Title

Photoaffinity Labeling Strategies Using Purine Nucleic Acid Bases

Date of Award

2011

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Photochemical Sciences

First Advisor

R. Marshall Wilson, Dr.

Second Advisor

Thomas H. Kinstle, Dr. (Committee Member)

Third Advisor

Robert M. McKay, Dr. (Committee Member)

Fourth Advisor

Alexander N. Tarnovsky, Dr. (Committee Member)

Abstract

Photodecomposition of 8-azidoadenosine and 8-azidoinosine has been studied by ultrafast transient absorption spectroscopy methods in different solvents, including water solutions with different pH values. The formation of two types of intermediates has been proposed their photodecomposition: diiminoquinone with an EDG on the purine ring, and iminonitriles in the absence of an EDG on the purine ring. Iminoquinone and iminonitrlies undergoes nucleophilic attack forming C2-adducts. Imidazole adduct, water adduct, reduction product, and ring destruction products has been isolated. Small amounts of dimer-like structures and other products have been detected, but have not been fully identified.

Synthesis of 6-azido-8-oxopurinoriboside has been performed for the first time. Photodecomposition of this azide has been studied by ultrafast transient absorption spectroscopy methods. The formation of iminoquinone as reactive intermediate has been proposed for photodecomposition of this azide in protic solvents. This iminoquinone leads to the formation of C2- and C6-adducts, and the reduction product. Imidazole adduct, 8-oxoadenosine , and 8-oxoinosine have been isolated and characterized from the reparative irradiation of 6-azido-8-oxopurinoriboside. Small amounts of other photodecomposition products have been detected, but have not been fully identified.