Ion/Ion reactions in the gas-phase have been shown to be very useful in the analysis of large biomolecules such as proteins, DNA and RNA. Specifically, these ion/ion reactions have been used to charge reduce a population of protein ions within a mixture, which makes identification of the mixture components more facile. The ability to invert the polarity of a protein or peptide analyte within the mass spectrometer enables the ionization polarity of an analyte to be separated from the analysis polarity of an analyte. One advantage to charge inverting an analyte species is that it can allow tandem mass spectrometry data to be obtained from the analyte in both polarities, which will provide complementary structural information from the analyte. Most ion/ion reactions were initially performed on 3D ion trap instruments, which can trap opposite polarity ions simultaneously within the ion trap allowing ion/ion reactions. However, these 3D ion traps have the disadvantage of low trapping efficiencies and low ion storage volumes. Linear ion trap or 2D ion traps were recently developed for ion/ion reactions and have the advantage of higher trapping efficiencies and higher ion storage volumes than the 3D ion traps, which has made linear ion traps the preferred instrument for ion/ion reactions. The work presented in this thesis has furthered the development of reagents for negative to positive charge inversion of peptides within 3D and 2D ion traps as well as furthered the development of new methods for ion/ion reactions in RF only regions of 2D ion trap instruments.

The initial part of this dissertation involves the investigation of both multiply charged proteins and dendrimer ions as negative to positive charge inversion reagents for the deprotonated peptide bradykinin. It was determined in this first work that the amino acid composition of peptides influenced the negative to positive charge inversion characteristics of peptides, and further work examined this phenomenon in detail. Methods were also developed for performing both charge inversion and charge reduction ion/ion reactions within the RF only Q0 quadrupole of a linear ion trap. It was determined that the use of the Q0 quadrupole for ion/ion reactions was both efficient and provided a means of performing sequential ion/ion reactions within a linear ion trap, extending the analytical capabilities of the linear trap. Lastly, a new triple ion source which contains two electrospray ionization sources and a matrix assisted laser desorption ionization source was characterized for ion/ion reactions within a linear ion trap.