Copper(II) complexes of 1,10-phenanthroline-derived ligands: studies on DNA binding properties and nuclease activity

A series of copper(II) complexes of the type [Cu(L)]2+, where L = N,N'-dialkyl-1,10-phenanthroline-2,9-dimethanamine and R = methyl (L1), n-propyl (L2), isopropyl (L3), sec-butyl (L4), or tert-butyl (L5) group, have been synthesized. The interaction of the complexes with DNA has been studied by DNA fiber electron paramagnetic resonance (EPR) spectroscopy, emission, viscosity and electrochemical measurements and agarose gel electrophoresis. In the X-ray crystal structure of [Cu(HL2)Cl2]NO3, copper(II) is coordinated to two ring nitrogens and one of the two secondary amine nitrogens of the side chains and two chloride ions as well and the coordination geometry is best described as trigonal bipyramidal distorted square based pyramidal (TBDSBP). Electronic and EPR spectral studies reveal that all the complexes in aqueous solution around pH 7 possess CuN3O2 rather than CuN4O chromophore with one of the alkylamino side chain not involved in coordination. The structures of the complexes in aqueous solution around pH 7 change from distorted tetragonal to trigonal bipyramidal as the size of the alkyl group is increased. The observed changes in the physicochemical features of the complexes on binding to DNA suggest that the complexes, except [Cu(L5)]2+, bind to DNA with partial intercalation of the derivatised phen ring in between the DNA base pairs. Electrochemical studies reveal that the complexes prefer to bind to DNA in Cu(II) rather than Cu(I) oxidation state. Interestingly, [Cu(L5)]2+ shows the highest DNA cleavage activity among all the present copper(II) complexes suggesting that the bulky N-tert-butyl group plays an important role in modifying the coordination environment around the copper(II) center, the Cu(II)/Cu(I) redox potential and hence the formation of activated oxidant responsible for the cleavage. These results were compared with those for bis(1,10-phenanthroline)copper(II), [Cu(phen)2]2+.     

Antibacterial Co(II), Ni(II), Cu(II) and Zn(II) complexes of Schiff bases derived from fluorobenzaldehyde and triazoles

Antibacterial Schiff bases derived from 1,2,4-triazoles as well as their metal complexes incorporating cobalt(II), nickel(II), copper(II) and zinc(II) have been synthesized and characterized. Physico-chemical studies suggest that an octahedral geometry for the cobalt(II), nickel(II) and zinc(II)and square-planer geometry for the copper(II) complexes. These complexes have been screened for antibacterial activity against three Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis) and two Gram-negative (Salmonella typhi and Pseudomonas aeruginosa) bacterial strains, and results compared with the activity of the free ligands. The metal complexes were found to be more potent against one or more bacterial strains than the free ligands.     

Antibacterial Co(II), Ni(II), Cu(II) and Zn(II) Complexes of Schiff bases Derived from Fluorobenzaldehyde and Triazoles

Antibacterial Schiff bases derived from 1,2,4-triazoles as well as their metal complexes incorporating cobalt(II), nickel(II), copper(II) and zinc(II) have been synthesized and characterized. Physico-chemical studies suggest that an octahedral geometry for the cobalt(II), nickel(II) and zinc(II)and square-planer geometry for the copper(II) complexes. These complexes have been screened for antibacterial activity against three Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis) and two Gram-negative (Salmonella typhi and Pseudomonas aeruginosa) bacterial strains, and results compared with the activity of the free ligands. The metal complexes were found to be more potent against one or more bacterial strains than the free ligands.     

