Date of Award

Fall 9-23-2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Dr. Kathryn B. Grant

Abstract

The interaction of small molecules with DNA has been extensively studied and has produced a large catalogue of molecules that non-covalently bind to DNA though groove binding, intercalation, electrostatics, or a combination of these binding modes. Anthracene, acridine, and carbocyanine-based chromophores have been examined for their DNA binding properties and photo-reactivities. Their planar aromatic structures make them ideal chromophores that can be used to probe DNA structural interactions and binding patterns. We have studied DNA binding and photocleavgage properties of a bisacridine chromophore joined by a 2,6-bis(aminomethyl)pyridine copper-binding linker (Chapter II), a series of 9-aminomethyl anthracene chromophores (Chapters III and IV), both under conditions of high and low ionic strength, as well as a series of pentamethine linked symmetrical carbocyanine dyes (Chapter V). In Chapter II we present data showing that high ionic strength efficiently increases copper(II)-dependent photocleavage of plasmid DNA by the bisacridine based chromophore (419 nm, pH 7.0). In Chapters III and IV, using an pyridine N-substituted 9-(aminomethyl)anthracene (Chapter III), a bis-9-(aminomethyl)anthracene, and its mono 9-(aminomethyl)anthracene analogue (Chapter IV), pUC19 plasmid DNA was photo-converted to highly diffuse DNA fragments (350 nm, pH 7.0) in the presence of 150 mM NaCl and 260 mM KCl. Spectroscopic analyses suggest that the combination of salts promotes a change in DNA helical structure that initiate a switch in anthracene binding mode from intercalation to an external or groove binding interactions. The alteration in DNA structure and binding mode leads to an increase in the anthracene-sensitized production of DNA damaging reactive oxygen species. Finally, in Chapter V, pUC19 plasmid DNA is converted to its nicked circular and linear forms following irradiation of a series of pentamethine linked symmetrical carbocyanines (red light, pH 7.0). The data suggest that the relative levels of photocleavage arise from the different substituents on the nitrogen alkyl side chain and the pentamethine linker.

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