Crystal structure, magnetic and electrochemical properties of five-coordinate copper (II) complexes with 1,10-phenanthroline-5,6-dione

Three new five-coordinate Cu^II complexes, [Cu(tpy)(phen-dione)](PF₆)₂, [Cu(phen)(phen-dione)Cl]PF₆ and [Cu(bpy)(phen-dione)Cl]PF₆ (tpy = 2,2′;6′,2″-terpyridine, phen = 1,10-phenanthroline and phen-dione = 1,10-phenanthroline-5,6-dione) have been prepared and characterized by elemental analysis, IR and UV-Vis spectroscopies and cyclic voltammetry.The complex of [Cu(tpy)(phen-dione)](PF₆)₂ crystallized with one molecule of acetonitrile. The ortep drawing of [Cu(tpy)(phen-dione)](PF₆)₂ · CH₃CN shows that the coordination geometry around Cu^II is a distorted trigonal- bipyramid. Due to the steric hindrance of in the unit cell, the tpy ligands in each complex cation cannot interact in a π-π fashion. The effective magnetic moment (μ_eff) of the complexes was measured by the Evans method. The cyclic voltammograms at Pt disk electrode for these complexes display only one reversible Cu(II)/Cu(I) redox couple.     

Syntheses, crystal structure and cytotoxicity of diamine platinum(II) complexes containing maltol

The cationic complexes (1,2-diaminoethane)(maltolato)platinum(II) ([Pt(en)(ma)]+) and (1R,2R-1,2-diaminocyclohexane)(maltolato)platinum(II) ([Pt(R,R-DACH)(ma)]+) have been prepared and the structure of [Pt(R,R-DACH)(ma)]NO3 has been determined by single crystal X-ray diffraction. The geometry of the metal in [Pt(R,R-DACH)(ma)]NO3 is essentially square planar and the maltolate ligand has a geometry similar to other chelate complexes involving this ligand. The cytotoxicities of the compounds have been assessed in the human cell lines HeLa and K562 and the IC50 values are approximately 32 microM in HeLa cells and 26 microM in K562 cells. In these cell lines the cytotoxicity of cisplatin is higher than the maltolate complexes by a factor of 2 to 3 whereas the cytotoxicity of carboplatin is lower than the maltolate complexes.     

DNA interaction of new copper(II) complexes with sulfonamides as ligands

New copper(II) complexes with sulfonamide ligands have been prepared and characterized. Sulfonamide ligands were prepared through a reaction between 8-aminoquinoline and either 2-mesitylene (Hqmesa), 4-tert-butylbenzene (Hqtbsa), or alpha-toluene (Halphaqtsa) sulfonyl chlorides. The structural analysis carried out for complex [Cu(alphaqtsa)(2)] indicated that the local environment of the Cu(II) cation is between a square planar and a tetrahedral geometry, with stacking of the benzene rings of the sulfonyl ligands between neighbor molecules. Powder EPR spectra at room temperature gave rhombic spectra for the [Cu(alphaqtsa)(2)] and [Cu(qmesa)(2)] complexes and an axial spectrum for the [Cu(qtbsa)(2)] complex, probably due to the steric hindrance of the methyl groups. Complexes [Cu(alphaqtsa)(2)] and [Cu(qmesa)(2)] are artificial chemical nucleases that degrade DNA in the presence of sodium ascorbate. A study of the radical scavengers revealed that the ROS (reactive oxygen species) involved in the DNA damage were hydroxyl, singlet oxygen-like species, and superoxide anion.     

