Electrochemical,magnetic, catalytic and DNA cleavage studies of binuclear copper(II) complexes derived from pendant substituted tetraaza macrobicyclic compartmental ligands

A series of macrobicyclic unsymmetrical binuclear copper(II) complexes of compartmental ligands were synthesized from the Schiff base condensation of 1,8[N,N′-bis{(3-formyl-2-hydroxy-5-methyl)benzyl}]-1,4,8,11- tetraaza-5,5,7,12,12,14-hexa methylcyclotetradecane with diamines like 1,2-diamino ethane, 1,3-diamino propane, 1,4-diaminobutane, 1,2-diaminobenzene and 1,8-diaminonaphthalene. The complexes were characterized by elemental and spectral analysis. Electrochemical studies of the copper(II) complexes show two irreversible one-electron reduction processes around E¹_pc = −0.70 to −1.10 V and E²_pc = −0.98 to −1.36 V. ESR spectra of the binuclear copper(II) complexes show a broad signal at g = 2.10 and μ_eff values in the range 1.46–1.59 BM, which convey the presence of antiferromagnetic coupling. Cryomagnetic investigation of the binuclear complexes [Cu₂L³(ClO₄)](ClO₄) and [Cu₂L⁴(ClO₄)](ClO₄) show that the observed −2J values are 144 and 216 cm⁻¹, respectively. The observed initial rate (V_in) for the catalytic hydrolysis of p-nitrophenyl phosphate by the binuclear copper(II) complexes were in the range 1.8 × 10⁻⁵ to 2.1 × 10⁻⁵ Ms⁻¹. The initial rate (V_in) for the catalytic oxidation of catechol to o-quinone by the binuclear copper(II) complexes were in the range 2.7 × 10⁻⁵ to 3.5 × 10⁻⁵ Ms⁻¹. The copper(II) complexes have been found to promote cleavage of plasmid pBR 322 DNA from the supercoiled form I to the open circular form II.     

DNA binding,cleavage, and cytotoxicity of binuclear phenolate nickel(II) complexes

Three binuclear phenolate complexes, [Ni₂(L¹)₂(OAc)](BPh₄)·DMF (1), [Ni₂(L²)₂(OAc)](BPh₄) (2), and [Ni₂(L³)₂(OAc)](OH)·3H₂O (3), where L¹ = 2-{[bis-(2-hydroxy-ethyl)-amino]-methyl}-4-methyl-phenol, L² = 2-{[bis-(2-hydroxy-ethyl)-amino]-methyl}-4-methoxy-phenol, and L³ = 2-{[bis-(2-hydroxy-ethyl)-amino]-methyl}-4-tert-butyl-phenol), have been synthesized. Single-crystal diffraction reveals that all the metal atoms are in a distorted octahedral geometry. The interactions of the complexes with calf thymus DNA (CT-DNA) have been investigated by UV–vis absorption, fluorescence emission, and circular dichroism spectroscopy and viscosity measurements. Furthermore, DNA cleavage mechanism shows that the complexes may be capable to promote DNA cleavage through oxidative DNA damage pathway, which is indicative of the involvement of hydroxyl radical, singlet oxygen, or singlet oxygen-like entity in the cleavage process. Cytotoxicity studies on the Hela and MCF-7 cancer cell lines show that complexes 1–3 exhibit excellent activity toward the tested tumor cell lines with respect to the standard drug carboplatin, revealing that they have the potential to act as effective metal-based anticancer drugs.     

New anthracene based Schiff base ligands appended Cu(II) complexes: Theoretical study,DNA binding and cleavage activities

