Cobalt(II) complexes of terpyridine bases as photochemotherapeutic agents showing cellular uptake and photocytotoxicity in visible light

摘要

Cobalt(ii) complexes of terpyridine bases [Co(L)2](ClO 4)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-H_2O (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 Kb value of ～10~6 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 IC_(50) 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.