Nano-sized Cu(II) and Zn(II) complexes and their use as a precursor for synthesis of CuO and ZnO nanoparticles: A study on their sonochemical synthesis,characterization, and DNA-binding/cleavage,anticancer, and antimicrobial activities

Two new divalent copper (C1) and zinc (C2) chelates having the formulae [M(PIMC)₂] (where M = Cu(II), Zn(II) and PIMC = Ligand [(E)-3-(((3-hydroxypyridin-2-yl)imino)methyl)-4H-chromen-4-one] were obtained and characterized by several techniques. Structures and geometries of the synthesized complexes were judged based on the results of alternative analytical and spectral tools supporting the proposed formulae. IR spectral data confirmed the coordination of the ligands to the copper and zinc centers as monobasic tridentate in the enol form. Thermal analysis, UV-Vis spectra and magnetic moment confirmed the geometry around the copper center to be tetrahedral, square pyramidal and octahedral. Study of the binding ability of the synthesized compounds with Circulating tumor DNA (CT-DNA) bas been evaluated applying UV-Vis spectral titration and viscosity measurements. The copper and zinc oxides were achieved from the copper and zinc nano-particles structures Schiff base complexes as the raw material after calcination for 5 hr at 600°C. On the other hand, synthesized of C1 and C2 NPs were used as suitable precursors to the preparation of CuO and ZnO NPs. Finally, the synthesized of the two complexes exhibited enhanced activity against the tested bacterial (Staphylococcus aureus and Escherichia Coli) and fungal strains (Candida albicans and Aspergillus fumigatus) as compared to HPIMC. Among all these synthesized compounds, C1 exhibits good cleaving ability compared to other newly synthesized C2.     

Synthesis and characterization of heteroleptic Schiff base transition metal complexes: a study of anticancer,antimicrobial, DNA cleavage and anti-TB activity

In search of effective bioactive compounds, we have synthesized the new Co(II), Ni(II), and Cu(II) complexes of the Schiff base derived from 8-formyl-7-hydroxy-4-methylcoumarin and 2-hydrazino benzothiazole and characterized by analytical, spectroscopic (IR, NMR, UV–vis, Mass), magnetic, powder X-ray diffraction data (PXRD) and TGA studies. Elemental analysis suggests the stoichiometry of the synthesized complexes and the solution electronic spectral study revealed the octahedral geometry of the compounds. Thermal analysis shows the presence of water molecule outside the coordination sphere and powder-XRD patterns have been studied to test the degree of crystallinity of the complexes and unit cell calculations were made. All the synthesized compounds were tested against human ovarian cancer cell line (PA-1). The synthesized metal complexes exhibited enhanced activity against the tested bacterial (Staphylococcus aureus and Escherichia Coli) and fungal strains (Candida albicans and Aspergillus fumigatus) as compared to free ligand (LH). The results of the DNA-cleavage activity suggest that the ligand and its metal complexes can cleave CT-DNA at different degrees. Further, anti-tuberculosis activity was done using microplate almar blue assay. Among all these synthesized compounds, the Cu(II) complex exhibits good cleaving ability compared to other newly synthesized metal complexes.     

