Ferrocene-conjugated L-tryptophan copper(II) complexes of phenanthroline bases showing DNA photocleavage activity and cytotoxicity.

Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India.
Inorganic Chemistry (Impact Factor: 4.59). 07/2011; 50(17):8452-64. DOI: 10.1021/ic201028e
Source: PubMed

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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Two novel copper(II) bromide complexes with pyridine containing Schiff base ligands, and where pmed = N'-((pyridin-2-yl)methylene)ethane-1,2-diamine (pmed) and dpmed = N,N-diethyl-N'-((pyridin-2-yl)methylene)ethane-1,2-diamine (dpmed) were synthesized and characterized using X-ray single crystal structure analysis, optical and magnetic susceptibility measurements. Crystal structural analysis of showed that the copper(II) ion has a distorted square-pyramidal geometry with the trigonality index of and two intermolecular hydrogen bonds, which result in the formation of two dimensional networks in the ab plane. On the other hand, displayed a near square-pyramidal geometry with the value of . In both compounds, the NNN Schiff base and one Br atom occupy the basal plane, whereas the fifth apical position is occupied by the other Br atom at a greater Cu-Br apical distance. The reported complexes show > > 2.0023 with a ground state and a penta-coordinated square pyramidal geometry. Variable temperature magnetic susceptibility measurements showed that the developed copper(II) complexes follow the Curie-Weiss law, that is there are no magnetic interactions between the copper(II) ions since the Cu--Cu distance is too far for magnetic contact.
    Bulletin- Korean Chemical Society 01/2013; 34(12). · 0.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Iron(III) complexes [Fe(L)(L′)(NO3)]—in which L is phenyl-N,N-bis[(pyridin-2-yl)methyl]methanamine (1), (anthracen-9-yl)-N,N-bis[(pyridin-2-yl)methyl]methanamine (2), (pyreny-1-yl)-N,N-bis[(pyridin-2-yl)methyl]methanamine (3–5), and L′ is catecholate (1–3), 4-tert-butyl catecholate (4), and 4-(2-aminoethyl)-benzene-1,2-diolate (5)—were synthesized and their photocytotoxic properties examined. The five electron-paramagnetic complexes displayed a FeIII/FeII redox couple near −0.4 V versus a saturated calomel electrode (SCE) in DMF/0.1 m tetrabutylammonium perchlorate (TBAP). They showed unprecedented photocytotoxicity in red light (600–720 nm) to give IC50≈15 μM in various cell lines by means of apoptosis to generate reactive oxygen species. They were ingested in the nucleus of HeLa and HaCaT cells in 4 h, thereby interacting favorably with calf thymus (ct)-DNA and photocleaving pUC19 DNA in red light of 785 nm to form hydroxyl radicals.
    Chemistry - An Asian Journal 07/2014; · 4.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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-Ltyrosine (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 [Bun 4N](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.
    Dalton Transactions 01/2014; · 4.10 Impact Factor