A copper(II) complex of 1,4,7-triazacyclononane featuring acetate pendant: an efficient DNA cleavage agent

A new water-soluble copper(II) complex, Cu(TACNA)Br?·?0.375H₂O (1) [TACNA?=?1,4,7-triazacyclononane-N-acetate], has been synthesized to serve as artificial nucleases. The X-ray crystal structure of 1 indicates that one bromide and an oxygen from acetate pendant coordinate to copper(II) in addition to the nitrogen atoms in the TACN macrocycle, resulting in a five-coordinate complex with square-pyramidal geometry. The interaction of 1 with calf thymus DNA (ct-DNA) has been investigated by UV absorption and fluorescence spectroscopies, and the mode of ct-DNA binding for 1 has been proposed. In the absence of external agents, supercoiled plasmid DNA cleavage by 1 was performed under aerobic condition; the influences on DNA cleavage of different complex concentrations and reaction times were also studied. The cleavage of plasmid DNA likely involves oxidative mechanism.     

Synthesis,DNA-binding,and antitumor activity of polypyridyl-ruthenium(II) complexes [Ru(L)2(DClPIP)] (L = bpy,phen; DClPIP = 2-(2,4-dichlorophenyl)-1H-imidazo[4,5-f][1, 10]phenanthroline)

Abstract

Two new ruthenium(II) complexes, [Ru(bpy)₂(DClPIP)](ClO₄)₂ (1) and [Ru(phen)₂(DClPIP)](ClO₄)₂ (2) (bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, and DClPIP = 2-(2,4-dichlorophenyl)-1H-imidazo[4,5-f][1, 10]phenanthroline), have been prepared in high yield by using microwave-assisted synthesis technology. The anticancer activity of the two ruthenium(II) complexes against A549, C6, CNE-1 and MDA-MB-231 cell lines has been evaluated by MTT assay and results showed that 2 exhibited higher antitumor activity than 1 toward all the selected tumor cell lines. Besides, A549 cell line was sensitive to both ruthenium(II) complexes, especially to 2 (IC₅₀ = 8.01?±?0.36?μM). Meanwhile, 2 showed low toxicity against MCF-10A human normal cells. Furthermore, the DNA-binding properties of the two new ruthenium(II) complexes with CT-DNA have been investigated by electronic absorption titration, luminescence spectra, circular dichroism spectra and viscosity measurements. The results suggested that 1 and 2 were able to interact with CT-DNA via intercalative mode with a strong binding affinity in the order 2?>?1. All of these results suggested that anticancer activity of both ruthenium(II) complexes could be closely related to their interaction with DNA.     

A V-shaped ligand bis(N-methylbenzimidazol-2-ylmethyl) benzylamine with its cobalt(II) complex: synthesis,crystal structure,DNA-binding properties,and antioxidant activity

A V-shaped ligand bis(N-methylbenzimidazol-2-ylmethyl)benzylamine (bmbb) and its cobalt complex, [Co(bmbb)₂](pic)₂ (pic?=?picrate), have been synthesized and characterized by physico-chemical and spectroscopic methods. Single-crystal X-ray revealed that the coordination sphere around Co(II) is distorted octahedral with an N₆ ligand set from two tridentate bmbb. The DNA-binding properties of bmbb and the Co(II) complex were investigated by spectrophotometric and viscosity measurements. The results suggest that bmbb and Co(II) complex both bind to DNA via intercalation, and the Co(II) complex binds to DNA more strongly than bmbb. The Co(II) complex also exhibited potential antioxidant properties in vitro studies.     

Synthesis,characterization, DNA-binding and DNA-photocleavage studies of [Ru(bpy)2(pmip)] and [Ru(phen)2(pmip)] (pmip = 2-(2′-pyrimidyl)imidazo[4,5-f][1,10]phenanthroline

Two new Ru(II) complexes, [Ru(bpy)₂(pmip)]²⁺ (1) and [Ru(phen)₂(pmip)]²⁺ (2), have been synthesized and characterized by elemental analysis, ESI-MS and ¹H NMR spectra. Their DNA-binding properties were studied by means of UV–VIS, emission and CD spectra, thermal denaturation and viscosity measurements as well as their DNA-photocleavage properties. The experimental results show that both 1 and 2 can bind to DNA in an intercalative mode; the DNA-binding affinity of 2 is greater than that of 1, which suggests that the ancillary ligands have a significant effect on the spectroscopic properties and DNA-binding behavior of the Ru(II) complexes. Under irradiation with UV light, the Ru(II) complexes show excellent efficiency of cleaving DNA. This research may provide valuable insight into the interactions of metal complexes with DNA, knowledge that is an excellent backdrop for the rational design of promising drugs.     