New anthracene based Schiff base ligands L ¹ and H( L ² ), their Cu(II) complexes [Cu( L ¹ )Cl₂] ( 1 ) and [Cu( L ² )Cl] ( 2 ) , (where L ¹  = N¹,N²‐bis(anthracene‐9‐methylene)benzene‐1,2‐diamine, L ²  = (2Z,4E)‐4‐(2‐(anthracen‐9‐ylmethyleneamino)phenylimino)pent‐2‐en‐2‐ol) have been prepared and characterized by elemental analysis, NMR, FAB‐mass, EPR, FT‐IR, UV–Vis and cyclic voltammetry. The electronic structures and geometrical parameters of complexes 1 and 2 were analyzed by the theoretical B3LYP/DFT method. The interaction of these complexes 1 and 2 with CT‐DNA has been explored by using absorption, cyclic voltammetric and CD spectral studies. From the electronic absorption spectral studies, it was found that the DNA binding constants of complexes 1 and 2 are 8.7 × 10³ and 7.0 × 10⁴ M^?1, respectively. From electrochemical studies, the ratio of DNA binding constants K₊/K₂₊ for 2 has been estimated to be >1. The high binding constant values, K₊/K₂₊ ratios more than unity and positive shift of voltammetric E_1/2 value on titration with DNA for complex 2 suggest that they bind more avidly with DNA than complex 1 . The inability to affect the conformational changes of DNA in the CD spectrum is the definite evidences of electrostatic binding by the complex 1 . It can be assumed that it is the bulky anthracene unit which sterically inhibits these complexes 1 and 2 from intercalation and thereby remains in the groove or electrostatic. The complex 2 hardly cleaves supercoiled pUC18 plasmid DNA in the presence of hydrogen peroxide. The results suggest that complex 2 bind to DNA through minor groove binding.     

Synthesis, structural and magnetic properties of diphenoxo-bridged binuclear mixed-ligand Cu(II) complexes

The copper(II) complexes [Cu₂(phen)₂(HL¹)₂] (ClO₄)₂ (1) and [Cu₂(phen)₂(HL²)₂] (ClO₄)₂ (2) synthesized from two potentially tridentate ligands N-(2-hydroxybenzyl) propanolamine (H₂L¹) and N-(5-methyl-2-hydroxybenzyl) propanolamine (H₂L²) have centrosymmetric bis(μ₂-phenoxo)-bridged dicopper(II) structures. Variable temperature magnetic measurements have revealed the existence of relatively weak antiferromagnetic interactions (1: 2J=−212.5, 2: 2J=−337.0 cm⁻¹) with respect to the bridging angles (1: θ=101.47(18)°, 2: θ=102.79(12)°). The results suggest that the distortion index of the Cu(II) atoms (1: τ=0.73, 2: τ=0.53) may be the major factor governing the spin coupling between the copper(II) centers of these diphenoxo-bridged binuclear complexes. The coordination moieties of complex 1 are connected into a 1D linear structure via intermolecular hydrogen bonds between alkoxyl, amine, and perchlorate groups.     

EXAFS study of binuclear hydroxo-bridged copper(II) complexes

Extended X-ray absorption fine structure (EXAFS) measurements have been recorded at the K-edge of copper in binuclear monohydroxo-bridged copper(II) complexes [(bpy)₂Cu–OH–Cu(bpy)₂](ClO₄)₃ (1) and [(phen)₂Cu–OH–Cu(phen)₂](C1O₄)₃ (2) and dihydroxo-bridged copper(II) complexes [Cu₂(μ–OH)₂(bipy)₂]SO₄?·?5H₂O (3) and [Cu₂(μ–OH)₂(phen)₂]SO₄?·?5H₂O (4) (where bpy and phen are 2,2′-bipyridine and 1,10-phenanthroline, respectively) using the dispersive EXAFS beamline at 2?GeV Indus-2 synchrotron source at RRCAT, Indore, India. The EXAFS data have been analyzed using the software, Athena and Artemis. Theoretical models have been generated for 1 and 3 using available crystallographic data and then fitted to their experimental EXAFS data to obtain the structural parameters, which include bond-lengths, coordination numbers, and thermal disorders. The results obtained have been found to be comparable with their crystallographic results. As the crystallographic data for 2 and 4 are not available in the literature, we have determined their structural parameters by fitting their experimental EXAFS data with the same theoretical models which were generated for their corresponding analogous complexes 1 and 3, respectively. The structural parameters thus determined have been reported. Also, on the basis of the analysis of the EXAFS data, these four complexes have been shown to be binuclear, i.e. they contain two metals. Further, the values of the chemical shifts suggest that copper is in +2 oxidation state in these complexes.     