Synthesis, physico-chemical studies of manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II) complexes with some p-substituted acetophenone benzoylhydrazones and their antimicrobial activity

Complexes of the type [M(pabh)(H2O)Cl], [M(pcbh)(H2O)Cl] and [M(Hpabh)(H2O)2 (SO4)] where, M = Mn(II), Co(II), Ni(II), Cu(II) and Zn(II); Hpabh = p-amino acetophenone benzoyl hydrazone and Hpcbh = p-chloro acetophenone benzoyl hydrazone have been synthesized and characterized with the help of elemental analyses, electrical conductance, magnetic susceptibility measurements, electronic, ESR and IR spectra, thermal (TGA & DTA) and X-ray diffraction studies. Co(II), Ni(II) and Cu(II) chloride complexes are square planar, whereas their sulfate complexes have spin-free octahedral geometry. ESR spectra of Cu(II) complexes with Hpabh are axial and suggest d(x(2)-y(2) as the ground state. The ligand is bidentate bonding through > C = N--and deprotonated enolate group in all the chloro complexes, whereas, >C = N and >C = O groups in all the sulfato complexes. Thermal studies (TGA & DTA) on [Cu(Hpabh)(H2O)2(SO4)] indicate a multistep decomposition pattern, which are both exothermic and endothermic in nature. X-ray powder diffraction parameters for [Co(pabh)(H2O)Cl] and [Ni(Hpabh)(H2O)2(SO4)] correspond to tetragonal and orthorhombic crystal lattices, respectively. The ligands as well as their complexes show a significant antifungal and antibacterial activity. The metal complexes are more active than the ligand.     

Synthesis and antitumour activity of platinum(II) and platinum(IV) complexes containing ethylenediamine-derived ligands having alcohol, carboxylic acid and acetate substituents. Crystal and molecular structure of [PtL4CL2].H20 where L4 is ethylenediamine-N,N'-diacetate

Several cisplatin analogues of ethylenediamine-derived ligands containing alcohol, carboxylic acid and acetate substituents have been prepared and characterised. Oxidation of some of these square planar platinum(II) complexes using aqueous hydrogen peroxide gave octahedral platinum(IV) complexes, containing trans hydroxo ligands. Acetylation of the hydroxo ligands was achieved by reaction with acetic anhydride, giving complexes which are analogues of the antitumour drug, JM-216. Oxidation of the complex [Pt(H2L4)Cl2], where H2L4 is ethylenediamine-N,N'-diacetic acid, with H2O2 gave the platinum(IV) complex [PtL4Cl2].H2O in which L4 is tetradentate as shown by a crystal and molecular structure. This complex was previously reported to be [Pt(HL4)(OH)Cl2] in which HL4 is tridentate. Several of the complexes were tested for antitumour activity against five human ovarian carcinoma cell lines. IC50 values range from 4.0 microM for cis,trans-PtCl2(OH)2(NH2CH2CH2NHCH2CH2OH) against the CH1 cell line to >25 microM indicating moderate to low activity relative to other platinum complexes.     

The crystal structures of copper(II), manganese(II), and nickel(II) complexes of a (Z)-2-hydroxy-N'-(2-oxoindolin-3-ylidene) benzohydrazide--potential antitumor agents

Mononuclear complexes of Cu(II), Ni(II), and Mn(II) with a new Schiff base ligand derived from indoline-2,3-dione and 2-hydroxybenzohydrazide, [Cu(II)(L)(2)], [Ni(II)(L)(2)], and [Mn(II)L.(AcO).2C(2)H(5)OH] [HL=(Z)-2-hydroxy-N'-(2-oxoindolin-3-ylidene)benzohydrazide], have been prepared. The complexes have been structurally characterized by X-ray crystallography. Among the three complexes, the Cu(II) complex had the novel highest antitumor activity.     

Oxidative DNA damage of mixed copper(II) complexes with sulfonamides and 1,10-phenanthroline. Crystal structure of [Cu(N-quinolin-8-yl-p-toluenesulfonamidate)2(1,10-phenanthroline)

Mixed coordination compounds of Cu(II) with sulfonamides and 1,10-phenanthroline as ligands have been prepared and characterised. Single crystal structural determination of the complex [Cu(N-quinolin-8-yl-p-toluenesulfonamidate)(2)(phen)] shows Cu(II) ions are located in a highly distorted octahedral environment, probably as a consequence of the Jahn-Teller effect. The FT-IR and electronic paramagnetic resonance (EPR) spectra are also discussed. The mixed complexes prepared undergo an extensive DNA cleavage in the presence of ascorbate and hydrogen peroxide. Two of the complexes have higher nucleolytic efficiency than the bis(o-phenanthroline)copper(II) complex.     

