Terpyridine Copper Research Articles

Antitumor activity of synthetic three copper(II) complexes with terpyridine ligands

Three new synthetic terpyridine copper(II) complexes were characterized. The copper(II) complexes induced apoptosis of three cancer cell lines and arrested T-24 cell cycle in G1 phase. The complexes were accumulated in mitochondria of T-24 cells and caused significant reduction of the mitochondrial membrane potential. The complexes increased both intracellular ROS and Ca2+ levels and activated the caspase-3/9 expression. The apoptosis was further confirmed by Western Blotting analysis. Bcl-2 was down-regulated and Bax was upregulated after treatment with complexes 1–3. The in vivo studies showed that complexes 1–3 obviously inhibited the growth of tumor without significant toxicity to other organs.

Terpyridine copper(II) complexes as potential anticancer agents by inhibiting cell proliferation, blocking the cell cycle and inducing apoptosis in BEL-7402 cells.

Four mononuclear terpyridine complexes [Cu(H-La)Cl2]·CH3OH (1), [Cu(H-La)Cl]ClO4 (2), [Cu(H-Lb)Cl2]·CH3OH (3), and [Cu(H-Lb)(CH3OH)(DMSO)](ClO4)2 (4) were prepared and fully characterized. Complexes 1-4 exhibited higher cytotoxic activity against several tested cancer cell lines especially BEL-7402 cells compared to cisplatin, and they showed low toxicity towards normal human liver cells. ICP-MS detection indicated that the copper complexes were accumulated in mitochondria. Mechanistic studies demonstrated that the copper complexes induced G0/G1 arrest and altered the expression of the related proteins of the cell cycle. All copper complexes reduced the mitochondrial membrane potential while increasing the intracellular ROS levels and the release of Ca2+. They also up-regulated Bax and down-regulated Bcl-2 expression levels, caused cytochrome c release and the activation of the caspase cascade, and induced mitochondrion-mediated apoptosis. Animal studies demonstrated that complex 1 suppressed tumor growth in a mouse xenograft model bearing BEL-7402 tumor cells.

Electrocatalytic Determination of Cysteine Using a Carbon Ionic Liquid Electrode Modified with Terpyridine Copper(II) Complex

ABSTRACTThe oxidation of L-cysteine was studied on a carbon ionic liquid electrode modified with terpyridine copper(II) complex (4′-phenyl-2,2′:6’,2″-terpyridine copper(II)). Cysteine provided an oxidation peak at the relatively low overpotential value of approximately 40 mV at the modified electrode. The oxidation current significantly increased, suggesting high electrocatalytic activity of the terpyridine copper(II) complex toward cysteine. The oxidation current was proportional to cysteine concentration from 0.1 to 40 µM with a limit of detection 0.01 µM. The response of the modified electrode to cysteine was studied in the presence of ascorbic acid, tyrosine, glucose, glycine, uric acid, and dopamine. No interferences were observed. The method was employed for the determination of cysteine in serum.

Remote steric effects of C2-symmetric planar-chiral terpyridine ligands on copper-catalyzed asymmetric cyclopropanation reactions

A series of enantioselective cyclopropanation reactions of substituted alkenes with diazoacetates was investigated in the presence of Cu(OTf)2 with C2-symmetric planar-chiral bridged 2,2′:6′,2″-terpyridines. Planar-chiral terpyridine–copper complexes exhibited moderate diastereomeric excesses with good enantioselectivities of cis-cyclopropane products in catalytic asymmetric cyclopropanation reactions of various styrene derivatives with ethyl diazoacetate. A remote steric effect was found to enhance enantioselectivity for the cyclopropanation induced by a sterically demanding substituent beyond the ansa-bridge of pyridinophane ligands on the other side of the reaction site as a relay of steric influences through flexible cyclophane bridges.

New ternary bipyridine–terpyridine copper(ii) complexes as self-activating chemical nucleases

New copper complexes with an impressive DNA cleaving ability in the absence of any exogenous oxidants or reductants.

Facile synthesis of 5-substituted-1H-tetrazoles and 1-substituted-1H-tetrazoles catalyzed by recyclable 4′-phenyl-2,2′:6′,2″-terpyridine copper(II) complex immobilized onto activated multi-walled carbon nanotubes

5-Substituted-1H-tetrazoles can conveniently be synthesized from the corresponding nitriles by reaction with NaN3 using the efficient and recyclable heterogeneous catalyst prepared by immobilization of copper(II) complex of 4′-phenyl-2,2′:6′,2″-terpyridine on activated multi-walled carbon nanotubes [AMWCNTs-O–Cu(II)–PhTPY]. Excellent results were obtained in each case affording the corresponding tetrazole adducts in good to excellent yields. In general, aromatic nitriles with electron-donating group could be accomplished as well as that with electron-withdrawing groups. By leaving out nitrile from the reaction and adding CH(OEt)3 and amines bearing various substituents, 1-substituted-1H-tetrazoles formed in water in high yields. The reported protocols have the advantages of rapid assembly of a host of heterocyclic systems in high yields with the added advantage of recycling and reuse of the catalyst.

