Synthesis,spectroscopic, thermal and biological aspects of drug‐based copper(II) complexes

A series of novel complexes of the type Cu(II)(L_n)₂(H₂O)₂]^•xH₂O [where L_n = L _1–4 , these ligands being described as: L ₁ , 2‐({4‐[6,7‐dihydrothieno[3,2‐c]pyridin‐5(4H)‐ylsulfonyl]phenylimino}methyl)phenol, x = 1; L ₂ , 2‐({4‐[6,7‐dihydrothieno[3,2‐c] pyridin‐5(4H)‐ylsulfonyl]phenylimino}methyl)‐5‐(methoxy)phenol, x = 2; L ₃ , 5‐chloro‐2‐({4‐[6,7‐dihydrothieno[3,2‐c]pyridin‐5(4H)‐ylsulfonyl]phenylimino}methyl)phenol, x = 2; and L ₄ , 5‐bromo‐4‐chloro‐2‐({4‐[6,7‐dihydrothieno[3,2‐c]pyridin‐5(4H)‐ylsulfonyl]phenylimino} methyl)phenol, x = 1] was investigated. They were characterized by elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR and electronic spectra, magnetic measurements and thermal studies. The FAB‐mass spectrum of [Cu(II)( L ₁ )₂(H₂O)₂]^•H₂O was determined. A magnetic moment and reflectance spectral study revealed that an octahedral geometry could be assigned to all the prepared complexes. Ligands (L_n) and their metal complexes were screened for their in vitro antibacterial activity against Bacillus subtillis, Pseudomonas aeruginosa, Escherichia coli and Serratia marcescens bacterial strains. Kinetic parameters such as order of reaction (n), the energy of activation (E_a), the pre‐exponential factor (A), the activation entropy (ΔS^≠), the activation enthalpy (ΔH^≠) and the free energy of activation (ΔG^≠) are reported. Copyright © 2011 John Wiley & Sons, Ltd.     

Synthesis,spectral investigation and development of tetrahedral copper(II) complexes as artificial metallonucleases and antimalarial agents

Seven new copper(II) complexes of type [Cu(A)(L)]?H₂O (A = sparfloxacin, ciprofloxacin, levofloxacin, gatifloxacin, pefloxacin, ofloxacin, norfloxacin; L = 5‐[(3‐chlorophenyl)diazenyl]‐4‐hydroxy‐1,3‐thiazole‐2(3H)‐thione) were synthesized and characterized using elemental and thermogravimetric analyses, and electronic, electron paramagnetic resonance (EPR), Fourier transform infrared and liquid chromatography–mass spectroscopies. Tetrahedral geometry around copper is assigned in all complexes using EPR and electronic spectral analyses. All complexes were investigated for their interaction with herring sperm DNA utilizing absorption titration (K_b = 1.27–3.13 × 10⁵ M^?1) and hydrodynamic volume measurement studies. The studies suggest the classical intercalative mode of DNA binding. The cleavage reaction on pUC19 DNA was monitored by agarose gel electrophoresis. The results indicate that the Cu(II) complexes can more effectively promote the cleavage of plasmid DNA. The superoxide dismutase mimic activity of the complexes was evaluated by nitroblue tetrazolium assay, and the complexes catalysed the dismutation of superoxide at pH = 7.8 with IC₅₀ values in the range 0.597–0.900 μM. The complexes were screened for their in vitro antibacterial activity against five pathogenic bacteria. All the complexes are good cytotoxic agents and show LC₅₀ values ranging from 5.559 to 11.912 µg ml^?1. All newly synthesized Cu(II) complexes were also evaluated for their in vitro antimalarial activity against Plasmodium falciparum strain (IC₅₀ = 0.62–2.0 µg ml^?1). Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis,interaction with double-helical DNA and biological activity of new Pt(II) and Pd(II) complexes with phenylglycine

The mononuclear palladium(II) (1) and platinum(II) (2) complexes containing phenylglycine have been synthesized and characterized by elemental analysis, IR spectra, and ¹H NMR spectra. The structure of 1 was determined by X-ray diffractometry. The interaction between the complexes and fish sperm DNA (FS-DNA), adenosine-5′-triphosphate (ATP), and adenine (Ade) were investigated by UV absorption spectra, the interaction mode of the complex binding to DNA was studied by fluorescence spectra and viscometry. The results indicate that the two complexes have different binding affinities to DNA, complex 2 > complex 1. Gel electrophoresis assay demonstrates that the two complexes have the ability to cleave pBR322 plasmid DNA. Cytotoxicity experiments were carried out toward four different cancer cell lines, and 1 shows lower inhibitory efficiency than 2, consistent with the binding affinities towards DNA.     