Structural diversity in five-coordinate nickel(II) complexes of the tripyrrin ligand

Three different five coordinate nickel(II) complexes of tripyrrin ligands with chloro, oxalato and nitrato anionic ligands were obtained by ligand exchange reactions from respective trifluoroacetato species prepared in situ. Crystallographic studies of these compounds revealed different coordination geometries as well as different packing pattern. In the solid, the chloride complex accepts one water ligand to form a distorted trigonal bipyramid with two N donor centers in apical and one in an equatorial position. The molecules are organized in the crystal via hydrogen bonds, resulting in endless chains. Oxalate serves as a bridging ligand between two nickel(II) tripyrrins. Again the coordination of nickel(II) is found to be trigonal bipyramidal but with two equatorial and one apical nitrogen donors. The discrete dinuclear complexes are arranged in the crystal in a way as to form channels filled with toluene molecules. The nitrate species displays a η² bound nitrate ligand and short contacts between the nickel(II) center and an ethyl substituent of a neighboring molecule. The complex shows an unusually distorted molecular structure and unexpected differences in the two Ni-O bond lengths.     

Triazamacrocyclic complexes with 8- and 9-membered chelate rings. Preparation, structures and agostic interactions in complexes of 1,5,9-triazacyclotetradecane and 1,5,9-triazacyclopentadecane

Cobalt(II), copper(II) and nickel(II) complexes of the ligands 1,5,9-triazacyclotetradecane (tatd) and 1,5,9-triazacyclopentadecane (tapd), which have 8- and 9-membered chelate rings, respectively, have been prepared and characterised. Crystal structures of [Ni(tatd)(NCS)₂]·H₂O and [Co(tatd)(NCS)₂] have been determined. The nickel(II) complex has a distorted square pyramidal geometry and the cobalt(II) complex has a distorted trigonal bipyramidal geometry. Agostic interactions between a hydrogen on the central carbon of the 8-membered chelate ring and the metal ion are observed in both complexes.     

Preparation and spectroscopic properties of cobalt(III), nickel(II), copper(II) and zinc(II) complexes with a novel saturated macrocyclic ligand: 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22-docosahydrodibenzo-[b,i][1,4,8,11]tetraazacyclotetradecine

1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19, 20,21,22-Docosahydrodibenzo[b,i] [1,4,8,11] tetraazacyclotetradecine was prepared by hydrogenation of the benzo-analogue. Five isomers are feasible as a result of this hydrogenation but only two have been isolated: isomer A (melting point 158.5– 161.0 °C) and isomer B (melting point 194.5– 196.0 °C). The ¹³C NMR study was initiated to clear up the conformational differences between isomers. The cobalt(III), nickel(II), copper(II) and zinc(II) complexes of isomers A and B were prepared and investigated by near-ultraviolet, visible, infrared, NMR and ESR measurements. The ligand-field band in the 15 000-30 000 cm⁻¹ region for the cobalt(III), nickel(II) and copper(II) complexes provided information on their geometry around the central metal atom. That is to say, the cobalt(III) complexes are subjected to the octahedral ligand-field with axial elongation. The copper(II) complexes and the nickel- (II) complex of isomer A are subjected to the square- planar ligand-field in these complexes. The ligand- field bands for the nickel(II)complex of isomer B display the square-planar-distorted octahedral equilibrium in the coordinating solvent. ESR measurements for the copper(II) complexes also presented the spin Hamiltonian parameters in accord with the square- planar coordination. A strong band appearing at ca. 3200 cm⁻¹ was assigned to the N-H stretching mode and this band was slightly shifted to lower frequency upon metal coordination. The vibrational spectra and the conductance data provided evidences for the formation of the complexes with perchlorate ion as the counter ion. ¹³C NMR suggest that the complexes of isomer A are the cis-syn-cis form and the complexes of isomer B are the cis-anti-cis form.     

