Selective gas phase ion-molecule reactions of biologically active lactones and lactams

Mass spectrometric techniques are used to investigate selective gas-phase ion-molecule reactions of biologically active lactones and lactams. A systematic procedure for exploring the selectivity is used since the target molecules have multiple potentially reactive sites. The bimolecular and dissociation reactions of model compounds representing components of the complex molecules are characterized first. Then the reactivity of the multifunctional compounds is evaluated to determine whether each of the components is represented, or whether certain functional groups dominate the molecule's reactivity as a whole or interact with other groups to cause modifications in reactivity.;Simple lactones, which are important sub-units of many biologically active natural products and antibiotics, are protonated and methylated by dimethyl ether ions, and the dissociation reactions of the methylated lactones allow differentiation of two groups of lactones based on ring size and substitution patterns. Next, the reactivity of dimethyl ether ions with a slightly more complex lactone, a pyrrole lactone, is investigated. The pyrrole ring, rather than the lactone ring, guides the bimolecular reactions, while the lactone ring dominates the dissociation reactions of the protonated pyrrole lactone. Thus, bimolecular and dissociation reactions provide complementary information. The selective ion-molecule reactions of dimethyl ether ions and biological lactones such as sugar lactones and ascorbic acid demonstrate their utility for distinguishing isomers.;The bimolecular and dissociation reactions of small lactams, both unsubstituted and with methyl substituents in various positions, are also characterized because they are important structural components of 1,4-benzodiazepines, the ultimate target class of compounds in this thesis. The unique ion-molecule reactions of lactams with dimethyl ether ions provides a means to differentiate N-methyl substituted lactams from C-methyl substituted and unsubstituted lactams. The products formed by ion-molecule reactions of 1,4-benzodiazepines and dimethyl ether ions reflect competitive reaction pathways leading to structurally diagnostic products, and dissociation reactions of various reaction products supply additional information. A comparison of the reactions of l,4-benzodiazepines and model compounds indicates that the reactive site is dependent on subtle structural features, so the reaction products are indicative of small structural details of the 1,4-benzodiazepines.