Author ORCID Identifier

https://orcid.org/0000-0002-8093-8941

Date of Award

12-16-2019

Degree Type

Closed Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Dr. Kathryn Grant

Second Advisor

Dr. David Wilson

Third Advisor

Dr. Gangli Wang

Abstract

This dissertation describes the study of anthracene/DNA interactions with the goal of simulating and understanding the conditions of high ionic strength similar to that of cell nucleus that a DNA photosensitizer might encounter (410 mM). The compounds used for studying the photocleavage reactions were bis 9-aminomethylanthracene dye 2 vs. a mono-anthracene 4, two 9-methylaminoanthracene derivatives. We observed that the addition of sodium and potassium chloride salts into photocleavage reactions containing micromolar concentrations of antharcene triggers the conversion of supercoiled, nicked, and linear forms of pUC19 plasmid into a highly degraded band of DNA fragments, representing a dramatic and unexpected increase in levels of anthracene-sensitized DNA photocleavage (KCl > NaCl; pH 7.0 and 22 °C). Experiments using specific ROS scavengers indicate higher levels of ROS production in presence of chloride salt. Further investigation into the mechanism of ROS production suggests more involvement of type I electron transfer in generation of hydroxyl radicals. In contrast to the chloride salts, anthracene-sensitized DNA photocleavage is inhibited (KI ≥ NaI ≥ KBr ≥ NaBr ≥ KF ≥ NaF). The results of CD spectroscopy suggest unwinding of DNA in presence of high concentration of potassium(I) salts and UV-visible absorption and fluorescence experiments point to the possibility of a heavy atom effect involving Br¯ and I¯ anions. DNA photocleavage and fluorescence probe experiments point to the involvement of photo-oxidized form of anthracene in ROS generation.

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