Metal complexes of the schiff bases 2-pyridinylhydrazine and 2-quinolinyl-hydrazine with 2-pyridinecarboxaldehyde N-oxide,including some N-oxide-bridged antiferromagnetic complexes of cobalt(II) and nickel(II)

Metal complexes of 2-pyridine carboxaldehyde 2′-pyridinylhydrazone 1-oxide (poph) and 2-pyridinecarboxaldehyde 2′-quinolinylhydrazone 1-oxide (poqh) are reported with copper(II), nickel(II), cobalt(II), iron(II) and manganese(II). Each ligand appears to function as an ONN donor, via the pyridine N-oxide oxygen, the imine nitrogen, and a pyridine or quinoline nitrogen. The complexes have been characterised by magnetic susceptibility measurements to liquid nitrogen temperature, and also by electronic, infrared, X-ray powder diffraction, and Mössbauer spectra. No magnetic interaction was detected with the copper(II) complexes. All the complexes of metal nitrates appear to be monomers.The complexes of poph with the halides and thiocyanates of nickel(II) and cobalt(II) appear to be six-coordinate and N-oxide-bridged; they exhibit varying degress of antiferromagnetic interaction and the magnetic data for the nickel(II) complexes have been fitted to various models. In contrast, the bulky ligand poqh produces halide-bridged six-coordinate nickel(II) complexes and monomeric five-coordinate cobalt(II) complexes.This behaviour by poqh resembles that of the related NNN ligands paphy and paqhy, which are the Schiff bases of 2-pyridinecarboxaldehyde with 2-pyridinylhydrazine and 2-quinolinylhydrazine, respectively.     

Stability constants of thiocyanato complexes of cobalt(II), nickel(II) and copper(II) in methanol.

A spectrophotometric study of cobalt(II), nickel(II) and copper(II) thiocyanato complexes was carried out in methanol at 25 degrees C and at a constant ionic strength of 1 M. Under the experimental conditions, two mononuclear complexes are identified with each of the three metal ions. Their stability constants are determined with a recent PC program SIRKO and the calculated values are: for cobalt, log beta 1 = 1.6, log beta 2 = 2.7; for nickel, log beta 1 = 1.8, log beta 2 = 3.0; and for copper, log beta 1 = 3.0, log beta 2 = 3.6.     

Synthesis and characterisation of copper(II), zinc(II) and cobalt(II) complexes of salicylglycine, a metabolite of aspirin

Copper(II), nickel(II) and cobalt(II) complexes of the aspirin metabolite salicylglycine (H₂L), of stoichiometry M(HL)₂·solvate, have been prepared and characterised. In these complexes salicylglycinate is coordinated to the metal via its carboxylato group and possibly also its amide oxygen in the copper(II) complex. Under basic conditions copper(II) forms the complex Cu(LH₋₁)·2H₂O·MeOH, in which the ligand is coordinated to the metal via its carboxylate and phenolate oxygen atoms and the deprotonated peptide nitrogen atom.     

Design,synthesis, and biological properties of triazole derived compounds and their transition metal complexes

Triazole derived Schiff bases and their metal complexes (cobalt(II), copper(II), nickel(II), and zinc(II)) have been prepared and characterized using IR, ¹H and ¹³C NMR, mass spectrometry, magnetic susceptibility and conductivity measurements, and CHN analysis data. The structure of L², N-[(5-methylthiophen-2-yl)methylidene]-1H-1,2,4-triazol-3-amine, has also been determined by the X-ray diffraction method. All the metal(II) complexes showed octahedral geometry except the copper(II) complexes, which showed distorted octahedral geometry. The triazole ligands and their metal complexes have been screened for their in vitro antibacterial, antifungal, and cytotoxic activity. All the synthesized compounds showed moderate to significant antibacterial activity against one or more bacterial strains. It is revealed that all the synthesized complexes showed better activity than the ligands, due to coordination.     

