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

Abstract

Cobalt(III) complexes [Co(TPA)(L1)](ClO4)2 (1), [Co(4-COOH-TPA)(L1)](ClO4)2 (2), [Co(TPA)(L2)]Cl2 (3), and [Co(4-COOH-TPA)(L2)]Cl2 (4) having acetylacetonate-linked boron-dipyrromethene ligands (L1, acac-BODIPY; L2, 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). HL1, HL2, and complex 1 were structurally characterized by X-ray crystallography. Complexes 1 and 2 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) × 104 M-1 cm-1) and emission bands near 513 nm (ΦF ∼ 0.13, λex = 490 nm) in dimethyl sulfoxide (DMSO). Complexes 3 and 4 with absorption maxima at ∼536 and ∼538 nm (ε ∼ (1.2-1.8) × 104 M-1 cm-1), respectively, afforded high singlet oxygen quantum yield (ΦΔ ∼ 0.79) in DMSO. Complexes 1-4 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 4 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 1 in the endoplasmic reticulum (ER) in A-549 cells. Complex 4 exhibited a high phototherapeutic index value (PI > 7000) in HeLa cancer cells (IC50 ∼ 0.007 μM in visible light of 400-700 nm, total dose ∼5 J cm-2). 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.