DNA interaction,free radical scavenging and in‐vitro antibacterial activity of drug‐based copper(II) complexes

The Cu(II) complexes of type [Cu(cpf)(Aⁿ)Cl] (Aⁿ = terpyridines, cpf = ciprofloxacin) were synthesized and characterized using IR, mass and reflectance spectra. The free ligands and their complexes were evaluated for their in‐vitro antimicrobial activity against a panel of Gram‐positive and Gram‐negative bacteria. The complexes exhibit better or equal inhibition in comparison to free fluoroquinolones. Binding interactions of the complexes with calf thymus (CT DNA) were investigated by absorption titration, viscosity studies and DNA melting temperature experiment. The cleavage reaction on pUC19 DNA was monitored by agarose gel electrophoresis. The lower concentration of the complexes was catalysed the dismutation of superoxide radical at biological pH, which indicates that the complexes can act as a possible model for superoxide dismutase. Copyright © 2011 John Wiley & Sons, Ltd.     

Synthesis,DNA binding,nuclease activity and cytotoxic studies of a wheel‐shaped octanuclear copper(II) complex based on 1,2,4‐triazole

The antitumor activity shown by many platinum complexes has produced a strong interest in research of new organometallic compounds. Among the metal compounds synthesized and tested, copper compounds have received considerable attention because of their cytotoxic activity against solid tumors. A novel wheel‐shaped octanuclear copper(II) complex with a 1,2,4‐triazole derivative ligand formulated as [Cu₈L₄](ClO₄)₈?11H₂O ( 1 ) (L = 3,5‐bis((bis(2‐hydroxylethyl)amino)methyl)‐4 H‐1,2,4,‐triazole‐4‐amine) has been synthesized and structurally characterized. In 1 , eight Cu atoms are linked through 1,2,4‐triazole units and alkoxide bridges to form a centrosymmetric octanuclear Cu(II) metallomacrocycle. The interaction of complex 1 with calf thymus DNA has been studied using UV absorption, fluorescence and circular dichroism spectroscopies, viscosity measurements and cyclic voltammetry. The apparent binding constant (k_app) value for 1 is 1.59 × 10⁵ M^?1. Furthermore, complex 1 displays efficient oxidative cleavage of supercoiled DNA in the presence of external agents, the rate constant for the conversion of supercoiled to nicked DNA being 2.67 × 10^?5 s^?1. Interestingly, cytotoxicity studies on the MCF‐7 human breast cancer cell line show that the IC₅₀ value of 1 is less than that of cisplatin for the same cell line, revealing that it has the potential to act as an effective metal‐based anticancer drug. Copyright © 2016 John Wiley & Sons, Ltd.     

Heteroscorpionate‐based heteroleptic copper(II) complexes: Antioxidant,molecular docking and in vitro cytotoxicity studies

Three new heteroscorpionate ligands, (2‐hydroxyphenyl)bis(imidazol‐1‐yl)methane (HL¹), (4‐diethylamino‐2‐hydroxyphenyl)bis(imidazol‐1‐yl)methane (HL²) and (5‐bromo‐2‐hydroxyphenyl)bis(imidazol‐1‐yl)methane (HL³), and their heteroleptic copper(II) complexes of the type [Cu(L^1–3)diimine]ClO₄ ( 1 – 6 ; where diimine =2,2′‐bipyridyl or 1,10‐phenanthroline) have been synthesized and characterized using spectroscopic methods. The molecular structure of ligand HL¹ was determined by single‐crystal X‐ray diffraction. UV–visible, electron paramagnetic resonance and theoretical studies suggest a distorted square pyramidal geometry around copper(II) ion. Analyses of highest occupied and lowest unoccupied molecular orbitals have been used to explain the charge transfer taking place within the complexes. The antioxidant activities of the heteroscorpionate ligands and their heteroleptic copper(II) complexes were determined using ABTS, DPPH and H₂O₂ free radical scavenging assays with respect to standard antioxidant ascorbic acid. In molecular docking studies, the complexes showed π–π, hydrogen bonding, van der Waals and electrostatic interactions with fibroblast growth factor receptor kinase. In vitro cytotoxicity activities of ligands and copper(II) complexes were examined on human breast adenocarcinoma (MCF‐7), cervical (HeLa) and lung (A549) cancer cell lines and normal human dermal fibroblast cell line using MTT assay. Complex 4 exhibited higher anticancer activity than the other complexes against all three cancer lines, being more potent than the standard drug cisplatin.     