Cobalt(II) and nickel(II) complexes with nitrogen-sulfur tripod ligands. Crystal and molecular structure of the five-coordinate complex bromotris(2-tert-butylthioethyl)aminecobalt(II) hexafluorophosphate (NS3Br donor set)

The tripod ligands tris(2-alkylthioethyl)amine, with alkyl = ethyl, iso-propyl, and tert-butyl, give with cobalt(II) and nickel(II) halides high-spin complexes with formulae [MLX₂], [MLX]Y, and [MLX]₂[MX₄] (where X = Cl, Br, I; Y = BPh₄, PF₆). The nickel complexes are either six- or five-coordinate: the coordination number decreases as the bulkiness of the alkyl group bound to the sulfur is increased. All the cobalt complexes contain the five-coordinate cation [CoLX]⁺. The crystal and molecular structure of the [Co(NS₃-t-Bu)Br]PF₆ complex has been determined by standard X-ray methods, and refined to R = 0.061. The crystals are monoclinic, space group P2¹/n. The unit cell dimensions are: a = 27.420 (2), b = 11.923 (4), c = 17.082 (1) Å, β = 102.40 (1)°, Z = 8. The complex cation has a trigonal bipyramidal geometry with the nitrogen and bromine atoms at the apexes, and the three sulfur atoms in the equatorial plane. The tetrahedral distortion is relatively small (mean BrCoS angle = 98.5°), and similar to that found for the [Co (Me₆tren)Br]Br complex [Me₆tren = tris(2-dimethylaminoethyl)amine).     

Synthesis and characterization of a new binucleating schiff base macrocycle and its nickel(II) and copper(II) complexes

A new binucleating ligand, m-xyl-bis(3-bae)) and its copper(II) and nickel(II) complexes have been prepared and characterized by various physical techniques. Data for the complexes indicate that they both have square-planar geometries. High resolution ¹H and ¹³C NMR confirm the square-planar geometry of the binuclear nickel(II) complex is maintained in non-coordinating solvents. The magnetic moment of the copper(II) complex is typical of square-planar complexes and the EPR spectrum in solution indicates the absence of any magnetic coupling between metal centers. In addition, both metal complexes display irreversible electrochemical behavior on various electrode surfaces.     

Antibacterial cobalt(II), nickel(II) and zinc(II) complexes of nicotinic acid-derived Schiff-bases

Nicotinic acid derived Schiff bases and their transition metal [cobalt(II), nickel(II) and zinc(II)] complexes have been prepared and characterized by physical, spectral and analytical data. The Schiff bases act as deprotonated tridentate ligands for the complexation of the above mentioned metal ions. These complexes, possessing the general formula [M(L)2] [where M = Co(II), Ni(II) and Zn(II) and L = HL1-HL4] showed an octahedral geometry of the metal ions. For determining the effect of metal ions upon chelation, the Schiff bases and their complexes have been screened for antibacterial activity against several pathogenic strains of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. The new metal derivatives reported here were more bactericidal against one or more bacterial species as compared to the uncomplexed Schiff bases.     

Preparation and characterization of cobalt(II), nickel(II) and copper(II) complexes with water-soluble macrocyclic N4-ligands: 6,15-diethyl-4,13-dihydro-1,10-dimethyl-(E)-dipyridinio [b,i] [1,4,8,11] tetraazacyclotetradecine iodide or methyl sulfate

The mixture of 6,15-diethyl-4,13-dihydro-(E)-dipyrido [b,i] [1,4,8,11] tetraazacyclotetradecine (2-E) and 6,15-diethyl-4,13-dihydro-(Z)-dipyrido [b,i][1,4,8,11] tetraazacyclotetradecine (2-Z) was prepared by cyclization of 3,4-diaminopyridine and 2-ethyl-3-ethoxyacrolein. Two kinds of isomers were separated by repeated recrystallization from chloroform. Methylation of pyridine comprised in 2-E using iodomethane or dimethyl sulfate afforded the corresponding dimethylated product (2-E-I or 2-E-S), which is soluble in water. The cobalt(II), nickel(II) and copper(II) complexes of 2-E-I and 2-E-S were prepared. The absorption bands appearing in the energy range greater than 18 000 cm⁻¹ were attributed to the π → π* transitions within a ligand molecule and CT transitions from metal to ligand. Since the d → d* bands for nickel(II) and copper(II) complexes were obscured by the π → π* and CT bands, no significant absorption bands were found in the region more than 18000 cm⁻¹. One of the d → d* bands for the cobalt(II) complex was observed at around 13 000 cm⁻¹. These complexes assume the square- planar structures. A strong IR band due to the CN stretching mode of the macrocycle moiety was observed at ca. 1640 cm−1 and shifted slightly toward lower energy upon metal-coordination, cis (2-Z) and trans (2-E) isomers in the present macrocycle can be judged by the amine proton signals of NMR spectra. All proton signals except for amine protons show downfield shifts due to the deshielding effect of the positive charge provided by methylation of pyridine contained in the metal-free macrocycle. Upon formation of the nickel(II) complex all proton signals, except the aromatic protons adjacent to the nitrogen atom of a pyridine ring, also show a downfield shift, which is attributed to the deshielding effect based on the positive charge given by nickel(II). The intensity change of the electronic spectrum at 425 nm is available for the determination of copper(II) concentrations in the aqueous solution using the water-soluble macrocycles (2-E-I and 2-E-S) and a good linear correlation is observed up to 8 × 10⁻⁶ mol dm⁻³.     

