Ferrocenyl-l-amino acid copper(ii) complexes showing remarkable photo-induced anticancer activity in visible light

Abstract

Ferrocene-conjugated copper(II) complexes [Cu(Fc-aa)(aip)](ClO4) (1–3) and [Cu(Fc-aa)(pyip)](ClO4) (4–6) of L-amino acid reduced Schiff bases (Fc-aa), 2-(9-anthryl)-1H-imidazo[4,5-f][1,10]phenanthroline (aip) and 2-(1-pyrenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (pyip), where Fc-aa is ferrocenylmethyl-L-tyrosine (Fc-Tyr in 1, 4), ferrocenylmethyl-L-tryptophan (Fc-Trp in 2, 5) and ferrocenylmethyl-L-methionine (Fc-Met in 3, 6), were prepared and characterized, and their photocytotoxicity was studied (Fc = ferrocenyl moiety). Phenyl analogues, viz. [Cu(Ph-Met)(aip)](ClO4) (7) and [Cu(Ph-Met)(pyip)](ClO4) (8), were prepared and used as control compounds. The bis-imidazophenanthroline copper(II) complexes, viz. [Cu(aip)2(NO3)](NO3) (9) and [Cu(pyip)2(NO3)](NO3) (10), were also prepared and used as controls. Complexes 1–6 having a redox inactive cooper(II) center showed the Fc+–Fc redox couple at ∼0.5 V vs. SCE in DMF–0.1 mol [Bun4N](ClO4). The copper(II)-based d–d band was observed near 600 nm in DMF–Tris-HCl buffer (1 : 1 v/v). The ferrocenyl complexes showed low dark toxicity, but remarkably high photocytotoxicity in human cervical HeLa and human breast adenocarcinoma MCF-7 cancer cells giving an excellent photo-dynamic effect while their phenyl analogues were inactive. The photo-exposure caused significant morphological changes in the cancer cells when compared to the non-irradiated ones. The photophysical processes were rationalized from the theoretical studies. Fluorescence microscopic images showed 3 and 6 localizing predominantly in the endoplasmic reticulum (ER) of the cancer cells, thus minimizing any undesirable effects involving nuclear DNA.