Mixed complexes of Pt(II) and Pd(II) with ethylsarcosinedithiocarbamate and 2-/3-picoline as antitumor agents

The [M(ESDT)Cl](n) (M=Pt(II), Pd(II); ESDT=EtO(O)CCH(2)N(CH(3))CS(2)(-), ethylsarcosinedithiocarbamate ion) species have been reacted with 2- or 3-picoline in dichloromethane in order to obtain mixed ligand complexes of the type [M(ESDT)(L)Cl] (L=2-picoline, 3-picoline). The synthesized compounds have been isolated, purified and characterized by means of elemental analyses, (1)H-/(13)C-/(1)H(13)C-HMBC (heteronuclear multiple bonding coherence) NMR and FT-IR spectroscopy. The biological activity of the compounds reported here has been then determined in terms of cell growth inhibition, DNA synthesis inhibition, detection of interstrand cross-links and DNA-protein cross-links, and micronuclei (MN) detection on a panel of tumor cell lines both sensitive and resistant to cisplatin. On the basis of the experimental results, coordination in the above mentioned complexes takes place in a near square-planar geometry, the dithiocarbamate moiety acting as a chelating agent, whereas the two remaining coordination sites are occupied by a chlorine atom and an amino ligand. Above all, [Pt(ESDT)(2-picoline)Cl] complex has shown very encouraging cytotoxicity levels higher or, at least, comparable to those exerted by cisplatin in the same experimental conditions.     

Synthesis, characterization and crystal structure of copper(II) ternary complex with cinoxacin and histamine

In order to enhance the knowledge of how quinolones may exert their antibacterial action, the synthesis of a new copper(II) mixed ligand, containing histamine complex was carried out. Crystal structure of [Cu(hsm)(cnx)NO₃]H₂O shows that Cu(II) cation displays a distorted square pyramidal geometry. Cinoxacinate (cnx) acts as bidentate ligand bonded to the Cu(II) ion through the oxygen atoms of the 3-carboxylate and 4-keto groups and histamine (hsm) is coordinated by the aliphatic amino group and the non protonated nitrogen of imidazole. Molar conductivity, elemental analysis, infrared and electronic spectroscopy have been used to characterize the complex. The results here reported indicate that cnx coordination mode is similar to that found in other complexes reported previously, being only found that metal-ligand distances are slightly different because the asymmetry of the coordination environment. This result also, may support the hypothesis that the mechanism of action of quinolones could be through a copper(II) complex carrier with imidazole ligands in their coordination environment.     

Anti-oxidant, in vitro, in vivo anti-inflammatory activity and antiproliferative activity of mefenamic acid and its metal complexes with manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II)

Some new complexes of mefenamic acid with potentially interesting biological activity are described. The complexes of mefenamic acid [Mn(mef)(2)(H(2)O)(2)], 1, [Co(mef)(2)(H(2)O)(2)], 2, [Ni(mef)(2)(H(2)O)(2)], 3, [Cu(mef)(2)(H(2)O)](2), 4 and [Zn(mef)(2)], 5, were prepared by the reaction of mefenamic acid, a potent anti-inflammatory drug with metal salts. Optical and infrared spectral data of these new complexes are reported. Monomeric six-coordinated species were isolated in the solid state for Mn(II), Ni(II) and Co(II), dimeric five-coordinated for Cu(II) and monomeric four-coordinated for Zn(II). In DMF or CHCl(3) solution the coordination number is retained and the coordinated molecules of water are replaced by solvent molecules. The anti-oxidant properties of the complexes were evaluated using the 1,1-diphenyl-2-picrylhydrazyl, DPPH, free radical scavenging assay. The scavenging activities of the complexes were measured and compared with those of the free drug and vitamin C. We have explored their ability to inhibit soybean lipoxygenase, beta-glucuronidase and trypsin- induced proteolysis. The complex [Mn(mef)(2)(H(2)O)(2)] exhibits the highest antioxidant activity and the highest inhibitory effect against the soybean lipogygenase (LOX), properties that are not demonstrated by mefenamic acid. Their inhibitory effects on rat paw edema induced by Carrageenan was studied and compared with those of mefenamic acid. The complex [Zn(mef)(2)] exhibited a strong inhibitory effect at 0.1 mmol/Kg B.W. (81.5 +/- 1.3% inhibition), superior to the inhibition induced by mefenamic acid at the same dose (61.5 +/- 2.3% inhibition). Mefenamic acid and its metal complexes have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse fibroblast L-929 cell line. The copper(II) complex displays against T24, MCF-7 and L-929 cancer cell lines, IC(50) values in a microM range similar to that of the antitumor drug cis-platin and they are considered for further stages of screening in vitro and/or in vivo as agents with potential antitumor activity.     