Solvent effects on the stability of nifuroxazide complexes with cobalt(II), nickel(II) and copper(II) in alcohols

A spectrophotometric study of the complexation of nifuroxazide with cobalt(II), nickel(II) and copper(II) was carried out in different alcohols. The formation of a complex in each case is reported and their stability constants have been calculated. For a given solvent, the stability of the complexes increases from cobalt to copper. In the case of copper(II), the stability varies as an inverse function of the dielectric constant of the solvent. A possible structure of the complex is proposed.     

Antibacterial and antifungal metal based triazole Schiff bases

A new series of four biologically active triazole derived Schiff base ligands (L¹–L⁴) and their cobalt(II), nickel(II), copper(II) and zinc(II) complexes (1–16) have been synthesized and characterized. The ligands were prepared by the condensation reaction of 3-amino-5-methylthio-1H-1,2,4-triazole with chloro-, bromo- and nitro-substituted 2-hydroxybenzaldehyde in an equimolar ratio. The antibacterial and antifungal bioactivity data showed the metal(II) complexes to be more potent antibacterial and antifungal than the parent Schiff bases against one or more bacterial and fungal species.     

Cobalt(II), nickel(II), copper(II) and zinc(II) complexes with an open-chain pentadentate nitrogen ligand

The open-chain, potentially, pentadentate, ligan 1,11-bis(dimethylamino)-3,6,9-trimethyl-3,6,9,-triazaundecane (Me₇tetren) forms a series of metal complexes having the general formula [M(Me₇tetren)]Y₂ (Y = 1, M = Co, Ni; Y = ClO₄, M = Co, Ni, Cu, Zn). On the basis of their physical properties, it is suggested that all these compounds contains isostructural five-coordinate [M(Me₇tetren)]²⁺ cations, the ligand acting as pentadentate. These complexes react in solution with thiocyanate ion to give mono- and, with exception of copper(II), di-thiocyanato five- and six-co-ordinate derivatives. Mono-thiocyanato derivatives of cobalt(II), nickel(II) and zinc(II) have been isolated as tetraphenylborate salts. Cobalt(II) and nickel (II) di-thiocyanato derivatives have been also isolated. Results are discussed in terms of the steric requirements of the ligand and electronic properties of the metal ions.     

Copper(II) complexes of N-heteroaromatic hydrazones: Synthesis, X-ray structure, magnetic behavior, and antibacterial activity

Three novel copper(II) complexes as condensation derivatives of 2-pyridinecarboxaldehyde, 2-acetylpyridine or 2-quinolinecarboxaldehyde with ethyl hydrazinoacetate hydrochloride were synthesized. X-ray crystal structures of all three complexes were determined. Crystallographic data indicate a common basis of the structures with some major differences. Both pyridine derivatives form complexes of the type [CuCl₂L] with distorted square-planar geometry around copper(II), but show a decisive difference in the side chain orientation. The quinoline derivative forms a dimeric complex of type [Cu₂Cl₄L₂] with distorted trigonal bipyramidal geometry around copper(II), but a rather short Cu···Cu contact, which is reflected in its magnetic properties. All three complexes showed antibacterial activity.     

