title: Photorelease and Cellular Delivery of Mitocurcumin from Its Cytotoxic Cobalt(III) Complex in Visible Light.
abstract: Ternary 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 [(n)Bu4N](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.
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Aditya
authors.initials: A
authors.lastname: Garai
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Ila
authors.initials: I
authors.lastname: Pant
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Samya
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Bhabatosh
authors.initials: B
authors.lastname: Banik
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Paturu
authors.initials: P
authors.lastname: Kondaiah
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Akhil R
authors.initials: AR
authors.lastname: Chakravarty
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D003035:Cobalt / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008027:Light; D061986:MCF-7 Cells; D010778:Photochemotherapy
chemical_list: D056831:Coordination Complexes; D003035:Cobalt; D003474:Curcumin