Acid-base properties and copper(II) complexes of dipeptides containing histidine and additional chelating bis(imidazol-2-yl) residues

Copper(II) complexes of dipeptides of histidine containing additional chelating bis(imidazol-2-yl) agent at the C-termini (PheHis-BIMA [N-phenylalanyl-histidyl-bis(imidazol-2-yl)methylamine] and HisPhe-BIMA [N-histidyl-phenylalanyl-bis(imidazol-2-yl)methylamine]) were studied by potentiometric, UV-Visible and Electron Paramagnetic Resonance (EPR) techniques. The imidazole nitrogen donor atoms of the bis(imidazol-2-yl)methyl group are described as the primary metal binding sites forming stable mono- and bis(ligand) complexes at acidic pH. The formation of a ligand-bridged dinuclear complex [Cu2L2]4+ is detected in equimolar solutions of copper(II) and HisPhe-BIMA. The coordination isomers of the dinuclear complex are described via the metal binding of the bis(imidazol-2-yl)methyl, amino-carbonyl and amino-imidazole(His) functions. In the case of the copper(II)-PheHis-BIMA system the [NH2, N-(amide), N(Im)] tridentate coordination of the ligand is favoured and results in the formation of di- and trinuclear complexes [Cu2H(-1)L]3+ and [Cu3H(-2)L2]4+ in equimolar solutions. The presence of these coordination modes shifts the formation of "tripeptide-like" ([NH2, N-, N-, N(Im)]-coordinated) [CuH(-2)L] complexes into alkaline pH range as compared to other dipeptide derivatives of bis(imidazol-2-yl) ligands. Although there are different types of imidazoles in these ligands, the deprotonation and coordination of the pyrrole-type N(1)H groups does not occur below pH 10.     

Synthesis, X-ray crystal structures and biomimetic and anticancer activities of novel copper(II)benzoate complexes incorporating 2-(4'-thiazolyl)benzimidazole (thiabendazole), 2-(2-pyridyl)benzimidazole and 1,10-phenanthroline as chelating nitrogen donor ligands

Cu(BZA)(2)(EtOH)(0.5) (1) was generated by the reaction of copper(II) hydroxide with benzoic acid (BZAH). [Cu(TBZH)(2)(BZA)](BZA).0.5TBZH.H(2)O (2) and [Cu(2-PyBZIMH)(2-PyBZIM)(BZA)].1.66EtOH (3) were obtained when 1 reacted with Thiabendazole (TBZH) and 2-(2-pyridyl)benzimidazole (2-PyBZIMH), respectively. [Cu(BZA)(2)(phen)(H(2)O)] (4) was isolated from the reaction of benzoic acid and 1,10-phenanthroline (phen) with copper(II)acetate dihydrate. Molecular structures of 2, 3 and 4 were determined crystallographically. 2 and 3 are hydrogen bonded dimers and trimers, respectively. The copper centres in complexes 2 and 3 are bis-chelate derivatives that have N(4)O ligation and their geometry is very similar being approximately square-pyramidal. However whereas in complex 2 both TBZH ligands are neutral in 3 one of the 2-PyBZIMH chelators is deprotonated on each copper. The structural results for 4 represent a re-examination of this crystallographically known compound for which no hydrogen atom coordinates have been previously reported. It crystallises as a hydrogen bonded dimmer and is a mono-chelate of phen with each copper centre possessing N(2)O(3) ligation and square pyramidal geometry. The catalase and superoxide dismutase (SOD) activities of the four complexes along with those of the known phenanthroline complexes [Cu(mal)(phen)(2)] and [Cu(phendione)(3)](ClO(4))(2) (malH(2)=malonic acid and phendione=1,10-phenanthroline-5,6-dione) were investigated. Complexes 1-4, the metal free ligands and a simple copper(II) salt were assessed for their cancer chemotherapeutic potential against the hepatocellular carcinoma (Hep-G(2)) and kidney adenocarcinoma (A-498) cell lines. TBZH, 2-PyBZIMH and benzoic acid when uncoordinated to a metal centre offer poor chemotherapeutic potential. copper(II) benzoate is significantly more active than the free acid. The bis-chelate derivatives [Cu(TBZH)(2)(BZA)](BZA).0.5TBZH.H(2)O (2) and [Cu(2-PyBZIMH)(2-PyBZIM)(BZA)].1.66EtOH (3) elicit a significant cytotoxic response to the cancer cell lines tested. Replacing TBZH and 2-PyBZIMH with phen to give [Cu(BZA)(2)(phen)(H(2)O)] (4) does not significantly increase the anti-cancer activity.     

