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 multipl y charged ions with ions of opposite polarity. The multiple-charging phenom enon associated with electrospray makes possible the generation of multiply charged reactant ions that yield charged products as a result of partial n eutralization due to ion/ion chemistry. The charged products can be readily studied with mass spectrometric methods, providing useful insights into re action 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 t o the atmospheric/vacuum interface of a mass spectrometer, and within a qua drupole 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 oth er forms of "charge transfer," such as electron transfer and fluoride trans fer, have also been observed. For some ion/ion reactions, attachment of the two reactants has been observed. Multiply charged ion/ion reactions are fa st, due to the long-range Coulombic attraction, and they are universal in t hat any pair of oppositely charged ions is expected to react due to the hig h exothermicity associated with mutual neutralization. The kinetics of reac tion 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 tha t the ions react with constant efficiency as a function of charge state. In the case of proton transfer reactions from polypeptides to even-electron p erfluorocarbon anions, no fragmentation of the polypeptide product ions has , as yet, been observed. Electron transfer from small oligonucleotide anion s to rare gas cations, on the other hand, results in extensive fragmentatio n of the nucleic acid product ions. The extent of fragmentation decreases a s the size of the oligonucleotide anions increases, reflecting a decrease i n fragmentation rates associated with an increase in the number of internal degrees of freedom of the oligonucleotide. When ion-cooling rates become c ompetitive with dissociation rates, the initially formed product ions are s tabilized and fragmentation is avoided. Collisional cooling, therefore, lik ely plays an important role in the relative lack of dissociation observed t hus far as a result of ion/ion reactions for most high-mass ions. The obser ved dependence of ion/ion reaction rates on the square of the ion charge, t he universal nature of mutual neutralization, and the relative lack of frag mentation that arises from ion/ion reactions, makes ion/ion chemistry a par ticularly useful means for manipulating charge states. This review emphasiz es applications that take advantage of the unique characteristics of ion/io n proton transfer chemistry for manipulating charge states. These applicati ons include mixture analysis by electrospray, precursor ion charge state ma nipulation for tandem mass spectrometry studies, and simplified interpretat ion of product ion spectra. (C) 1999 John Wiley & Sons, Inc.