A comparison of the reactions of a sigma-monoradical in solution and gas phase and the evaluation of isomer detection in gas-phase data analysis
The reactivity of carbon-centered sigma-monoradicals is an important area of study in chemistry. Of particular interest is their reactivity toward DNA components since some naturally occurring enediyne anti-tumor drugs form a carbon-centered sigma,sigma-biradical intermediate that causes irreversible damage to double stranded DNA. A greater understanding of the reactivities of related monoradicals must be obtained before the reactivities of the biradical intermediates can be addressed. Mass spectrometry has been used to study the reactions of nucleobases with various charged radicals in the past. The gas-phase environment in the mass spectrometer allows the reactions to occur without competing reactions with solvent molecules so that only the molecules of interest are involved. However, since drug reactions in a cell do not occur in a gaseous environment, a direct comparison of gas-phase and solution results would be valuable. This dissertation discusses ion-molecule reactions of charged monoradicals occurring in both gas phase and solution. The differences in reactivity in the two environments are rationalized by solvent effects, such as hydrogen bonding interactions between the DNA components and solvent molecules and solvent caging, as well as apparent differences in conformation of larger DNA components in gas phase and solution. The gas-phase reactivities of some charged bi- and triradicals toward simple organic reagents were examined in a FT-ICR mass spectrometer. The reactivities can be rationalized by previously reported reactivity controlling factors, such as the electron affinity of the radical site, the extent of coupling between biradical electrons and hydrogen bonding interactions in the transition state. The reactivities of two charged para-benzyne analogs appear to be most strongly controlled by differences in the electron affinities of the radical sites. When the electrophilicity (i.e., calculated electron affinity) increases, the transition state becomes more polarized, resulting in faster radical reactions. In contrast, comparison of the reactivity of a pyridine-based triradical to previously reported results for three related triradicals suggests that its reactivity is predominantly controlled by the extent of coupling between the radical electrons. During reactions, a radical may isomerize. Each isomer may react through separate pathways and at different efficiencies. In mass spectrometry, ionized isomers cannot be isolated to examine their properties separately. The potential for multiple isomers complicates the interpretation of the results of reactivity studies. In general, the presence of two isomers with different reaction efficiencies can be distinguished based on semi-logarithmic reaction rate plots that deviate from linearity. As the two efficiencies approach equality, the semi-logarithmic plot approaches linearity, which implies the presence of only a single isomer. Model data were used to determine the point at which curve fitting software finds a line instead of a curve, thus indicating the practical limits of finding multiple isomers by using a curve fitting method.^
Hilkka I. Kenttamaa, Purdue University.