Ion/Ion Chemistry of High-Mass Multiply Charged Ions

Electrospray ionization has enabled the establishment of a new area of ion chemistry research based on the study of the reactions of high-mass multiply charged ions with ions of opposite polarity. The multiple-charging phenomenon associated with electrospray makes possible the generation of multiply charged reactant ions that yield charged products as a result of partial neutralization due to ion/ion chemistry. The charged products can be readily studied with mass spectrometric methods, providing useful insights into reaction mechanisms. This review presents the research done in this area, all of which has been performed within the past decade. Ion/ion chemistry has been studied at near-atmospheric pressure in a reaction region that leads to the atmospheric/vacuum interface of a mass spectrometer, and within a quadrupole ion trap operated with a bath gas at a pressure of 1 mtorr. Proton transfer has been the most common reaction type for high-mass ions, but other forms of "charge transfer," such as electron transfer and fluoride transfer, have also been observed. For some ion/ion reactions, attachment of the two reactants has been observed. Multiply charged ion/ion reactions are fast, due to the long-range Coulombic attraction, and they are universal in that any pair of oppositely charged ions is expected to react due to the high exothermicity associated with mutual neutralization. The kinetics of reaction for multiply charged ions, derived from the same molecule with a given singly charged reactant ion, follow a charge-squared dependence, at least under normal quadrupole ion trap conditions. This dependence suggests that reaction rates are determined by the long-range Coulomb attraction, and that the ions react with constant efficiency as a function of charge state. In the case of proton transfer reactions from polypeptides to even-electron perfluorocarbon anions, no fragmentation of the polypeptide product ions has, as yet, been observed. Electron transfer from small oligonucleotide anions to rare gas cations, on the other hand, results in extensive fragmentation of the nucleic acid product ions. The extent of fragmentation decreases as the size of the oligonucleotide anions increases, reflecting a decrease in fragmentation rates associated with an increase in the number of internal degrees of freedom of the oligonucleotide. When ion-cooling rates become competitive with dissociation rates, the initially formed product ions are stabilized and fragmentation is avoided. Collisional cooling, therefore, likely plays an important role in the relative lack of dissociation observed thus far as a result of ion/ion reactions for most high-mass ions. The observed dependence of ion/ion reaction rates on the square of the ion charge, the universal nature of mutual neutralization, and the relative lack of fragmentation that arises from ion/ion reactions, makes ion/ion chemistry a particularly useful means for manipulating charge states. This review emphasizes applications that take advantage of the unique characteristics of ion/ion proton transfer chemistry for manipulating charge states. These applications include mixture analysis by electrospray, precursor ion charge state manipulation for tandem mass spectrometry studies, and simplified interpretation of product ion spectra.