Synthesis of Vasorelaxaing 1,4‐Disubstituted 1,2,3‐Triazoles Catalyzed by a 4′‐Phenyl‐2,2′:6′,2′′‐Terpyridine Copper(II) Complex Immobilized on Activated Multiwalled Carbon Nanotubes

AbstractA supported catalyst has been prepared by immobilization of a copper(II) complex of 4′‐phenyl‐2,2′:6′,2′′‐terpyridine on activated multiwalled carbon nanotubes [AMWCNTs‐O‐CuII‐PhTPY]. This heterogeneous catalyst was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), inductively coupled plasma (ICP) analysis, UV/vis and FT‐IR techniques. To ensure the efficiency and fidelity of the copper species, the implementation of three‐component strategies in click chemistry was tested. The catalyst enabled the development of one‐pot, two‐step, mild, and environmentally benign syntheses of diversely decorated 1,2,3‐triazoles from alkynes, epoxides or benzyl/alkyl halides, and sodium azide in water. The complex has high catalytic activity, regioselectivity, and was recycled five successive times. In another experiment, the vasorelaxing effect of the triazole products was studied in isolated rat thoracic aorta. All of the selected compounds are vasorelaxants, based on the IC50 values obtained, and the vasorelaxing potency and maximal response for three of the compounds are comparable to acetylcholine.

Photo-activated cytotoxicity of a pyrenyl-terpyridine copper(II) complex in HeLa cells

Terpyridine copper(II) complexes [Cu(L) 2](NO 3) 2, where L is (4′-phenyl)-2,2′:6′,2′′-terpyridine (ph-tpy in 1) and [4′-(1-pyrenyl)]-2,2′:6′,2′′-terpyridine (py-tpy in 2), are prepared, characterized and their photocytotoxic activity studied. The crystal structure of complex 1 shows distorted octahedral CuN 6 coordination geometry. The 1:2 electrolytic and one-electron paramagnetic complexes show a visible band near 650 nm in DMF–H 2O. The complexes show emission band at 352 nm for 1 and 425 nm for 2 when excited at 283 and 346 nm, respectively. The Cu(II)–Cu(I) redox couple is observed near −0.2 V versus SCE in DMF–0.1 M TBAP. The complexes are avid partial-intercalative binders to calf thymus DNA giving binding constant ( K b) values of ∼10 6 M −1. Complex 2 with its photoactive pyrenyl moiety exhibits significant photocleavage of pUC19 DNA in red light via singlet oxygen pathway. Complex 2 also exhibits significant photo-activated cytotoxicity in HeLa cancer cells in visible light giving IC 50 value of 11.9 μM, while being non-toxic in dark with an IC 50 value of 130.5 μM.

ChemInform Abstract: Reusable Polymer‐Supported Terpyridine Copper Complex for [3 + 2] Huisgen Cycloaddition in Water.

A polymer-supported terpyridine copper(I) complex was prepared and found to promote the Huisgen [3+2] cycloaddition reaction between azides and alkynes in water to give the corresponding triazoles with up to 87% isolated yield. This catalyst was recovered and reused several times without any loss in catalytic activity.

DNA photocleavage and anticancer activity of terpyridine copper(II) complexes having phenanthroline bases

Copper(II) complexes [Cu(ph-tpy)(B)](ClO 4) ( 1– 3), where ph-tpy is (4′-phenyl)-2,2′:6′,2″-terpyridine and B is N, N-donor phenanthroline base, viz. 1,10-phenanthroline (phen, 1), dipyridoquinoxaline (dpq, 2), and dipyridophenazine (dppz, 3), were prepared and characterized from analytical and spectral data. Complex 1, characterized by X-ray crystallography, shows a distorted square-pyramidal (4 + 1) CuN 5 coordination geometry having the tridentate ph-tpy ligand at the basal plane and bidentate phen bound to the axial-equatorial sites. The complexes display a d– d band near 650 nm in aqueous DMF. The complexes are avid binders to calf thymus DNA giving the binding order: 3 (dppz) > 2 (dpq) > 1 (phen). The dpq and dppz complexes show photo-induced DNA cleavage activity in red light via photo-redox pathway forming hydroxyl radicals. The cytotoxicity of the dppz complex 3 was studied by MTT assay in HeLa cancer cells. The IC 50 values are 3.7 and 12.4 μM in visible light of 400–700 nm and dark, respectively.

3+2] Cycloaddition Reaction with Polymer-Supported Terpyridine Copper Complex in Water

A polymer-supported terpyridine copper(I) complex was prepared and found to promote the Huisgen’s [3+2] cycloaddition reaction in water between azides and alkynes. Thus, terpyridine ligand was prepared from p-hydroxybenzaldehyde, propane sultone, and 2-acetylpyridine for 2 steps. Immobilization of terpyridine ligand onto a polystyrene-poly(ethylene glycol) (PS-PEG) resin through ionic bonds to sulfonate group took place and the complexation of amphiphilic PS-PEG resin-bound terpyridine ligand with Cu(I) underwent to give PS-PEG-terpyridine-Cu(I) complex 1 as green solid. This polymeric catalyst showed high catalytic activity for the Huisgen 1,3-dipolar cycloaddition reaction of organic azides with acetylenes. This catalyst was recovered and reused for several times without any loss of catalytic activity.

