Turecek, FrantisekHuang, Shu Rong2021-08-262021-08-262021-08-262021Huang_washington_0250E_22837.pdfhttp://hdl.handle.net/1773/47395Thesis (Ph.D.)--University of Washington, 2021This dissertation reports the UV/Vis spectroscopic investigations of transient DNA cation radical intermediates generated from collision-induced dissociation and electron transfer dissociation. To generate cation radicals using collision-induced dissociation, doubly-charged ternary Cu(II) complexes with auxiliary ligand 2,2’;6’,2’’-terpyridine and a DNA nucleobase were first formed via electrospray ionization and upon collision-induced dissociation, the ternary Cu(II) complexes undergo intramolecular redox reaction and oxidize the nucleobase to generate the DNA cation radical. To generate the cation radical using electron transfer dissociation, a doubly-charged single-strand DNA sequence was first generated via electrospray ionization and upon electron-transfer dissociation, the one electron charge-reduction will generate the DNA cation radical containing an extra hydrogen adduct. These two methods approximate the mechanism on how these DNA cation radicals are suspected to be generated in nature via ionization. Briefly, the first method of utilizing the collision-induced dissociation with ternary Cu(II) complexes represents the direct ionization of DNA. The second method of utilizing electron-transfer dissociation on multiply-charged DNA represents the indirect ionization of DNA. This dissertation covers five projects involving these radical species. The first project discusses the collision-induced dissociation of the ternary Cu(II)-2,2’;6’,2’’-terpyridine-adenine complex to oxidize the adenine nucleobase. This spectroscopy investigation reveals the canonical 9-methyladenine cation radical is the dominant tautomer upon direct ionization of the nucleobase. Our high-level ab initio calculations also reveal the more stable 9-methylene-(1H)-adenine cation radical; unfortunately, this lower energy tautomer was not observed in the experimental action spectrum. As a follow-up, the second project is a targeted synthesis to generate the 9-methylene-(1H)-adenine tautomer. This elusive tautomer, generated in the gas-phase, also exhibited interesting gas-phase chemistry, where the primary dissociation proceeded with a hydrogen loss and a rearrangement to yield a protonated aminopteridine ion as the product. With deuterium labeling, reaction energetics and reaction kinetics, we propose an indirect mechanism for this rearrangement. The third and fourth projects report the generation of the hachimoji DNA cation radicals from collision-induced dissociation of the Cu(II) ternary complexes. This investigation revealed that the canonical tautomers are formed upon intramolecular electron transfer for the two synthetic purine nucleobases, isoguanine and 5-aza-7-deazaguanine. The two synthetic pyrimidine nucleobases, however, offer different gas-phase chemistry from each other. Based on the action spectrum and our ab initio calculations on the 6-amino-5-nitro-(1H)-pyrid-2-one cation radical, we concluded that the canonical structure is the dominant form produced upon electron transfer. For 1-methylcytosine, oxidation was accompanied by isomerization of the canonical tautomer to form 1-methylene-2-hydroxy-4-aminopyrimidine cation radical as the dominant ion, as revealed by the action spectrum, our density functional theory calculations, and deuterium exchange experiments. The last project discusses the one-electron transfer to a doubly-charged single strand DNA, GATC, to generate the cation radical moiety. The experimental spectrum and our density functional theory calculations reveal the cation radical isomerizes to a new 7,8-H-dihydroguanine cation radical.application/pdfen-USnoneAnalytical chemistryChemistryThesis