Syntheses and characterization of mono- and di-N-hydroxyethylated tetraaza macrocycles containing eight C-methyl groups and their nickel(II) and copper(II) complexes

New partially N-hydroxyethylated 14-membered tetraaza macrocycles 1,8-bis(2-hydroxyethyl)-3,5,7,7,10,12,14,14-octamethyl-1,4,8,11-tetraazacyclotetradecane (L²) and 1-(2-hydroxyethyl))-3,5,7,7,10,12,14,14-octamethyl-1,4,8,11-tetraazacyclotetradecane (L³) have been synthesized selectively by the one-step reaction of 2,5,5,7,9,12,12,14-octamethyl-1,4,8,11-tetraazacyclotetradecane (L¹) with 2-hydroxyethyl bromide. The complexes [NiL³]²⁺, [CuL²]²⁺, and [CuL³]²⁺ have been prepared and characterized. The complex [CuL²](ClO₄)₂ has a square-pyramidal coordination geometry with one apical oxygen atom; only one of the two hydroxyethyl groups is coordinated to the metal ion. Electronic absorption spectra of [CuL³](ClO₄)₂ containing one hydroxyethyl pendant arm indicate that the geometry is similar to that of [CuL²](ClO₄)₂. Unexpectedly, the nickel(II) complex [NiL³](ClO₄)₂ has a severely distorted trigonal bipyramidal coordination geometry with the oxygen atom of the pendant arm at the equatorial position. The Ni---O bond distance of the nickel(II) complex is shorter, or not longer, than the Ni---N bond distances. The ligand in [CuL²]²⁺ is in the RRSS (trans-III) configuration, as usual, whereas that in [NiL³]²⁺ has the RRRR (trans-V) conformation. The coordination geometry and properties of [NiL³]²⁺ are quite different from those reported for other related nickel(II) complexes containing one functional pendant arm.     

Theoretical,in Vitro Antiproliferative,and in Silico Molecular Docking and Pharmacokinetics Studies of Heteroleptic Nickel(II) and Copper(II) Complexes of Thiosemicarbazone-Based Ligands and Pefloxacin

Twelve new heteroleptic nickel(II) and copper(II) complexes of the type [M(L^1–6)(Pfx)₂] ( 1 – 12 ), where L^1–6=2-benzylidenehydrazinecarbothioamide (L¹), 2-benzylidene-N-methylhydrazinecarbothioamide (L²), 2-benzylidene-N-phenylhydrazinecarbothioamide (L³), 2-(4-methylbenzylidene)hydrazinecarbothioamide (L⁴), 2-(4-methylbenzylidene)-N-methylhydrazinecarbothioamide (L⁵) and 2-(4-methylbenzylidene)-N-phenylhydrazinecarbothioamide (L⁶), Pfx=pefloxacin and M=Ni(II) or Cu(II) have been synthesised, and their structures were confirmed by different spectral techniques. The spectral data and density functional theory (DFT) calculations supported the bonding of pefloxacin drug molecule via one of the carboxylate oxygen atoms and the pyridone oxygen atom, and the thiosemicarbazone ligand via the imine nitrogen and the thione sulfur atoms with the metal(II) ion, forming distorted octahedral geometry. In vitro antiproliferative activity of the synthesized complexes was evaluated against three human breast cancer (T47D, estrogen negative (MDA-MB-231) and estrogen positive (MCF-7)) as well as non-tumorigenic human breast epithelial (MCF-10a) cell lines, which showed the higher activity for the copper(II) complexes. The interaction of the synthesized complexes with an oncogenic protein H-ras (121 p) was explored by in silico molecular docking studies. Further, in silico pharmacokinetics and ADMET parameters were also analysed to predict the drug-likeness as well as non-toxic and non-carcinogenic behavior, and safe oral administration of the complexes.