Synthesis,crystal structure and biological properties of a cis‐dichloridobis(diimine)copper(II) complex

The mechanisms of interaction of inorganic complexes with DNA are important in the design and development of new metal‐based drug molecules. The limitations of cis‐platin have encouraged the design and development of new metal‐based target‐specific anticancer drugs having reduced side effects. The complex cis‐dichloridobis(1,2,5‐thiadiazolo[3,4‐f][1,10]phenanthroline‐κ²N¹,N¹⁰)copper(II), [CuCl₂(C₁₂H₆N₄S)₂], has been synthesized and characterized. The complex crystallizes in the monoclinic space group C2/c. The covalent binding of the complex with DNA was studied by absorption spectroscopy. The anticancer activity of the complex on the Human Lung Carcinoma (A549) cell line was investigated by MTT assay. The complex exhibits higher toxicity than cis‐platin and induces an apoptotic mode of cell death.     

司帕沙星及均三嗪衍生物铜(II)配合物与DNA作用及其抗肿瘤活性

DNA是抗肿瘤药物的重要靶点,研究药物分子与DNA之间的作用有助于设计靶向DNA类抗肿瘤药物.合成和表征了新的三元铜（II）配合物[Cu（Sf）（PyTA）（H₂O）]·ClO₄·3.5H₂O[Sf=司帕沙星,5-氨基-1-环丙基-7-（顺-3,5-二甲基-1-哌嗪基）-6,8-二氟-1,4-二氢-4-氧-3-喹啉羧酸、PyTA=2,4-二氨基-6-（2'-吡啶基）-1,3,5-均三嗪].利用电子吸收光谱、KI荧光猝灭光谱、粘度测定以及分子对接技术研究了配合物与DNA之间作用,发现配合物以插入模式与DNA结合,结合常数K_b=1.23×10⁴ L/mol.此外,应用MTT[3-（4,5-二甲基噻唑-2）-2,5-二苯基四氮唑溴盐]比色法检测了配合物的细胞毒性作用,发现配合物对癌细胞A549、Bel-7402和Eca-109等表现出良好的抑制作用[IC₅₀=（57.0±1.6）~（77.6±1.4）μmol/L].尤为重要的是,通过单细胞凝胶电泳、Hoechst 33342染色、Annexin V-FITC/PI双染流式细胞术、测定线粒体膜电位、检测细胞色素C和胞内Ca²⁺水平及细胞周期分析探究了配合物抗肿瘤作用机制,结果表明,配合物通过DNA结合及线粒体功能障碍途径诱导细胞凋亡,使细胞S和G2/M周期发生阻滞并造成DNA损伤.     

Equilibrium studies of beta-diketoaryl azo compounds with cobalt(II), nickel(II) and copper(II)

The interactions of some beta-diketoaryl azo substituted compounds with Co(II), Ni(II) and Cu(II) are discussed. The non-protonated form of the ligand is the main complexing species. The stability constants have been evaluated. The effect of substituent groups on the complexing ability of the ligands is discussed.     

Pulse and steady‐state radiolysis studies of some homonuclear copper(II) and heteronuclear copper(II)‐molybdenum(VI) peroxo compounds containing a simple peptide molecule

The reactions of e_aq⁻, OH·, CO₂⁻·, and N₃· radicals with some novel homo nuclear and hetero nuclear peroxo peptide complexes viz: copper peroxo glycylglycine, [Cu(O₂)(H₂L)₂]; molybdenum oxoperoxo glycylglycine, [Mo(O)(O₂)₂(H₂L)₂]; Cu,Mo oxoperoxo glycylglycine [CuMo(O)(O₂)(L)₂] and Cu,Mo, oxo glycylglycine, [CuMo(O)₂(L)₂] (H₂L=glycyl glycine) in aqueous solutions were investigated by pulse radiolysis. Three types of reactions were observed: (1) reduction of Cu(II) to Cu(I) by e_aq⁻ and CO₂⁻·, (2) oxidation of Cu(II) to Cu(III) by N₃⁻·, and (3) formation of a radical on H abstraction from the ligand by OH· radical. Rate constants were reported for formation and decomposition of all intermediates. In case of one electron reduced complexes of hetero atoms, CuMo(O)₂L₂ and CuMo(O)(O₂)L₂, prepared via the reduction of the corresponding complexes by e_aq⁻, formation of a new dimer radical anion complex was observed. It is also noteworthy to mention the possibility of the effect of peroxo ligand on intermediate steps during the formation of Cu clusters. © 1999 John Wiley & Sons, Inc. Int J Chem Kinet 31: 159–168, 1999     

Intercalation of molybdenum disulfide with chlorobis(phenanthroline)copper(II)

An intercalation compound of molybdenum disulfide with the copper complex Cu^II(phen)₂Cl⁺ was found to form by the interaction of the MoS₂ single-layer dispersions with the complex and by the treatment of the phenanthroline intercalation compound with CuCl₂. The compositions and structures of the compounds formed were determined by powder diffractometry and electron microscopy. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2648–2654, December, 2005.     