Crystal structures,DNA-binding ability and influence on cellular viability of gold(I) complexes of thiosemicarbazones

The present study reports the synthesis and crystal structure of four novel gold(I) complexes with di-2-pyridyl ketone N(4)-ethylthiosemicarbazone (L¹) and 2-acetylfuran-4-methyl-3-thiosemicarbazone (L²). All the gold(I) complexes were observed with monodentate thiosemicarbazones and exhibited gold(I) ions with linear geometries, bound to a sulfur atom of the ligand and a halogen ion (Br^? or Cl^?). The crystal structures of gold complexes with Br^? and thiosemicarbazone are the first examples reported. Interestingly, 2[AuBr(HL¹)]2Br was observed to have a Au?Au length of 3.155(8) Å, and this distance suggests an unusual Au?Au interaction in the solid state. The ability of the thiosemicarbazones and the corresponding gold(I) complexes to bind to DNA was studied by UV-vis and emission spectroscopy. The effect on cell viability of the compounds was evaluated against human breast cancer cell lines. The results show that the gold(I) complexes exhibit more potent inhibition of tumor growth than the free ligands.     

Solvent dependent selective alkylation of a bis(sulfonamide) for the synthesis of a DNA-binding chiral polyamine

A new optically active linear polyamine has been efficiently prepared and its DNA binding abilities studied by UV melting experiments. The key step for this synthesis was the selective monoalkylation of the corresponding bis(sulfonamide). Thus, it is possible to obtain mono or dialkylated compounds by simply changing the reaction conditions. These results are explained in terms of conformational preferences and solvophobic effects.     

Syntheses,crystal structures,and DNA-binding properties of two nickel(II) complexes with 1,3-bis(benzimidazol-2-yl)-2-oxapropane derivatives

[Ni(obb)(DMF)₂(H₂O)]·(Pic)₂·0.5DMF (1) and [Ni(Etobb)₂]·(Pic)₂·2DMF (2) (obb = 1,3-bis(benzimidazol-2-yl)-2-oxapropane, Etobb = 1,3-bis(1-ethylbenzimidazol-2-yl)-2-oxapropane, Pic = picrate) have been synthesized and characterized by physicochemical and spectroscopic methods. The structures of both complexes have been determined by X-ray single-crystal diffraction. The coordination geometries of 1 and 2 can be described as distorted octahedra. The interaction of the nickel(II) complexes with calf thymus DNA was investigated by electronic absorption, fluorescence spectroscopy, and viscosity measurements. The experimental results suggest that 1 and 2 bind to DNA in an intercalation mode, and their binding affinity for DNA follows the order 1 > 2. DNA-binding behaviors can be attributed to the large coplanar aromatic rings in the V-shaped ligand and steric hindrance.     

DNA-Binding Capabilities and Anticancer Activities of Ruthenium(II) Cymene Complexes with (Poly)cyclic Aromatic Diamine Ligands

Ruthenium(II) arene complexes of the general formula [RuCl(η⁶-p-cymene)(diamine)]PF₆ (diamine = 1,2-diaminobenzene (1), 2,3-diaminonaphthalene (2), 9,10-diaminophenanthrene (3), 2,3-diaminophenazine (4), and 1,2-diaminoanthraquinone (5) were synthesized. Chloro/aqua exchange was evaluated experimentally for complexes 1 and 2. The exchange process was investigated theoretically for all complexes, revealing relatively fast exchange with no significant influence from the polycyclic aromatic diamines. The calf thymus DNA (CT-DNA) binding of the complexes increased dramatically upon extending the aromatic component of the diamines, as evaluated by changes in absorption spectra upon titration with different concentrations of CT-DNA. An intercalation binding mode was established for the complexes using the increase in the relative viscosity of the CT-DNA following addition of complexes 1 and 2. Theoretical studies showed strong preference for replacement of water by guanine for all the complexes, and relatively strong Ru–N_guanine bonds. The plane of the aromatic systems can assume angles that support non-classical interactions with the DNA and covalent binding, leading to higher binding affinities. The ruthenium arenes illustrated in this study have promising anticancer activities, with the half maximal inhibitory concentration (IC₅₀) values comparable to or better than cisplatin against three cell lines.     

Five new cobalt(II) complexes based on indazole derivatives: synthesis,DNA binding and molecular docking study

Five cobalt(II) complexes based on 1H-indazole-3-carboxylic acid (H₂L), [Co(phen)(HL)₂]·2H₂O (1), [Co(5,5′-dimethyl-2,2′-bipy)(HL)₂] (2), [Co(2,2′-bipy)₂(HL)₂]·5H₂O (3), [Co₂(2,9-dimethyl-1,10-phen)₂(L)₂] (4) and [Co₂(6,6′-dimethyl-2,2′-bipy)₂(L)₂]·H₂O (5) (2,2'-bipy = 2,2′-bipyridine, phen = 1,10-phenanthroline), have been synthesized and structurally characterized by elemental analyses, IR and UV-vis spectroscopies and single-crystal X-ray crystallography. The results indicate that 1–3 possess mononuclear Co(II) structures, while 4 and 5 exhibit binuclear structure. 1D water tape which is linked by the multiple hydrogen bonds was embedded in the 3D motif of complex 3. Complexes 4 and 5 show two orthogonal planes of motif that was constituted by phen/2,2′-bipy and indazole acid, respectively. The intermolecular interactions including hydrogen bonding and π-π stacking interactions are stabilizing these complexes. The interactions of the synthesized complexes with calf-thymus DNA (CT-DNA) have been investigated by UV-vis absorption titration, ethidium bromide displacement assay and viscosity measurements. The results reveal that the complexes could interact with CT-DNA via a groove binding mode. Their behavior rationalization was further theoretically studied by molecular docking.