Ferrocene-Conjugated Copper(II) Complexes of l-Methionine and Phenanthroline Bases: Synthesis, Structure, and Photocytotoxic Activity

Abstract

Ferrocene-conjugated reduced Schiff base (Fc-metH) copper(II) complexes of l-methionine and phenanthroline bases, namely, [Cu(Fc-met)(B)](NO3), where B is 1,10-phenanthroline (phen in 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq in 2), dipyrido[3,2-a:2′,3′-c]phenazine (dppz in 3), and 2-(naphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (nip in 4), were prepared and characterized and their photocytotoxicity studied (Fc = ferrocenyl moiety). Complexes [Cu(Ph-met)(B)](NO3) of the reduced Schiff base from benzaldehyde and l-methionine (Ph-metH) and B (phen in 5, dppz in 6) were prepared and used as control species. Complexes 1 and 5 were structurally characterized by X-ray crystallography. Complex 1 as a discrete monomer has a CuN3OS core with the thiomethyl group as the axial ligand. Complex 5 has a polymeric structure with a CuN3O2 core in the solid state. Complexes 5 and 6 are formulated as [Cu(Ph-met)(B)(H2O)](NO3) in an aqueous phase based on the mass spectral data. Complexes 1–4 showed the Cu(II)–Cu(I) and Fc+–Fc redox couples at ∼0.0 and ∼0.5 V vs SCE, respectively, in DMF–0.1 M [Bun4N](ClO4). A Cu(II)-based weak d–d band near 600 nm and a relatively strong ferrocenyl band at ∼450 nm were observed in DMF–Tris-HCl buffer (1:4 v/v). The complexes bind to calf thymus DNA, exhibit moderate chemical nuclease activity forming •OH radical species, and are efficient photocleavers of pUC19 DNA in visible light of 454, 568, and 647 nm, forming •OH radical as the reactive oxygen species. They are cytotoxic in HeLa (human cervical cancer) and MCF-7 (human breast cancer) cells, showing an enhancement of cytotoxicity upon visible light irradiation. Significant change in the nuclear morphology of the HeLa cells was observed with 3 in visible light compared to the nonirradiated sample. Confocal imaging using 4 showed its nuclear localization within the HeLa cells.