DNA cleavage activities of tetraazamacrocyclic oxamido nickel(II) complexes

The DNA cleavage activities of nickel(II) ion and four closely related macrocyclic nickel(II) complexes NiL¹ ∼ NiL⁴ in the absence of any added redox cofactors are compared and the structure of NiL³ methanol solvate has been characterized by single crystal X-ray analysis, where L¹ ∼ L⁴ are the dianions of tetraazamacrocyclic oxamido Schiff bases. In NiL³·MeOH, the macrocyclic [N₄] ligand coordinates to the central Ni(II) ion forming a distorted square–planar geometry. The adjacent mononuclear molecules are linked by O–H?O hydrogen bonds and Ni?O and Ni?L van der Waals forces into 2D supramolecular structure. Agarose gel electrophoresis studies indicate that the ability of these nickel(II) complexes to cleave DNA is highly dependent upon the ligand employed. In the absence of any added oxidizing agents, only NiL³ is a relatively good DNA cleavage agent, and the process of plasmid DNA cleavage is much sensitive to ionic strength and pH value. The NiL³-mediated DNA cleavage reaction is a typical pseudo-first-order consecutive reaction, and the rate constants of 0.148 ± 0.007 h⁻¹ (k₁) and 0.0118 ± 0.0018 h⁻¹ (k₂) for the conversion of supercoiled to nicked DNA and nicked to linear DNA are obtained in presence of 0.5 mmol L⁻¹ NiL³. The results of DNA cleavage experiments, combining with those of circular dichroism (CD) and fluorescence spectroscopy indicate that the main binding modes between DNA and the complexes should be groove binding and electrostatic interaction.     

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,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.     

1,3-Bis(2-alkyltetrazol-5-yl)triazenes and their Fe(II), Co(II) and Ni(II) complexes: Synthesis,spectroscopy, and thermal properties. Crystal structure of Fe(II) and Co(II) 1,3-bis(2-methyltetrazol-5-yl)triazenide complexes

Complexes ML¹₂ and ML²₂, with M = Fe^II, Co^II, Ni^II, and 1,3-bis(2-R-tetrazol-5-yl)triazenide ligands L¹ (R = Me) and L² (R = ^tBu), have been synthesized by the reaction of corresponding 1,3-bis(2-R-tetrazol-5-yl)triazenes with metal(II) salts in basic media and characterized by IR, UV–Vis spectroscopy, thermal and X-ray diffraction analyses. Both 1,3-bis(2-R-tetrazol-5-yl)triazenes were found to deprotonate on coordination and act as tridentate chelating ligands forming distorted MN₆ octahedra around metal(II) cations.     

Synthesis,crystal structures,DNA binding and cleavage properties and protein binding activities of three mononuclear cobalt(II) complexes

Three new mononuclear cobalt(II) complexes containing ligands with extended planar quinoxaline moieties, {dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz) or dipyrido[3,2‐d:2′,3′‐f]quinoxaline (dpq)}, viz. [Co(dppz)(acac)₂] · CH₃OH ( 1 ), [Co(dpq)(tfnb)₂] ( 2 ) and [Co(dpq)(dbm)₂] ( 3 ), where acac = acetylacetonate, tfnb = benzoyltrifluoroacetone and dbm = dibenzoylmethane, have been synthesized and structurally characterized as octahedral complexes. The binding ability of the complexes with calf thymus (CT)‐DNA has been investigated by spectroscopic and viscosity measurements. Results indicate that all complexes bind to CT‐DNA via intercalative mode, and the DNA binding affinity of dppz complex 1 is apparently stronger than that of dpq complexes 2 and 3 . Furthermore, DNA photocleavage experiments indicate that these complexes are efficient DNA cleaving agents in UV‐A (365 nm) and hydroxyl radical (HO^·), singlet oxygen (¹O₂) and superoxide anion (¹O₂^?) serve as the major cleavage active species. In addition, interaction of the complexes with bovine serum albumin (BSA) was investigated using UV ? visible and fluorescence methods, which indicated that all complexes could quench the intrinsic fluorescence of BSA in a static quenching process. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthesis,characterization, and DNA binding of two copper(II) complexes as DNA fluorescent probes

[Cu(DAPT)₂Cl]Cl·H₂O and [Cu(DBM)(DAPT)Cl] [DAPT = 2,4-diamine-6-(pyrazin-2-yl)-1,3,5-triazine] were synthesized and characterized by IR and UV spectroscopy, elemental analysis, TG–DTA, molar conductivity, and LC–MS. The interaction with calf thymus DNA (ct-DNA) of the two complexes has been studied using UV spectra, fluorescent spectra, cyclic voltammetry, and viscosity measurements. The complexes interact with ct-DNA through classical intercalation. Fluorescence intensity changes of 1 and 2 in the absence and presence of ct-DNA have been investigated for quantitative determination of ct-DNA with the limit of detection of 3.8 and 7.7 ng mL^?1, respectively. From the result, the two complexes are potentially sensitive DNA fluorescent probes.     

