Cobalt(III) Complexes for Light-Activated Delivery of Acetylacetonate-BODIPY, Cellular Imaging, and Photodynamic Therapy.

Cobalt(III) complexes [Co(TPA)(L)](ClO) (), [Co(4-COOH-TPA)(L)](ClO) (), [Co(TPA)(L)]Cl (), and [Co(4-COOH-TPA)(L)]Cl () having acetylacetonate-linked boron-dipyrromethene ligands (, acac-BODIPY; , acac-diiodo-BODIPY) were prepared and characterized, and their utility as bioimaging and phototherapeutic agents was evaluated (TPA, tris-(2-pyridylmethyl)amine; 4-COOH-TPA, 2-((bis-(2-pyridylmethyl)amino)methyl)isonicotinic acid). , , and complex were structurally characterized by X-ray crystallography. Complexes and on photoactivation or in a reducing environment (excess GSH, ascorbic acid, and 3-mercaptopropionic acid) released the acac-BODIPY ligand. They exhibited strong absorbance near 501 nm (ε ∼ (5.2-5.8) × 10 M cm) and emission bands near 513 nm (Φ ∼ 0.13, λ = 490 nm) in dimethyl sulfoxide (DMSO). Complexes and with absorption maxima at ∼536 and ∼538 nm (ε ∼ (1.2-1.8) × 10 M cm), respectively, afforded high singlet oxygen quantum yield (Φ ∼ 0.79) in DMSO. Complexes - showed Co(III)-Co(II) redox responses near -0.2 V versus saturated calomel electrode (SCE) in dimethylformamide (DMF)-0.1 M tetrabutylammonium perchlorate (TBAP). The photocleavage of pUC19 DNA by complex revealed the formation of both singlet oxygen and superoxide anion radicals as the reactive oxygen species (ROS). Confocal fluorescence microscopy showed the selective accumulation of complex in the endoplasmic reticulum (ER) in A-549 cells. Complex exhibited a high phototherapeutic index value (PI > 7000) in HeLa cancer cells (IC ∼ 0.007 μM in visible light of 400-700 nm, total dose ∼5 J cm). The ancillary ligands in the complexes demonstrated a structure-activity relationship and modulated the Co(III)-Co(II) redox potential, the complex solubility, acac-BODIPY ligand release kinetics, and phototherapeutic efficacy.