LE3 .A278 2011

2011

McFarland, Sherri

Acadia University

Bachelor of Science

Honours

Chemistry

Chemistry

Ruthenium complexes of the type [Ru(LL)2(LL‟)]2+ (LL = 2,2‟-bipyridine, 1,10-phenanthroline; LL‟ = substituted imidazo- or oxazolo[4,5-f][1,10]phenanthroline) were synthesized, characterized and tested for their ability to bind to, and photocleave, DNA. Complexes were designed in hopes that such abilities would translate to photocytotoxicity in vitro, and therefore show potential as new photosensitizers for photodynamic therapy (PDT), a form of chemotherapy involving the use of a photoactivated drug to inflict selective tissue damage following directed irradiation. Polypyridal Ru(II) complexes are reported in literature to bind to, and cause photo-induced cleavage of, DNA, and these results are extended to new complexes in this study. Complex 1a demonstrated very strong DNA binding ability in UV-Vis DNA titration experiments, and both 1a and 1b showed significant DNA photocleaving ability in experiments monitored using agarose gel electrophoresis. Photocytotoxicity of the synthesized ruthenium complexes was evaluated through cell culture assays employing human leukemia (HL-60) cells to study how DNA binding and photocleaving behavior would translate within the cell. All complexes exhibited some toxicity, however several showed significant amounts of dark toxicity and, therefore, do not represent promising molecules for PDT applications. Complexes 1a and 1b, however, induced little dark toxicity but caused photocytotoxicity in nearly all cells at 100 μM, killing 79 % and 67 % more cells, respectively, than in dark controls. This suggests that the damaging behavior of these molecules in photocleavage assays can also occur within HL60 cells. These results point to Ru(II) coordination complexes containing 2-(2‟,2‟‟-bithiophene)imidazo[4,5-f][1,10]phenanthroline ligands (1a, 1b) as promising candidates in the field of inorganic photodynamic therapy, and warrant future investigations to confirm their potentia

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https://scholar.acadiau.ca/islandora/object/theses:1174