LE3 .A278 2009

2009

McFarland, Sherri

Acadia University

Bachelor of Science

Honours

Chemistry

Chemistry

This work investigated and characterized various ferrocene-conjugated ruthenium(II) complexes as potential agents for cancer treatment in photodynamic therapy (PDT). PDT is an emerging noninvasive treatment modality for cancerous tumors that facilitates the selective destruction of cancerous cells while maintaining the condition of the body’s healthy tissues. This method works through light-activation of a photosensitizing drug, which preferentially localizes within cancerous tissue, resulting in the tumor’s destruction. Current PDT agents are limited by (1) short-wavelength absorption, (2) reliance on molecular oxygen in the damage-inducing mechanism, (3) prolonged retention within various bodily tissues, (4) difficult reproducibility, and (5) poor selectivity toward target cells. With the hopes of addressing and overcoming these current limitations, three mixed-metal ferrocene-conjugated ruthenium(II) complexes have been investigated in order to assess their ability to induce DNA photocleavage. Furthermore, this study will broaden the knowledge of organometallics as synthetic photonucleases in PDT. All three complexes studied are cleave supercoiled (SC) pUC19 plasmid DNA with exposure to 420-nm light. UV-visible absorption spectral measurements indicate that the complexes show good DNA binding properties, while viscometric titration data suggests an intercalative mode of binding for the two complexes possessing planar 2-(pyrid-2’-yl)-1,8-naphthyridine ligands and a partial groove /partial intercalative mode of binding for the remaining mixed-metal complex. Mechanistic studies using various inhibitors reveal the involvement of singlet oxygen and hydroxyl radicals in the DNA photocleavage reactions for all three complexes. Deoxygenated photocleavage assays show that none of the studied complexes are x completely dependent on molecular oxygen to successfully achieve DNA photocleavage. Together the results of the mechanistic studies and the deoxygenated studies suggest that a number of DNA damaging pathways are induced by the iron-ruthenium(II) complexes included in this study. These results, and others, are detailed in this report.

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https://scholar.acadiau.ca/islandora/object/theses:586