Reusable Polymer-Supported Terpyridine Copper Complex for [3+2] Huisgen Cycloaddition in Water

A polymer-supported terpyridine copper(I) complex was prepared and found to promote the Huisgen [3+2] cycloaddition reaction between azides and alkynes in water to give the corresponding triazoles with up to 87% isolated yield. This catalyst was recovered and reused several times without any loss in catalytic activity.

Anionic effects on the formation of tridentate 4′-chloro-2,2′:6′,2″-terpyridine copper(II) complexes having 1:1 or 1:2 ratio of metal and ligand and their crystal symmetry

A facile synthetic procedure has been used to prepare one five-coordinate and four six-coordinate copper(II) complexes of 4′-chloro-2,2′:6′,2″-terpyridine (tpyCl) ligand with different counterions ( SO 4 2 - , NO 3 - , BF 4 - , PF 6 - , and ClO 4 - ) in high yields. They are formulated as [Cu(tpyCl- κ 3N,N ′ ,N′′)(SO 4- κO)(H 2O- κO)] · 2H 2O ( 1), trans-[Cu(tpyCl- κ 3N,N ′ ,N″)(NO 3- κO) 2(H 2O- κO)] ( 2), [Cu(tpyCl- κ 3N,N ′ ,N″) 2](BF 4) 2 ( 3), [Cu(tpyCl- κ 3N,N ′ ,N″) 2](PF 6) 2 ( 4) and [Cu(tpyCl- κ 3N,N ′ ,N″) 2](ClO 4) 2 ( 5) and versatile interactions in supramolecular level including coordinative bonding, O–H⋯O, O–H⋯Cl, C–H⋯F, and C–H⋯Cl hydrogen bonding, π –π stacking play essential roles in forming different frameworks of 1– 5. It is concluded that the difference of coordination abilities of the counterions used and the experimental conditions codominate the resulting complexes with 1:1 or 1:2 ratio of metal and ligand.

Helical and polymeric nanostructures assembled from benzene tri- and tetracarboxylic acids associated with terpyridine copper(ii) complexes

A ladder-like framework was derived from benzene-1,2,4,5-tetracarboxylic acid with Cu(II) and terpyridine; whereas with benzene-1,3,5-tricarboxylic acid, a helical structure was formed with two CO2- groups bridging opposing (terpyridine)Cu(II) units and the other CO2H connecting the helical cylinders via H-bonding.

Efficient site-specific cleavage of RNA using a terpyridine–copper(II) complex joined to a 2′-O-methyloligonucleotide by a non-flexible linker

A terpyridine–Cu(II) complex conjugated to an antisense 2′-O-methyloligonucleotide at the 5′-end cleaved RNA predominantly at the site opposite the 5′-end in moderate yield, but the cleavage yield increased by more than two-fold when a 2′-O-methyloligonucleotide was allowed to bind to the single-stranded region of the RNA-antisense complex.

Bonding properties of Cu(II)N chromophores: preparation, structure and spectroscopic properties of mixed ligand 2,2′:6′,2″-terpyridine copper(II) complexes. Molecular structures of [Cu(terpyridine)(4-methylimidazole)(H 2O)(BF 4)] (BF 4) and [Cu(terpyridine)(3-methylpyridine)(BF 4) 2)

Mixed ligand 2,2′:6′,2″-terpyridine copper(II) complexes of the Cu(terpy)L(BF 4) 2·nH 2O type, where terpy stands for terpyridine, and L for imidazole ( n = 1), N-methylimidazole ( n = 1), 4-methylimidazole ( n = 1), benzimidazole ( n = 1), pyridine ( n = 0), 3-methylpyridine ( n = 0), 4-methylpyridine ( n = 1), and NH 3 ( n = 0), have been synthesized and characterized by elemental analyses, and electronic, vibrational, and EPR spectroscopic measurements. The X-ray crystal structures of [Cu(terpy)(4MImH)(H 2O) (BF 4)](BF 4) ( 1) and [Cu(terpy)(3Mpy)(BF 4)] ( 2) (4MImH = 4-methylimidazole; 3Mpy = 3-methylpyridine) have been determined from three-dimensional X-ray diffraction data. Both complexes comprise [4+1 + 1] copper units where the terpy and the unidentate N-donor ligand bind to the central copper ion forming a square plane. The CuN bond lengths along the unidentate ligand are considerably shorter than the others. The dihedral angle between the CuN 4 coordination plane and the imidazole nucleus in 1 is 85.3°; the corresponding angle between the CuN 4 plane and the pyridine nucleus in 2 is 66.2°. Similar structures with a CuN 4 coordination plane are proposed for other complexes based on spectroscopic data. The sequence of the d orbitals has been deduced from Gausian analysis of the LF spectra as d x 2−y 2 > d z 2 > d xy > d yz > d xz, where x axis is along the CuN(unidentate) on the CuN 4 plane. The bonding properties of these complexes are elucidated and discussed with reference to the electronic structures.