title: Cobalt(II) complexes of terpyridine bases as photochemotherapeutic agents showing cellular uptake and photocytotoxicity in visible light.
abstract: Cobalt(II) complexes of terpyridine bases [Co(L)₂](ClO₄)₂ (1-3), where L is 4'-phenyl-2,2':6',2''-terpyridine (ph-tpy in 1), 4'-(9-anthracenyl)-2,2':6',2''-terpyridine (an-tpy in 2) and 4'-(1- pyrenyl)-2,2':6',2''-terpyridine (py-tpy in 3), are prepared and their photo-induced DNA and protein cleavage activity and photocytotoxic property in HeLa cells studied. The 1 : 2 electrolytic and three-electron paramagnetic complexes show a visible band near 550 nm in DMF-Tris-HCl buffer. The complexes 1-3 show emission spectral bands at 355, 421 and 454 nm, respectively, when excited at 287, 368 and 335 nm. The quantum yield values for 1-3 in DMF-H₂O (2 : 1 v/v) are 0.025, 0.060 and 0.28, respectively. The complexes are redox active in DMF-0.1 M TBAP. The Co(III)-Co(II) and Co(II)-Co(I) couples appear as quasi-reversible cyclic voltammetric responses near 0.2 and -0.7 V vs. SCE, respectively. Complexes 2 and 3 are avid binders to calf thymus DNA giving K(b) value of ∼10⁶ M⁻¹. The complexes show chemical nuclease activity. Complexes 2 and 3 exhibit oxidative cleavage of pUC19 DNA in UV-A and visible light. The DNA photocleavage reaction of 3 at 365 nm shows formation of singlet oxygen and hydroxyl radical species, while only hydroxyl radical formation is evidenced in visible light. Complexes 2 and 3 show non-specific photo-induced bovine serum albumin protein cleavage activity at 365 nm. The an-tpy and py-tpy complexes exhibit significant photocytotoxicity in HeLa cervical cancer cells on exposure to visible light giving IC₅₀ values of 24.2 and 7.6 μM, respectively. Live cell imaging study shows accumulation of the complexes in the cytosol of HeLa cancer cells.
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, 560012, India.
authors.forename: Sovan
authors.initials: S
authors.lastname: Roy
authors.forename: Subhendu
authors.initials: S
authors.lastname: Roy
authors.forename: Sounik
authors.initials: S
authors.lastname: Saha
authors.forename: Ritankar
authors.initials: R
authors.lastname: Majumdar
authors.forename: Rajan R
authors.initials: RR
authors.lastname: Dighe
authors.forename: Eluvathingal D
authors.initials: ED
authors.lastname: Jemmis
authors.forename: Akhil R
authors.initials: AR
authors.lastname: Chakravarty
mesh_terms: D000818:Animals; D002417:Cattle; D003035:Cobalt / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D053837:DNA Cleavage; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D008027:Light; D008856:Microscopy, Fluorescence; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D010084:Oxidation-Reduction; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011725:Pyridines / Q000737:chemistry*; D011789:Quantum Theory; D012710:Serum Albumin, Bovine / Q000378:metabolism
chemical_list: D056831:Coordination Complexes; D008024:Ligands; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011725:Pyridines; D012710:Serum Albumin, Bovine; D003035:Cobalt; C023666:pyridine