Synthesis, characterisation and antimicrobial activity of copper(II) and manganese(II) complexes of coumarin-6,7-dioxyacetic acid (cdoaH2) and 4-methylcoumarin-6,7-dioxyacetic acid (4-MecdoaH2): X-ray crystal structures of [Cu(cdoa)(phen)2].8.8H(2)O and [Cu(4-Mecdoa)(phen)2].13H2O (phen=1,10-phenanthroline)

Two novel coumarin-based ligands, coumarin-6,7-dioxyacetic acid (1) (cdoaH(2)) and 4-methylcoumarin-6,7-dioxyacetic acid (2) (4-MecdoaH(2)), were reacted with copper(II) and manganese(II) salts to give [Cu(cdoa)(H(2)O)(2)].1.5H(2)O (3), [Cu(4-Mecdoa)(H(2)O)(2)] (4), [Mn(cdoa)(H(2)O)(2)] (5) and [Mn(4-Mecdoa)(H(2)O)(2)].0.5H(2)O (6). The metal complexes, 3-6, were characterised by elemental analysis, IR and UV-Vis spectroscopy, and magnetic susceptibility measurements and were assigned a polymeric structure. 1 and 2 react with Cu(II) in the presence of excess 1,10-phenanthroline (phen) giving [Cu(cdoa)(phen)(2)].8.8H(2)O (7) and [Cu(4-Mecdoa)(phen)(2)].13H(2)O (8), respectively. The X-ray crystal structures of 7 and 8 confirmed trigonal bipyramidal geometries, with the metals bonded to the four nitrogen atoms of the two chelating phen molecules and to a single carboxylate oxygen of the dicarboxylate ligand. The complexes were screened for their antimicrobial activity against a number of microbial species, including methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Candida albicans. The metal-free ligands 1 and 2 were active against all of the microbes. Complexes 3-6 demonstrated no significant activity whilst the phen adducts 7 and 8 were active against MRSA (MIC(80)=12.1microM), E. coli (MIC(80)=14.9microM) and Patonea agglumerans (MIC(80)=12.6microM). Complex 7 also demonstrated anti-Candida activity (MIC(80)=22microM) comparable to that of the commercially available antifungal agent ketoconazole (MIC(80)=25microM).     

Cytotoxic effect, differentiation, inhibition of growth and theoretical calculations of an N,N-donor ligands and its platinum(II), palladium(II) and copper(II) complexes

The new pyrazole ligand 5-(2-hydroxyphenyl)-3-methyl-1-(2-pyridylo)-1H-pyrazole-4-carboxylic acid methyl ester (2) and the corresponding Pt(II), Pd(II) and Cu(II) complexes 3-5 have been synthesized as potential anticancer compounds, and characterized using IR, and (1)H NMR as well as mass spectrometry. The 3-D structures of the Cu(II) complexes were determined by quantum mechanic calculation DFT methodology (density functional theory). The cytotoxicity assay of the ligand and complexes has been performed on leukemia cell lines. In general, the complexes showed lower cytotoxicity than cisplatin, and the Pt(II) and Cu(II) complexes were found to be more efficient in the induction of leukemia cell death than the Pd(II) complex. Our investigations indicate that the antiproliferating activity of the Pt(II) and Cu(II) complexes was partly due to the modulation of cellular differentiation.     

