Discovering the Potential of Photoluminescent Ruthenium(II) Complexes as Photodynamic Therapy Agents
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Anthracene was attached to light activated, ruthenium-based DNA disruptors to probe their distribution in cancer cells. The objective of this research is to understand the photophysical properties (Chapter 2), photoreactivity toward DNA and proteins (Chapter 3), and localization within cancer cells (Chapter 4) of ruthenium complexes that demonstrate promise as photodynamic therapy (PDT) agents. [(AnthbpyMe)(bpy)Ru(dpp)]2+ (1) and [(AnthbpyMe)2Ru(dpp)]2+ (2) absorb visible light with metal-to-ligand charge transfer (MLCT) transitions at 459 nm (16,000 M-1cm-1) and 461 nm (21,000 M-1cm-1), respectively. These species exhibit 3MLCT emissions at �[BULLET]em = 661 nm and �[BULLET]em = 663 nm for 1 and 2, respectively, while the anthracene show emissions at 450 �" 560 nm. The anthracene unit(s) quench the 3MLCT to give quantum yields (lifetime) of �[BULLET]em = 0.0059 [398(1) ns] and �[BULLET]em = 0.0011 [414(1) ns] for 1 and 2, respectively. Voltammetry shows an irreversible anthracene oxidation at 1.23 �" 1.28 V, RuIII/II oxidation at 1.53 �" 1.55 V, and quasi-reversible reduction couples attributed to dpp0/-1 at 0.98 V. DNA gel shift assays demonstrate that complexes 1 and 2 modify DNA in the presence and absence of 3O2 upon light activation to convert supercoiled DNA to a mixture of open circular (OC) DNA and a species that exhibit sa distinctly different migration rate than either OC and linear DNA. Binding constants, Kb, for complexes 1 and 2, toward DNA are 3.50 �-- 105(3.50 �-- 104 ) and 4.50 �-- 103(4.50 �-- 102) respectively. SDS-PAGE assays show that the complexes 1 and 2 modify bovine serum albumin (BSA) through an 3O2-dependent mechanism upon light activation. The localization and PDT potency of the anthracene-Ru-dpp complexes are tested against F98 cells, which are rat glioma cells that simulate the infiltrative patterns of growth in cancer. Confocal microscopy demonstrates that complexes 1 and 2 internalize and localize primarily along the cell membrane and associate with dot-like vesicles within the cytoplasm. Complexes 1 and 2 show IC50 values of 107 μM and 85 μM, respectively, after 15 min of drug exposure and 1 h of PDT-treatment (�[BULLET]PDT = 455 nm).
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