ic6b00554_si_001.pdf (1.58 MB)
Photorelease and Cellular Delivery of Mitocurcumin from Its Cytotoxic Cobalt(III) Complex in Visible Light
journal contribution
posted on 2016-05-31, 18:54 authored by Aditya Garai, Ila Pant, Samya Banerjee, Bhabatosh Banik, Paturu Kondaiah, Akhil R. ChakravartyTernary cobalt(III) complexes of
curcumin (Hcur) and mitocurcumin [Hmitocur, a dicationic bis(triphenylphosphonium)
derivative of curcumin] having a tetradentate phenolate-based ligand
(H2L), namely, [Co(cur)(L)] (1) and [Co(mitocur)(L)]Cl2 (2), were prepared and structurally characterized,
and their photoinduced cytotoxicity was studied. The diamagnetic cobalt(III)
complexes show an irreversible Co(III)–Co(II) redox response
and a quasireversible curcuminoid-based reduction near −1.45
and −1.74 V SCE, respectively, in DMF/0.1 M [nBu4N](ClO4). The complexes exhibit a
curcumin/mitocurcumin-based absorption band near 420 nm. Complex 1 was structurally characterized by X-ray crystallography.
The structure contains the metal in a CoN2O4 distorted octahedral coordination arrangement with curcumin binding
to the metal in its enolic form. Binding to cobalt(III) increases
the hydrolytic stability of curcumin. Complex 2, having
a dicationic curcuminoid, shows significant cellular uptake and photoinduced
cytotoxicity compared to its curcumin analogue 1. The
dicationic cobalt(III) complex 2 has significantly better
cellular uptake and bioactivity than the neutral species 1. Complex 2 with mitochondrial localization releases
the mitocurcumin dye upon exposure to visible light (400–700
nm) in human breast cancer MCF-7 cells through photoreduction of cobalt(III)
to cobalt(II). Complex 2 displays a remarkable photodynamic
therapy (PDT) effect, giving an IC50 value of ∼3.9
μM in visible light (400–700 nm) in MCF-7 cells while
being much less toxic in the dark (>50 μM). The released
mitocurcumin acts as a phototoxin, generating intracellular reactive
oxygen species (ROSs). The overall process leads to light-controlled
delivery of a curcuminoid (mitocur) into the tumor cells while the
dye alone suffers from hydrolytic instability and poor bioavailability.