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 (L 1 , acac-BODIPY; L 2 , 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). HL 1 , HL 2 , 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.

Luminescent and Photofunctional Transition Metal Complexes: From Molecular Design to Diagnostic and Therapeutic Applications

“…However, it is challenging to develop luminescent complexes with first-row transition metals due to the efficient nonradiative deactivation via the low-lying MC excited states . Thus, these complexes typically require a fluorescent ligand for tracking their intracellular localization. − Nevertheless, recent findings have demonstrated that with a rationally designed ligand framework, these complexes can be made luminescent with long excited-state lifetimes in solution at room temperature; , representative examples include those of vanadium, chromium, − manganese, iron, − cobalt, , nickel, and copper. − Luminescent complexes of other earth-abundant metals such as zirconium, − molybdenum, − and tungsten − have also been developed for applications in OLEDs and photocatalysis. Conversely, the efficient nonradiative decays of first-row transition metal complexes can be harnessed to develop PTAs for photoacoustic imaging and PTT when the complexes display intense NIR absorption. − Thus, it is foreseeable that a strategic design of ligand systems will lead to the development of photoactive earth-abundant transition metal complexes for biosensing, bioimaging, and phototherapeutic applications.…”

Polypyridyl CoII‐Curcumin Complexes as Photoactivated Anticancer and Antibacterial Agents

“…Recently, many Co III complexes have been reported to show visible light‐catalyzed toxicity to cancer cells through oxidative stress generation [19,22b,37] . The intense visible light band of 3 and 4 at around 425 nm indicated that these complexes may induce cancer cell death on white light excitation.…”

“…[8][9][10][11][12][13][14][15] In general metal-based photo-sensitizers contain photoresponsive ligand(s) that lead to light absorption properties in the visible region. [7][8][9][10][11][12][13][14][15][18][19][20] Over the past few years, curcumin, a bright yellow polyphenolic constituent of turmeric, has been used as an efficient photoresponsive ligand to design metal-based photosensitizers. [21][22][23][24][25][26][27] Besides its photosensitizing capabilities under visible light, it promotes apoptosis in cancerous cells by changing NF-kB functioning.…”

“…Therefore, the development of new metal‐based photosensitizers for photodynamic therapy has gained great interest [8–15] . In general metal‐based photosensitizers contain photoresponsive ligand(s) that lead to light absorption properties in the visible region [7–15,18–20] . Over the past few years, curcumin, a bright yellow polyphenolic constituent of turmeric, has been used as an efficient photoresponsive ligand to design metal‐based photosensitizers [21–27] .…”

“…Co is one of the bio‐essential and highly biocompatible elements [22b] . Recently, attention is paid to producing Co‐based photosensitizers for PDT applications [19,22b,35–39] . For this purpose, researchers have mostly explored Co in the +3 oxidation state [19,22b,35–40] .…”