In vivo anticancer, anti-inflammatory, and toxicity studies of mixed-ligand Cu(II) complexes of dien and its Schiff dibases with heterocyclic aldehydes and 2-amino-2-thiazoline. Crystal structure of [Cu(dien)(Br)(2a-2tzn)](Br)(H(2)O)

A new series of complexes of the type [Cu(dien)(2a-2tzn)Y(2)] and [Cu(dienXX)(2a-2tzn)Y(2)], where dien=diethylenetriamine and dienXX=Schiff dibase of diethylenetriamine formed with 2-furaldehyde (dienOO), 2-thiophenecarboxaldehyde (dienSS), or pyrrol-2-carboxaldehyde (dienNN); Y=Cl, Br or NO(3); and 2a-2tzn=2-amino-2-thiazoline, were synthesized and their structure established by C, H, N and Cu analysis; IR and electronic spectra; magnetic susceptibility; and molar conductivity. The isolated complexes are monomers, paramagnetic, and electrolytes of types 1:1 or 1:2. In both types of solid state complexes, [Cu(dien)(2a-2tzn)Y(2)] and [Cu(dienXX)(2a-2tzn)Y(2)], dien and its Schiff dibases are bonded to Cu(II) in a tridentate fashion through 3N atoms. The coordination sphere is completed by the endocyclic nitrogen of the thiazoline moiety and by two Cl, Br, or NO(3) groups with distorted octahedral geometry. The proposed structure of these compounds was supported by X-ray analysis of [Cu(dien)(Br)(2a-2tzn)](Br)(H(2)O). The coordination polyhedron around the copper atom can be described as a distorted square pyramid [Cu(dien)(Br)(2a-2tzn)](+). Its basal plane is occupied by the four nitrogen atoms of the dien and thiazoline ligands with Cu-N distances ranging between 1.996(6) and 2.032(3)A, and the axial position is occupied by one of the two bromine atoms (Br1) with a Cu1-Br1 bond distance of 2.782(1)A. The second bromine atom (Br2) is 4.694(2)A from the copper atom, which exists as a discrete anion and is responsible for the cationic nature of the complex. Results regarding toxicity, antitumor, and anti-inflammatory activities of the investigated compounds are promising and allow the selection of a lead compound for further biological studies.     

Synthesis,crystal structure,and nuclease activity of planar mono-heterocyclic base copper(II) complexes

A series of mononuclear copper(II) complexes having a 1:1 molar ratio of copper and the planar heterocyclic base like 1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) are prepared from a reaction of copper(II) nitrate.trihydrate and the base (L) in ethanol or aqueous ethanol at different temperatures. The complexes [Cu(dpq)(NO(3))(2)] (2), [Cu(dpq)(NO(3))(H(2)O)(2)](NO(3)) (3), [Cu(dpq)(NO(3))(2)(H(2)O)(2)].2H(2)O (4.2H(2)O) and [Cu(dppz)(NO(3))(2)(H(2)O)].H(2)O (5.H(2)O) have been characterized by X-ray crystallography. The crystal structures show the presence of the heterocyclic base in the basal plane. The coordination geometries of the copper(II) centers are axially elongated square-pyramidal (4+1) in 2, 3 and 5, and octahedral (4+2) in 4. The nitrate anion in the coordination sphere displays unidentate and bidentate chelating bonding modes. The axial ligand is either H(2)O or NO(3) in these structures giving a Cu-L(ax) distance of approximately 2.4 A. The one-electron paramagnetic complexes (mu approximately 1.8 mu(B)) exhibit axial EPR spectra in DMF glass at 77 K giving g(parallel)>g( perpendicular ) with an A(parallel) value of approximately 170G indicating a [d(x)2(-y)2](1) ground state. The complexes are redox active and display a quasireversible cyclic voltammetric response for the Cu(II)/Cu(I) couple near 0.0 V vs. SCE giving an order of the E(1/2) values as 5(dppz)>2-4 (dpq)>[Cu(phen)(2)(H(2)O)](2+)>1 (phen). The complexes bind to calf thymus DNA giving an order 5 (dppz)>2 (dpq)>[Cu(phen)(2)(H(2)O)](2+)>1 (phen). An effect of the extended planar ring in dpq and dppz is observed in the DNA binding. The complexes show nuclease activity with pUC19 supercoiled DNA in DMF/Tris-HCl buffer containing NaCl in presence of mercaptopropanoic acid as a reducing agent. The extent of cleavage follows the order: [Cu(phen)(2)(H(2)O)](ClO(4))(2)>5>2 approximately 3 approximately 4>1. The bis-phen complex is a better cleaver of SC DNA than 1-5 having mono-heterocyclic base. Mechanistic investigations using distamycin reveal minor groove biding for the phen, dpq complexes, and a major groove binding for the dppz complex 5. The cleavage reactions are found to be inhibited in the presence of hydroxyl radical scavenger DMSO and the reactions are proposed to proceed via sugar hydrogen abstraction pathway. The ancillary ligand is found to have less effect in DNA binding but are of importance in DNA cleavage reactions.     

