reactions take place following the formation of a stable bound orbit between the reactants. As reactants approach closely enough for chemistry to occur, they can react by small charged particle transfer (i.e. electron transfer and proton transfer) at crossing points in the interaction potential. Alternatively, the reactants can collide to form a relatively long-lived complex. A wide range of chemical reactions can result from the long-lived complex, which include multiple charged particle transfers and covalent bond formation. For a given analyte ion, the major reaction pathway is determined by the characteristics of the reagent ion. An appreciation of the factors that underlie the partitioning of ion/ion reaction products is important in the design and selection of reagent ions to effect transformations of interest. Important considerations for reagent ion selection are discussed here within the context of a generalized scheme for ion/ion reaction dynamics.