Title

OXIDATION OF NUCLEIC ACIDS: CHEMISTRY OF PURINE QUINONES AND DEVELOPMENT OF NOVEL PHOTOOXIDIZING AGENTS

Date of Award

2010

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Photochemical Sciences

First Advisor

R. Marshall Wilson, PhD

Second Advisor

Neocles B. Leontis, PhD (Committee Member)

Third Advisor

Thomas H. Kinstle, PhD (Committee Member)

Fourth Advisor

Warren W. McGovern, PhD (Committee Member)

Abstract

Chemical behavior of the oxopurines 8-oxoadenosine and 8-oxoinosine has been investigated. Purine quinones, pivotal intermediates in oxidation of oxopurines were successfully trapped and the resulting products were characterized. Formation of purine quinones was demonstrated with both chemical and photochemical oxidizing agents. Adducts formed as a result of reaction of purine quinones with nucleophiles were isolated and characterized. Pyrene dihydrodioxins have been synthesized and shown to be effective agents for release of pyrene-4,5-dione. Pyrene-4,5-dione is an effective DNA photo-oxidation agent. Pyrene dihydrodioxin incorporating a pyridinium salt as a possible internal electron trap has been shown to release pyrenequinone rapidly. Dihydrodioxins containing two pyridine and pyridinium salt moieties have been synthesized and characterized by variety of methods including 1H and 13C NMR spectroscopy. Dihydrodioxin containing two pyridine moieties was separated into D and L enantiomers via liquid chromatography on a chiral sorbent. Affinities of D and L enantiomers of these dipyridinium pyrene dihydrodioxins for nucleic acids were compared.