Ferrocene-Conjugated l-Tryptophan Copper(II) Complexes of Phenanthroline Bases Showing DNA Photocleavage Activity and Cytotoxicity

Abstract

Ferrocene-conjugated L-tryptophan (L-Trp) reduced Schiff base (Fc-TrpH) copper(II) complexes [Cu(Fc-Trp)(L)](ClO(4)) of phenanthroline bases (L), viz. 2,2'-bipyridine (bpy in 1), 1,10-phenanthroline (phen in 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 3), and dipyrido[3,2-a:2',3'-c]phenazine (dppz in 4), were prepared and characterized and their photocytotoxicity studied. Cationic reduced Schiff base (Ph-TrpH) complexes [Cu(Ph-Trp)(L)(H(2)O)](ClO(4)) (L = phen in 5; dppz in 6) having the ferrocenyl moiety replaced by a phenyl group and the Zn(II) analogue (7) of complex 4 were prepared and used as control species. The crystal structures of 1 and 5 with respective square-planar CuN(3)O and square-pyramidal CuN(3)O(2) coordination geometry show significantly different core structures. Complexes 1-4 exhibit a Cu(II)-Cu(I) redox couple near -0.1 V and the Fc(+)-Fc couple at ~0.5 V vs SCE in DMF-0.1 M [Bu(n)(4)N](ClO(4)) (Fc = ferrocenyl moiety). The complexes display a copper(II)-based d-d band near 600 nm and a Fc-centered band at ~450 nm in DMF-Tris-HCl buffer. The complexes are efficient binders to calf thymus DNA. They are synthetic chemical nucleases in the presence of thiol or H(2)O(2), forming hydroxyl radicals. The photoactive complexes are cleavers of pUC19 DNA in visible light, forming hydroxyl radicals. Complexes 2-6 show photocytotoxicity in HeLa cancer cells, giving IC(50) values of 4.7, 10.2, 1.3, 4.8, and 4.3 μM, respectively, in visible light with the appearance of apoptotic bodies. The complexes also show photocytotoxicity in MCF-7 cancer cells. Nuclear chromatin cleavage has been observed with acridine orange/ethidium bromide (AO/EB) dual staining with complex 4 in visible light. The complexes induce caspase-independent apoptosis in the HeLa cells.

Methyl substituent effect on one‐dimensional copper(II) coordination polymers containing biologically active ligands: Synthesis, characterization, DNA interactions and cytotoxicities

“…The calculated K b of 1 – 3 to CT‐DNA were found to be of lower magnitude than that of the classical intercalator EB ( K b = 1.23 × 10 5 M −1 , log K b = 5.09) . However, the K b values for these complexes are comparable to those observed for other copper(II) complexes (Table ).…”

Mechanistic insights into a novel chromone-appended Cu(ii) anticancer drug entity: in vitro binding profile with DNA/RNA substrates and cytotoxic activity against MCF-7 and HepG2 cancer cells

“…The perturbations in the CD signals of B-DNA have been attributed to the corresponding alterations in positive band at 275 nm (due to base stacking) and a negative band at 246 nm (due to right handed helicity), which are quite subtle to the modes of DNA interaction. 41 However, only nominal effects on the DNA viscosity are observed if electrostatic or groove binding occurs in the binding process. The CD spectrum of 1-DNA system [Complex]/[DNA = 1] exhibited a decrease in intensity of the both negative and positive bands accompanied by an ∼5 nm red shift; nevertheless, a marked decrease was observed in the ellipticity band signature (Fig.…”

Oxovanadium(iv) catecholates of terpyridine bases for cellular imaging and photocytotoxicity in red light

“…[19][20][21][22] Redox active copper(II) complexes are generally not suitable for PDT due to their high cellular dark toxicity arising from the reduction of copper(II) to copper(I) by thiols and the reduced species generates cytotoxic reactive oxygen species (ROS) in the presence of molecular oxygen. 23,24 The oxovanadium(IV) complexes generally show d-d bands with very low molar extinction coefficient values making them ineffective as near-IR light photosensitizers. 21,22 To overcome these predicaments, we have designed new oxovanadium(IV) complexes of catecholate ligands showing ligand-to-metal charge transfer (LMCT) band(s) near 500 nm along with the metal-centred band near 750 nm.…”