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.