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

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.