Co(II), Mn(II) and Cu(II) complexes of fluoroquinolones: Synthesis, spectroscopical studies and biological evaluation against Trypanosoma cruzi

[MnCl₂(NOR)(H₂O)₂] (1), [MnCl₂(SPAR)(H₂O)₂] (2), [CoCl₂(NOR)(H₂O)₂] (3) [CoCl₂(SPAR)(H₂O)₂] (4), [CuCl₂(phen)(NOR)] (5) and [CuCl₂(phen)(SPAR)] (6) complexes with norfloxacin (NOR) and sparfloxacin (SPAR) were obtained from MnCl₂·4H₂O, CoCl₂·4H₂O and CuCl₂(phen). In all cases the NOR and SPAR coordinate in the neutral zwitterionic form. The electron paramagnetic resonance spectra of the Cu(II) complexes (5) and (6) in aqueous and DMSO solutions indicate mixture of mononuclear and binuclear complex. Complexes (1-6), together with the corresponding ligands were evaluated for their in vitro trypanocidal effect, against both bloodstream trypomastigotes and intracellular forms of Trypanosoma cruzi. SPAR and NOR were poorly effective upon T. cruzi, complexes (3) and (4) were active against intracellular forms of the parasite. The complexes (5) and (6) displayed a higher activity upon both bloodstream and intracellular forms. The potency of fluoroquinolones, specially those coordinated to Cu(II)-phen justify further trypanocidal screening assays with this compounds in vitro as well as upon experimental models of T. cruzi infection.     

DNA‐binding,antibacterial and spectral investigations of drug–Fe(II) complexes

The antibiotic agent ciprofloxacin is well known for its drug design and coordinating ability towards metal ions. Iron(II) complexes of ciprofloxacin with various neutral bidentate ligands have been prepared. The structure of complexes has been investigated using spectral, physicochemical and elemental analyses. Antibacterial activity has been carried out using agar plate technique against Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Salmonella typhi, Escherichia coli and Serratia marcescens. The results show a significant increase in antibacterial activity compared with parental ligands, metal salt and standard drugs (ofloxacin, levofloxacin). The DNA binding and cleavage efficacy were determined using absorption titration and gel electrophoresis techniques, respectively. The DNA binding and cleavage efficacy were increased in complexes compared with parental ligands and metal salt. Copyright © 2007 John Wiley & Sons, Ltd.     

Structural studies and biological activity evaluation of Pd(II), Pt(II) and Ru(II) complexes containing N‐phenyl,N`‐(3‐triazolyl)thiourea

[MCl(H₂L)(OH₂)]·1.5H₂O (M = Pd(II) ( 1 ) and Pt(II) ( 2 )) and [Ru(H₂L)₂(OH₂)₂]·3H₂O ( 3 ) (H₃L: N‐phenyl, N`‐(3‐triazolyl)thiourea) were synthesized, characterized and tested for their antibacterial activities against Staphylococcus aureus and Escherichia coli bacteria. The thiourea derivative is coordinated to Mⁿ⁺ ions as a mono‐negatively N,S‐bidentate ligand via the enolization of C = S group and triazole N center. The density functional theory calculations reveal that presence of a water molecule in a trans position to triazole ring increased the stability of d⁸ metal ions complexes via the formation of strong Cl…NH intramolecular H‐bond. The cis‐Ru(II)‐isomer with two isoenergetically H₂L^? molecules are more stable than the trans‐analog. Coordination of H₃L to Ru(II) ion did not alter the toxicity of the free ligand, while the interaction with the d⁸ metal ions gave rise to inactive compounds.     