Synthesis and DNA cleavage properties of ternary Cu(II) complexes containing histamine and amino acids

The ternary complexes of [Cu^II(Hist)(Tyr)]⁺1 and [Cu^II(Hist)(Trp)]⁺2 have been synthesized, structurally characterized and their DNA binding and cleavage abilities probed. The intrinsic binding constants (K_b) for complexes/CT-DNA were also determined (K_b = 2.7 × 10² for complex 1 and K_b = 2.2 × 10² for complex 2). These complexes exhibit their nuclease activity on plasmid DNA, which seems to depend on the nature of the aromatic moiety. The DNA hydrolytic cleavage rate constants were also determined for complexes 1 and 2, which are 0.91 and 0.79 h⁻¹, respectively.     

New acyclic Schiff-base copper(II) complexes and their electrochemical,catalytic, and antimicrobial studies

A new series of acyclic mononuclear copper(II) complexes have been prepared by Schiff-base condensation derived from 5-methylsalicylaldehyde, diethylenetriamine, tris(2-aminoethyl) amine, triethylenetetramine, N,N-bis(3-aminopropyl)ethylene diamine, N,N-bis(aminopropyl) piperazine, and copper perchlorate. All the complexes were characterized by elemental and spectral analyses. Electronic spectra of the complexes show a d–d transition in the range 500–800?nm, electrochemical studies of the complexes show irreversible one-electron-reduction process around ?1.10 to ?1.60?V. The reduction potential of the mononuclear copper(II) complexes shifts toward anodic direction upon increasing the chain length of the imine compartment. ESR spectra of the mononuclear copper(II) complexes show four lines, characteristic of square-planar geometry, with nuclear hyperfine spin 3/2. The copper(II) complexes show a normal room temperature magnetic moment value μ _eff?=?1.72–1.76?BM, close to the spin-only value of 1.73?BM. Electrochemical and catalytic studies of the complexes were compared on the basis of increasing the chain length of the imine compartment. All the complexes were screened for antifungal and antibacterial activities.     

Synthesis, characterization, DNA binding and cleavage studies of chiral Ru(II) salen complexes

Interaction of chiral Ru(II) salen complexes (S)-1 and (R)-1 with Calf Thymus DNA (CT-DNA) was studied by absorption spectroscopy, competitive binding study, viscosity measurements, CD measurements, thermal denaturation study and cleavage studies by agarose gel electrophoresis. The DNA binding affinity of (S)-1 (6.25 × 10³ M⁻¹) was found to be greater than (R)-1 (3.0 × 10³ M⁻¹). The antimicrobial studies of these complexes on five different gram (+)/(−) bacteria and three different fungal organisms showed selective inhibition of the growth of gram (+) bacteria and were not affective against gram (−) and fungal organisms. Further, the (S)-1 enantiomer inhibited the growth of organisms to a greater extent as compared to (R)-1 enantiomer.     

Synthesis,spectral characterization,antioxidant, anticancer in vitro,and DNA cleavage studies of a series of ruthenium(II) complexes bearing Schiff base ligands

Ruthenium(II) complexes with 2-acetylpyridine-thiosemicarbazones (L¹–L⁴) were synthesized and characterized by analytical and spectral (FT-IR, UV–vis, NMR [¹H, ¹³C and ³¹P], and ESI-Mass) methods. Systematic biological investigations, free radical scavenging, anticancer activities, and DNA cleavage studies, were carried out for the complexes. Antioxidant studies showed that the complexes have significant antioxidant activity against DPPH, hydroxyl, nitric oxide radicals and hydrogen peroxide assay. The in vitro cytotoxicity of complexes against breast cancer (MCF-7) cell line was assayed showing high cytotoxicity with low IC₅₀ values indicating their efficiency in destroying the cancer cells even at very low concentrations. The DNA cleavage studies showed that the complexes efficiently cleaved DNA.     

