PAH-appended phenanthroline ligands for use in photodynamic therapy
LE3 .A278 2009
Bachelor of Science
Octahedral ruthenium(II) complexes of the form [Ru(bpy)2L]2+, where bpy = 2,2‟-bipyridine and L = PAH-appended 1,10-phenanthroline, were explored for use in photodynamic therapy (PDT). PDT is a chemotherapeutic technique that employs a photosensitizing drug which tends to accumulate in malignant tissue and upon selective irradiation destroys cancerous cells. The compounds 1-4 were designed to overcome the limitations of current PDT agents, including (i) short wavelength absorption, (ii) reliance on dioxygen to function, (iii) retention by target tissue, (iv) low reproducibility, and (v) prolonged side effects following treatment. This investigation extended existing reports that polypyridyl-ruthenium systems can both bind to DNA and cause photoinduced strand cleavage in supercoiled plasmids. Interactions between the complexes and DNA were monitored using agarose gel electrophoresis and a series of binding studies. Key results emphasized the mono-substituted ethynylpyrene ligands as the most efficient and potent DNA photocleavers, having EC50 values in the nanomolar region and evidence for double-strand DNA breaks. These compounds were also found to have the most pronounced changes in UV-VIS spectral measurements, DNA melting temperatures, and relative viscosity, concluding their intercalative mode of DNA binding. The disubstituted-ethynylpyrene and mono-substituted perylene complexes disclosed moderate shifts in UV-VIS spectral studies, DNA melt curves, and viscosity measurements owing to their minor groove binding and partial intercalating propensities. All compounds showed slight oxygen dependence once degassed with argon except the 5-substituted ethynylpyrene phenanthroline complex which was equally as effective under the anaerobic conditions.
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