New Pd(II) and Pt(II) complexes with N,S-chelated pyrazolonate ligands: molecular and supramolecular structure and preliminary study of their in vitro antitumoral activity

New Pd(II) and Pt(II) complexes [ML2] (HL=a substituted 2,5-dihydro-5-oxo-1H-pyrazolone-1-carbothioamide) have been synthesized by reacting K2MCl4 (M=Pd, Pt) or Pd(OAc)2 with beta-ketoester thiosemicarbazones. The structures of seven of these complexes were determined by X-ray diffraction. Although all exhibit a distorted square-planar coordination with trans- or (in one case) cis-[MN2S2] kernels, their supramolecular arrangements vary widely from isolated molecules to 3D-networks. The in vitro antitumoral assays performed with two HL ligands and their metal complexes showed significant cytostatic activity for the latter, with the most active [ML2] derivative (a palladium complex) being about sixteen times more active than cis-DDP against the cisplatinum-resistant cell line A2780cisR.     

Mono- and polynuclear complexes of Pt(II) with polypyridyl ligands. Synthesis, spectroscopic and structural characterization and cytotoxic activity

An array of poly- and mononuclear complexes of Pt(II) with polypyridyl ligands is reported. The framework complexes [(PtCl(2))(2)(bpp)(2)(micro-PtCl(2))](H(2)O)(2) [bpp=2,3-bis(2-pyridyl)pyrazine], [PtCl(2)(micro-tptz)PtClNCPh]Cl [tptz=2,4,6-tris(2-pyridyl)-1,3,5-triazine], and mononuclear PtCl(2)(NH(2)dpt) [NH(2)dpt=4-amino-3,5-bis(2-pyridyl)-1,2,4-triazole] have been prepared and structurally characterized. Both neutral and ionic complexes are present, with bifunctional and monofunctional Pt(II) moieties, whose size and shape enable them to behave as novel scaffolds for DNA binding. Pt(II) complexes were tested for their biological activity. Cell viability assay and flow cytometric analysis demonstrated that these complexes, particularly [PtCl(2)(micro-tptz)PtClNCPh]Cl, were effective death inducers in human colon rectal carcinoma HT29 cells and their cytotoxic activity was higher than that exerted by cisplatin. Morphological analysis of treated HT29 cells, performed by fluorescence microscopy after Hoechst 33258 staining, showed the appearance of the typical features of apoptosis. Moreover, our results suggested that mitochondria are involved in apoptosis induced by Pt(II) complexes in HT29 cells as demonstrated by dissipation of mitochondrial transmembrane potential.     