Copper(II) complexes of acylhydrazones: synthesis,characterization and DNA interaction

Two new acylhydrazone copper(II) complexes of 4‐hydroxy‐N′‐[(1E)‐1‐(4‐methylphenyl)ethylidene]benzohydrazide (HL¹) and 4 ethyl [4‐({(2E)‐2‐[1‐(4‐methylphenyl)ethylidene]hydrazinyl}carbonyl)phenoxy]acetate (HL²) have been synthesized and characterized. The structures of both acylhydrazone and copper(II) complexes were identified by elemental analysis, infrared spectra, UV–visible electronic absorption spectra, magnetic susceptibility measurements, TGA and powder X‐ray diffraction. DNA binding and DNA cleavage activities of the synthesized copper complexes were examined by using UV‐visible titration and agarose gel electrophoresis, respectively. The effect of complex concentration on the DNA cleavage reactions in the absence and presence of H₂O₂ was also investigated. The results indicate that all the complexes bind slightly to calf thymus DNA and cleavage pBR322 DNA. The mechanistic studies demonstrate that a hydrogen peroxide‐derived species and singlet oxygen (¹O₂) are the active oxidative species for DNA cleavage. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis of unsymmetrical compartmental oxime nickel(II) and copper(II) complexes: spectral, electrochemical and magnetic studies

A new series of binuclear unsymmetrical compartmental oxime complexes (1–5) [M₂L] [M=Cu(II), Ni(II)] have been synthesized using mononuclear complex [ML] (L=1,4-bis[2-hydroxy-3-(formyl)-5-methylbenzyl]piperazine), hydroxylamine hydrochloride and triethylamine. In this system there are two different compartments, one has piperazinyl nitrogens and phenolic oxygens and the other compartment has two oxime nitrogens and phenolic oxygens as coordinating sites. The complexes were characterized by elemental and spectral analysis. Electrochemical studies of the complexes show two step single electron quasi-reversible redox processes at cathodic potential region. For copper complexes E¹ _pc=−0.18 to −0.62 and E² _pc=−1.18 to −1.25 V, for nickel complexes E¹ _pc=−0.40 to −0.63 and E² _pc=−1.08 to −1.10 V and reduction potentials are sensitive towards the chemical environment around the copper and nickel atoms. The nickel(II) complexes undergo two electrons oxidation. The first one electron oxidation is observed around +0.75 V and the second around +1.13 V. ESR Spectra of the binuclear copper(II) complexes [Cu₂L](ClO₄), [Cu₂L(Cl)], [Cu₂L(NO₃)] shows a broad signal at g=2.1 indicating the presence of coupling between the two copper centers. Copper(II) complexes show a magnetic moment value of μ_eff around 1.59 B.M at 298 K and variable temperature magnetic measurements show a −2J value of 172 cm⁻¹ indicating presence of antiferromagnetic exchange interaction between copper(II) centres.     

Hydrolytic cleavage of DNA by quercetin manganese(II) complexes

Quercetin manganese(II) complexes were investigated focusing on its DNA hydrolytic activity. The complexes successfully promote the cleavage of plasmid DNA, producing single and double DNA strand breaks. The amount of conversion of supercoiled form (SC) of plasmid DNA to the nicked circular form (NC) depends on the concentration of the complex as well as the duration of incubation of the complexes with DNA. The maximum rate of conversion of the supercoiled form to the nicked circular form at pH 7.2 in the presence of 100 μM of the complexes is found to be 1.32 × 10⁻⁴ s⁻¹. The hydrolytic cleavage of DNA by the complexes was supported by the evidence from free radical quenching, thiobarbituric acid-reactive substances (TBARS) assay and T4 ligase ligation.     

Synthesis,characterization, antimicrobial,DNA binding,and oxidative cleavage activities of Cu(II) and Co(II) complexes with 2-(2-hydroxybenzylideneamino)isoindoline-1,3-dione

(E)-2-(2-hydroxybenzylideneamino)isoindoline-1,3-dione (Hbid) was prepared by condensation of N-aminophthalimide and salicylaldehyde and characterized by elemental analysis, IR, ¹H-NMR, and mass spectral studies. Mononuclear complexes [(phen)Cu^II(μ-Hbid)₂H₂O] (1), [(phen)Co^II(Cl)₂(μ-Hbid)]6H₂O (2) (phen?=?1,10-phenanthroline) and binuclear complexes [Cu^II(μ-Hbid)]₂ (3), and [Co^II(μ-Hbid)]₂ (4) with Hbid were prepared and characterized by elemental analysis, IR, UV-Vis, molar conductance, and thermogravimetric (TG) techniques. DNA-binding properties of 1–4 were investigated by UV spectroscopy, fluorescence spectroscopy, and viscosity measurements. The results suggest that 1 and 2 bind to DNA by partial intercalation, whereas 3 and 4 find different groove-binding sites. The cleavage of these complexes with super coiled pUC19 has been studied using gel electrophoresis; all the complexes displayed chemical nuclease activity in the absence and presence of H₂O₂ via an oxidative mechanism. Complexes 1–4 inhibit the growth of both Gram-positive and Gram-negative bacteria.     

