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theses

This dissertation focuses on the examination of thermochemical properties, including gas phase acidities, proton affinities and tautomerism of two types of N-heterocyclic organic species: damaged nucleobases and 1,2,3-triazoles via mass spectrometry methods (bracketing method on FTMS and Cooks kinetics method on LCQ) and theoretical studies (quantum mechanical calculations). Reactivities of N-heterocyclic carbenes as organocatalysts were also studied in the gas phase. 3-Methyladenine DNA glycosylase II (AlkA), which is found in Escherichia coli, is an enzyme that cleaves a wide range of damaged nucleobases from DNA. Herein we study the 3-methylated AlkA purine substrates, 3-methyladenine, non-substituted purine and and a potential AlkA substrate, 6-chloropurine. We found that the damaged nucleobases are more acidic than normal nucleobases. Resulting from this increasing of acidity, it is expected that damaged nucleobases are easier to be cleaved from the DNA chain since their conjugate bases should be better leaving groups. We also find that the gas phase acidities correlate with AlkA excision rate. Thus, the results lend support to the theory that AlkA differentiates among substrates by cleaving those nucleobases which are the most facile to remove. We also focus on studying the gas phase properties of 1,2,3-triazoles, which, compared with their applications, are largely unknown. The gas phase acidities and proton affinities of benzotriazole, 4-phenyl-1,2,3-triazole, substituted 4-phenyl-1,2,3-triazoles are discussed herein. Moreover, the tautomerism prevalence of 4-phenyl-1,2,3-triazole is acertained by ion-molecule reaction coordinate analysis and H/D exchange studies. In order to study the reaction mechanism of N-heterocyclic carbenes catalyzed reactions such as benzoin condensation, we synthesized a thiazolium catalyst with ethyl sulfonyl group on C4 position of five-membered thiazolium ring. Upon deprotonation, the thiazolium-based carbene is given a negative charge, which renders the visibility for both the carbene and reaction intermediates via mass spectrometry. We herein isolate and study the fragmentation pattern of both free carbene and reaction intermediates using ESI-MS/MS technique. As comparison, we also employ an imidazolium-based NHC to study the benzoin condensation via mass spectrometry and characterize the catalyst as well as the intermediates.

ETD_5510

Ph.D.

Includes bibliographical references

by Kai Wang

doi:10.7282/T3H993H7

ETD doctoral

The author owns the copyright to this work.