Spectroscopic and structural investigation of two (2,2′-bipyridyl)bis(N-protected-aminoacidato)copper(II) complexes,two compounds containing truly CuN2O2 chromophore

The compounds of formula [Cu(bipy)(acleuO)₂] (1) and [Cu(bipy)(ts-β-alaO)₂] (2) (bipy = 2,2′-bipyridil, acleuO = N-acetyl-DL-leucinate anion, ts-β-alaO = N-tosyl-β-alaninate anion) were synthesized and characterized by means of spectroscopic and structural measurements. Complex (1) crystallizes in the monoclinic space group C2/c with cell parameters a = 17.465(4), b = 19.740(5), c = 9.080(2) Å, β = 115.0(1)° with Z = 4; complex (2) crystallizes in the triclinic space group P$\text{1}$, with cell parameters a = 14.489(3), b = 14.308(3), c = 8.659(1) Å, α = 75.0(1), β = 74.6(1), γ = 66.6(1)°, Z = 2. Both structures were solved by conventional Patterson and Fourier methods and refined to R factors of 4.10 and 3.8% respectively. In both crystals the Cu atom is four-coordinated by the nitrogen atoms of a bipy molecule and two carboxylate oxygens of two N-protected aminoacid anions acting as unidentate ligands. The only significant difference between the coordination geometry of (1) and (2) is in the tetrahedral distortion of the coordination plane. Complex (2) is strictly planar, while in complex (1) the distortion expressed by the dihedral angle between the (N)(1)CuN(1′) and O(1)CuO(1′) planes is 20.8°. The electronic and EPR results agree with these different coordination geometries. The infra-red data are consistent with a truly monodentate carboxylate group. The spectroscopic results on a series of previously investigated [Cu(bipy)(N-protected aminoacidato)²] complexes of unknown structures are discussed again in the light of the present structural reports.     

Unusual coordinating behavior by three non-steroidal anti-inflammatory drugs from the oxicam family towards copper(II). Synthesis, X-ray structure for copper(II)-isoxicam, -meloxicam and -cinnoxicam-derivative complexes, and cytotoxic activity for a copper(II)-piroxicam complex

Cytotoxic tests recently performed at National Cancer Institute, NCI (USA), on [Cu(HPIR)(2)(DMF)(2)], 1, (H(2)PIR=piroxicam, 4-hydroxy-2-methyl-N-pyridin-2-yl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide) a widely used non-steroidal anti-inflammatory drug, NSAID [see R. Cini, G. Giorgi, A. Cinquantini, C. Rossi, M. Sabat, Inorg. Chem. 29 (1990) 5197-5200, for synthesis and structural characterization, DMF=dimethylformamide] (NSC #624662) by using a panel of ca. 50 human cancer cells, showed growth inhibition factor GI(50) values as low as 20microM against several cancer lines, with an average value 54.4microM. The activity of 1 is larger against ovarian cancer cells, non-small lung cancer cells, melanoma cancer cells, and central nervous system cancer cells. The widely used anticancer drug carboplatin (cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II)) (NSC #241240) has average GI(50) value of 102microM. The reactions of copper(II)-acetate with other NSAIDs from the oxicam family were tested and crystalline complexes were obtained and characterized. Isoxicam (H(2)ISO=4-hydroxy-2-methyl-N-(5-methylisoxazol-3-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide) produced [Cu(HISO)(2)].0.5DMF, 2.0.5DMF (DMF=dimethylfomamide). The coordination arrangement is square-planar and the HISO(-) anions behave as ambi-dentate chelators via O(amide),N(isoxazole) and O(enolate),O(amide) donors. Meloxicam (H(2)MEL=4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide) produced [Cu(HMEL)(2)(DMF)].0.25H(2)O, 3.0.25H(2)O. The coordination arrangement is square-pyramidal, the equatorial donors being O(amide),N(thiazole) from two HMEL(-) anions and the apical donor being O(DMF). Unexpectedly, cinnoxicam (HCIN=2-methyl-1,1-dioxido-3-[(pyridin-2-ylamino)carbonyl]-2H-1,2-benzothiazin-4-yl-(3-phenylacrylate)) produced [Cu(MBT)(2)(PPA)(2)] (MBT=3-(methoxycarbonyl)-2-methyl-2H-1,2-benzothiazin-4-olate 1,1-dioxide, PPA=3-phenyl-N-pyridin-2-ylacrylamide).