Synthesis,spectral investigation and biological interphase of drug‐based cytotoxic square pyramidal coordination compounds

We have synthesized ciprofloxacin‐based metal complexes of bipyridine derivatives [Cu(CFL)(Aⁿ)Cl].2H₂O (where CFL = ciprofloxacin and A = bipyridines e.g. A¹ = 4‐(4‐fluorophenyl)‐6‐p‐tolyl‐2,2′‐bipyridine, A⁶ = 4‐(4‐(benzyloxy)phenyl)‐6‐(4‐bromophenyl)‐2,2′‐bipyridine, etc.). The ligands and complexes were characterized using analytical (C, H, N elemental analysis, TGA and magnetic measurement) and spectroscopic methods (¹H and ¹³C NMR, FT‐IR, fast atom bombardment mass and reflectance spectroscopy). The products were evaluated by screening for DNA interaction activity on herring sperm DNA and studies suggest intercalative mode of DNA binding. The antimicrobial activity was determined in terms of minimum inhibitory concentration. Superoxide dismutase mimic studies were performed using the NADH/PMS/NBT system. The brine shrimp bioassay was also carried out to study the in vitro cytotoxic properties of the synthesized metal complexes. Copyright © 2012 John Wiley & Sons, Ltd.     

Syntheses,characterization and biological studies of zinc(II), copper(II) and cobalt(II) complexes with Schiff base ligand derived from 2‐hydroxy‐1‐naphthaldehyde and selenomethionine

Novel zinc(II), copper(II), and cobalt(II) complexes of the Schiff base derived from 2‐hydroxy‐1‐naphthaldehyde and D, L ‐selenomethionine were synthesized and characterized by elemental analysis, IR, electronic spectra, conductance measurements, magnetic measurements and powder XRD. The analytical data showed the composition of the metal complex to be ML(H₂O), where L is the Schiff base ligand and M = Co(II), Cu(II) and Zn(II). IR results confirmed the tridentate binding of the Schiff base ligand involving azomethine nitrogen, naphthol oxygen and carboxylato oxygen atoms. ¹H NMR spectral data of lithium salt of the Schiff base ligand [Li(HL)] and ZnL(H₂O) agreed with the proposed structures. The conductivity values of complexes between 12.50 and 15.45 S cm² mol^?1 in DMF suggested the presence of non‐electrolyte species. The powder XRD studies indicated that Co(II) complex is amorphous, whereas Cu(II) and Zn(II) complexes are crystalline. The results of antibacterial and antifungal screening studies indicated that Li(HL) and its metal complexes are active, but CuL(H₂O) is most active among them. Copyright © 2010 John Wiley & Sons, Ltd.     

Crystal structures and antimicrobial and cytotoxic activities of zinc(II), nickel(II) and copper(II) complexes of N‐(piperidylthiocarbonyl)benzamide

A new zinc(II) complex of N‐(piperidylthiocarbonyl)benzamide, [ZnL₂], has been synthesized and characterized using elemental analysis, Fourier transform infrared and ¹H NMR spectroscopies. X‐ray diffraction indicates that [ZnL₂] presents a tetrahedral structure within an O₂S₂ donor set, which is different from analogous square planar [NiL₂] and [CuL₂] available in the literature. The antimicrobial activities of [ZnL₂], [NiL₂] and [CuL₂] were evaluated against fungi and bacteria. The results show that [ZnL₂] is the best for control of the studied fungi and bacteria, and its antimicrobial activity is close to that exhibited by commercial products. The relationship between the structures and antimicrobial activities of the complexes was further investigated using density functional theory calculations. It is elucidated that the increase of the polarity of carbonyl and thiocarbonyl groups determines antifungal and antibacterial activities. Moreover, the cytotoxicity of the complexes was tested against human cancer cells (hepatocellular carcinoma (SK‐Hep‐1) and breast carcinoma (MCF‐7)). The [CuL₂] complex is found to be the most cytotoxic. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis,spectroscopic and the biological activity studies of thiosemicarbazones containing ferrocene and their copper(II) complexes

Two Schiff bases, 1-acetylferrocene thiosemicarbazone (HL¹) and 1,1′-diacetyl-ferrocene dithiosemicarbazone (H₂L²) and their copper(II) complexes were prepared and characterized by elemental analysis, magnetic susceptibility, conductivity, and spectral (IR, UV–Vis, ESR) measurements The IR spectra showed that HL¹ acts as neutral or monobasic bidentate ligand, coordinating to copper(II) through either thiono- or thiolo-sulphur and azomethine-N atoms, whereas H₂L² is a neutral or dibasic mononucleating or binucleating quadridentate ligand coordinating through the same atoms. Other spectral measurements indicate that complexes [(L¹)₂Cu], [(L²)Cu] and [(HL¹)₂Cu]X₂, X?=?Cl, Br or ClO₄ have square-planar geometry around copper(II) while [(HL¹)CuX₂] and [(H₂L²)Cu₂X₄], X?=?Cl or Br, have distorted tetrahedral geometry. The biological activity studies of the complexes and the free ligands towards two gram positive and two gram negative bacteria and one fungal species have been studied and the potential is related to the nature and structure of the tested compounds.