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.     

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 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.     

DNA binding and cleavage behaviors of copper(II) complexes with amidino-O-methylurea and N-methylphenyl-amidino-O-methylurea,and their antibacterial activities

The two designed copper(II) complexes, [Cu(L^1m)₂]Cl₂ (1) (L^1m = amidino-O-methylurea) and [Cu(L^2m)₂]Cl₂ (2) (L^2m = N-methylphenyl-amidino-O-methylurea), have been investigated for their interaction with calf thymus DNA by utilizing the absorption titration method, viscometric studies and thermal denaturation. The cleavage reaction on pBR322 DNA has been monitored by agarose gel electrophoresis. The results suggest that the two complexes can bind to DNA by non-intercalative modes and exhibit nuclease activities in which supercoiled plasmid DNA is converted to the linear form. Complex 2, with an intrinsic binding constant (K_b) of 1.16 × 10⁵ M⁻¹, shows a higher binding efficiency and a better nuclease activity than complex 1, with a K_b value of 5.67 × 10⁴ M⁻¹. Their DNA cleavage potential can be significantly enhanced by hydrogen peroxide, indicating an oxidative cleavage process. Further examination of the antibacterial activities against Campylobacter has revealed inhibition zones of 9.0 (for 1) and 14.5 mm (for 2), which are in agreement with their minimum inhibitory concentration (MIC) values of 1.56 and 0.78 mg mL⁻¹, respectively. The substantially better reactivity of 2 results from the aromatic moieties on the side chain of the L^2m ligand which act as an additional binding site.     

Synthesis,crystal structures,DNA/bovine serum albumin binding,DNA cleavage and cytotoxicity of five mononuclear zinc(II) complexes

Five new mononuclear zinc(II) complexes containing ligands with extended planar phenanthroline moieties (dipyrido‐[3,2‐a:2′,3′‐c]phenazine (dppz) or dipyrido[3,2‐d:2′,3′‐f] quinoxaline (dpq)), namely [Zn(dppz)(acac)₂]⋅CH₃OH ( 1 ), [Zn(dppz)(dbm)(OAc)] ( 2 ), [Zn(dpq)(dbm) (OAc)] 1.5H₂O ( 3 ), [Zn(dpq)(tfnb)(OAc)] ( 4 ) and [Zn(dpq)(tfnb)₂] ( 5 ), where acac = acetylacetonate, tfnb = benzoyltrifluoroacetone and dbm = dibenzoylmethane, were synthesized and structurally characterized. The binding ability of complexes 1 – 5 with calf thymus DNA was investigated by spectroscopic titration methods and viscosity measurements. Results indicate that all complexes bind to calf thymus DNA via intercalative mode, and the DNA binding affinities of dppz complexes 1 and 2 are apparently stronger than those of dpq complexes 3 – 5 . DNA photocleavage experiments reveal that these complexes are efficient DNA cleaving agents and they are more active in UV‐A (365 nm) than in visible light. In particular, the in vitro cytotoxicity of the complexes for human cancer cell line A549 demonstrates that the five compounds have anticancer activity with low IC₅₀ values. Meanwhile, interaction of the complexes with bovine serum albumin investigated using UV–visible and fluorescence methods indicates that all complexes can quench the intrinsic fluorescence of bovine serum albumin in a static quenching process.     

