Ionization, dissociation, and the investigation of structure in small molecular models to develop a broader understanding of gas phase ion chemistry

This dissertation focuses on molecular systems in the low-mass range to determine how chemical and structural changes can affect subsequent fragmentation chemistry and protonation site. Each system was investigated using MS analysis and gas-phase ion structural techniques selected from tandem MS (MSMS), hydrogen-deuterium exchange (HDX), ion-mobility (IM), and action infra-red multi-photon dissociation (IRMPD).;In Chapter 3, the non-standard amino acid gamma-aminobutyric acid (GABA) was placed into a peptide system to test a mechanism which explained the lack of a3 ions in standard peptide fragmentations. GABA extends the peptide backbone by two methylene units and its insertion into the second position of larger peptides increases the intensity of a3 ion. Using MSMS, it was found that this was a result of blocking common favorable fragmentation pathways. The results demonstrated the use of modified peptides for revealing reasons for how peptides fragment.;Chapter 4 focused on a unique set of non-canonical amino acids and their ability to affect the trans/cis nature of adjacent amide bonds in peptide sequences. In solution, 4-R-Flouroproline (R-Flp) is found to favor the trans peptide bond and 4-S-fluoroproline (S-flp) favors the cis bond. IRMPD and IM-MS were employed to investigate the fragment ions containing these two prolyl-ring substitutions as the structures of the b2 ions might indicate the prevalence of cis vs. trans peptide bond in the gas-phase. In experiments, the residues favoring trans vs. cis bonds, respectively, formed greater proportions of the trans/cis fragment ions, showing a correlation between solution and gas-phase structural trends of peptides.;The two cancer drugs pomalidomide (Pom) and lenalidomide (Len) differ by the change of a single carbonyl functional group. Because these two drugs behave quite differently in vivo, the objective of Ch 5 to investigate their gas phase behavior using IRMPD, IM, and HDX, as differences in their gas-phase ion structures might shed light on their unique biological activities. From these techniques, it was determined that Pom alone possessed a clear amide-iminol tautomerization and the presence of multiple structures in its precursor and fragment ion populations.;The carotenoids alpha-carotene, beta-carotene, and lycopene are isobaric compounds, which differ in their ability to serve as precursors to vitamin A in vivo. Additionally their solution-state double-bond conformations influence their provitamin activity. The objective of Chapter 6 was to use IMS and MSMS to separate their radical ions to both quantify them without solution-phase separation and also to determine their pre-ionization trans/cis conformations. IM-MS provided reasonable relative quantification. Although the isomers gave different IM drift time distributions, even after activation, trans/cis conformation retention was not confidently ascertained.;In Chapter 7, high work-function metal oxides, ReO3 and WO 3 microparticles (muP) were tested as matrices for a number of small molecules encompassing protonation, sodiation, radical ionization, and pre-charged ablation. The particles' ability to ionize these compounds was compared with the standard matrix CCA. WO3 muP performed well for sodiated compounds while ReO3 muP worked well for protonated and radical species simultaneously. Moreover, ReO3 was less destructive of fragile ions compared to CCA at equivalent laser flux.