Effect of 1,10-phenanthroline on DNA binding,DNA cleavage,cytotoxic and lactate dehydrogenase inhibition properties of Robson type macrocyclic dicopper(II) complex

DNA targeting macrocyclic dicopper(II) complex, [Cu₂L(H₂O)₂](phen)₂(ClO₄)₂ (L = μ-11,23-dimethyl-3,7,15,19-tetraazatricyclo-[19.3.1.1^9,13,21] he p t a c o s a-1(24), 2, 7, 9, 11, 13(26), 14, 19, 21(25), 22-decaene-25,26-diol) (2), has been synthesized and characterized. This has been synthesized by reacting a Robson type macrocyclic precursor dicopper(II) complex [Cu₂L(H₂O)₂](ClO₄)₂ (1) and 1,10-phenanthroline in ethanol. Solution ESR, electronic, and ESI-MS spectral studies suggest that 1,10-phenanthroline replaces coordinated water in 1, giving 2. The influence of the phenanthroline on DNA binding, cleavage, and anticancer properties of 2 have been investigated. Complex 2 displays better DNA binding and cleavage than 1. The dicopper(II) complexes 1 and 2 show cytotoxicity in human cervical HeLa cancer cells, giving IC₅₀ values of 79.41 and 15.82 μM, respectively. Antiproliferative properties of 1 and 2 were confirmed by Trypan Blue exclusive assay and lactate dehydrogenase enzyme level in HeLa cancer cell lysate and content media.     

Phosphoester binding,DNA binding,DNA cleavage and in vitro cytotoxicity studies of simple heteroleptic copper(II) complexes with bidentate ligands

Abstract

Two mononuclear heteroleptic copper complexes, [Cu(±trans-dach)(bpy)](ClO₄)₂ 1a and [Cu(±trans-dach)(phen)](ClO₄)₂ 2a [dach?=?1,2-diaminocyclohexane, bpy?=?2,2′-bipyridine and phen?=?1,10-phenanthroline], were synthesized and analyzed by CHN analysis, electronic absorption, FT-IR spectroscopy, EPR, and SXRD. The molecular structures of 1a and 2a showed octahedral geometry around Cu(II). Both complexes interacted with phosphoesters and DNA. Their binding affinities with diphenylphosphate, di n-butylphosphate, trimethylphosphate, and triphenylphosphate were studied by UV–vis spectroscopy. For understanding the stereochemical role of dach ligand toward DNA interaction, enantiopure DACH complexes [Cu(R,R-trans-dach(bpy)](ClO₄)₂ 1b, [Cu(S,S-trans-dach)(bpy)](ClO₄)₂ 1c, [Cu(cis-dach)(bpy)](ClO₄)₂ 1d, [Cu(R,R-trans-dach)(phen)](ClO₄)₂ 2b, [Cu(S,S-trans-dach)(phen)](ClO₄)₂ 2c, and [Cu(cis-dach)(phen)](ClO₄)₂ 2d were synthesized and analyzed. All complexes interacted with calf thymus-DNA (CT-DNA) as studied by UV–vis spectroscopy. The nature of binding to CT-DNA was groove/electrostatic as supported by circular dichroism, cyclic voltammetry, and docking studies. Complexes were able to cleave plasmid DNA at 12.5 µM (1a–d) and 6 µM (2a–d), where 2d showed 64% Form II and 36% Form III. The in vitro cytotoxic studies of two different cancer cell lines showed inhibition with low IC₅₀ value in comparison to reference control (cisplatin). These complexes are efficient in inducing apoptosis in cancer cells, making them viable for potent anticancer activity.