Syntheses, X-ray crystal structures, DNA binding, oxidative cleavage activities and antimicrobial studies of two Cu(II) hydrazone complexes

From a mononuclear Cu(II)-hydrazone complex [Cu(PBH)₂] (1), one μ_1,1-azido bridged dinuclear Cu(II) complex having the formula [{Cu(PBH)(μ_1,1-NNN)}₂] (2) (where HPBH = 2-pyridinecarboxaldehyde benzoyl hydrazone) has been synthesised. Both the complexes are characterised by elemental analyses, IR and UV–Vis spectroscopic studies. The tridentate hydrazone pro-ligand (HPBH) is obtained by the condensation of benzhydrazide and pyridine-2-carboxaldehyde. The structures of the complexes have conclusively been established by the X-ray single crystal diffraction method. Complex 1 and 2 both display DNA binding ability, which is ascertained by UV–Vis titration and cyclic voltammetric studies using calf thymus DNA (CT-DNA). The apparent binding constants (K_app) are of moderate values and are 2.048 × 10⁴ M⁻¹ (±0.006) and 1.644 × 10⁴ M⁻¹ (±0.005), respectively. The modes of binding of the complexes with CT-DNA has been investigated using circular dichroism, ethidium bromide displacement assay and viscosity measurements. The cleavage properties of these complexes as well as the free pro-ligand with super coiled (SC) pUC19 are studied using the gel electrophoresis method, where both the complexes displayed chemical nuclease activity in the presence of H₂O₂ via an oxidative mechanism. The antimicrobial study using the free pro-ligand, 1 and 2 against both Gram positive and Gram negative bacteria are performed, 2 showed antimicrobial activity against both Gram negative and Gram positive bacteria whereas the free ligand and 1 show no antibacterial activity.     

Synthesis,crystal structure,DNA binding,and oxidative cleavage activity of copper(II)-bipyridyl complexes containing tetraalkylammonium groups

Two copper(II) complexes of disubstituted 2,2′-bipyridine (bpy = 2, 2′-bipyridine) with tetraalkylammonium groups, [Cu(L¹)₂Br](ClO₄)₅·2H₂O (1) and [Cu(L²)₂Br](ClO₄)₅·H₂O (2) (L¹ = [4, 4′-(Et₃NCH₂)₂-bpy]²⁺, L² = [4, 4′-((n-Bu)₃NCH₂)₂-bpy]²⁺), have been synthesized and characterized. X-ray crystallographic study of 1 indicates that Cu(II) is a distorted trigonal bipyramidal or square pyramid. DNA binding of both complexes was studied by UV spectroscopic titration. In the presence of reducing reagents, the cleavage of plasmid pBR322 DNA mediated by both complexes was investigated and efficient oxidative cleavage of DNA was observed. Mechanistic study with reactive oxygen scavengers indicates that hydrogen peroxide and singlet oxygen participate in DNA cleavage.     

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 anticancer zinc(II) complexes comprising thiosemicarbazones of saturated ring: structure,DNA/protein binding,DNA cleavage,topoisomerase‐1 inhibition and anti‐proliferation studies

The reaction of the thiosemicarbazones (CH₂)₄C?NN(H)C(?S)NHR (R = H, Me) with zinc(II) acetate in methanolic solution proceeds readily under mild conditions to form stable mononuclear complexes Zn[(CH₂)₄C?NN?C(S)NHR]₂. DNA interaction studies show that the zinc(II) complexes bind to DNA via groove mode and exhibit efficient DNA cleavage activity in the presence of hydrogen peroxide. Also, the complexes display a binding affinity to bovine serum albumin protein with K_BSA values of ca 10⁵ M^?1. Topoisomerase catalytic inhibition studies suggest that both complexes are efficient topoisomerase‐I impeders. Furthermore, the anti‐proliferative effects of the two complexes on five human tumor cell lines (Caki‐2, MCF‐7, CaSki, NCI‐H322M and Co‐115) indicate that both complexes have the potential to act as effective anticancer drugs. Copyright © 2016 John Wiley & Sons, Ltd.     

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.