Synthesis, structure and biomimetic properties of Cu(II)-Cu(II) and Cu(II)-Zn(II) binuclear complexes: possible models for the chemistry of Cu-Zn superoxide dismutase

Four imidazolate-bridged binuclear copper(II)-copper(II) and copper(II)-zinc(II) complexes viz., [(Bipy)(2)Cu-Im-Cu(Bipy)(2)](ClO(4))(3).CH(3)OH, [(Phen)(2)Cu-Im-Cu(Phen)(2)](BF(4))(3).2CH(3)OH, [(Bipy)(2)Cu-Im-Zn(Bipy)(2)](BF(4))(3), and [(Phen)(2)Cu-Im-Zn(Phen)(2)](BF(4))(3), (Bipy=2,2'-Bipyridyl, Phen=1-10-Phenanthroline and Im=imidazolate ion) were synthesized as a possible models for superoxide dismutase (SOD). Complex [(Bipy)(2)Cu-Im-Cu(Bipy)(2)](ClO(4))(3).CH(3)OH has been structurally characterized. This complex crystallizes in the triclinic space group P1, with the unit parameters a=8.88(5) A, b=13.79(17) A, c=20.18(18) A, alpha=76.424(8)(o), beta=85.888(6)(o), gamma=82.213(7). The metal-nitrogen bond length from 1.972-2.273 A and the distance Cu-Cu is 5.92 A. The five-coordinate geometry about the copper(II) ion is square pyramidal. Magnetic moment and electron paramagnetic resonance (e.p.r.) spectral measurements of the homobinuclear complexes have shown an antiferromagnetic exchange interaction. From the e.p.r. and UV-Vis spectral measurement studies, these complexes have been found to be stable (pH 8.5-10.5 for 1, 10.5 for 2,3 and 8.5 for 4). These complexes catalyse the dismutation of superoxide radical (O(2)(-)) at biological pH. All the observations indicate that these complexes act as good possible models for superoxide dismutase.     

X-ray, spectral and biological (antimicrobial and superoxide dismutase) studies of oxalato bridged CuII-NiII and CuII-ZnII complexes with pentamethyldiethylenetriamine as capping ligand

X-band electron spin resonance (ESR) and electronic spectra of oxalatobridged heterodinuclear Cu-Ni and Cu-Zn complexes, viz., [(PMDT)Cu-Ox-Ni(PMDT)](BPh(4))(2).2CH(3)CN and [(PMDT)Cu-Ox-Zn(PMDT)](BPh(4))(2).2CH(3)CN, where PMDT=pentamethyldiethylenetriamine, Ox=oxalate ion have been described. Complex [(PMDT)Cu-Ox-Ni(PMDT)](BPh(4))(2).2CH(3)CN has been structurally characterized. This complex crystallizes in the monoclinic space group, C(2) (No. 5) with the unit parameters a=20.445(4) A, b=14.884(3) A, c=23.174(5) A, alpha=90 degrees, beta=102.693(4) degrees, gamma=90 degrees, V=6880(2) A(3) and Z=4. The structure refined to R=0.0354 and R(w)=0.0853 for 21,109 reflections with I>2 sigma(I) using 765 parameters, shows the presence of a MN(3)O(2) chromophore in a distorted trigonal-bipyramidal (TBP) heterometallic complex with oxalate dianion. Taking with an equatorial Cu-O=2.137(8) A and an axial Cu-O=1.961(6) A coordination site at Cu(II) ion and equatorial Ni-O=2.178(7) A and axial Ni-O=1.994 (9) A coordination site at Ni(II) ion. The Cu-Ni distance is 5.3532(9) A and Cu-C(2)O(4)-Ni unit is planar. The [(PMDT)Cu-Ox-Ni(PMDT)](2+) shows the ESR spectrum of the antiferromagnetic spin exchange with each dinuclear delocalization of the unpaired electron over the unit and spin-doublet ground state which demonstrates the Cu-Ox-Ni core. Antimicrobial and superoxide dismutase (SOD) activities of these complexes have also been measured.     

Different modes of DNA cleavage activity of dihydroxo-bridged dicopper(II) complexes having phenanthroline bases

Dihydroxo-bridged dicopper(II) complexes [(Cu(phen))(2)(mu-OH)(2)](ClO(4))(2) (1), [(Cu(dpq))(2)(mu-OH)(2)](ClO(4))(2) (2) and [(Cu(dppz)(DMF))(2)(mu-OH)(2)](PF(6))(2) (3), where phen, dpq and dppz are 1,10-phenanthroline, dipyridoquinoxaline and dipyridophenazine, respectively, are prepared and their DNA binding and cleavage properties studied. Complex 3 has been structurally characterized by X-ray crystallography. The complexes have a (Cu(2)(mu-OH)(2))(2+) core with an essentially planar arrangement of two CuN(2)O(2) basal planes. The complexes are avid binder to calf thymus DNA (K(app) value of 4.8 x 10(6) and 5.9 x 10(6) M(-1) for 2 and 3, respectively, from ethidium displacement assay) and exhibits significant cleavage of supercoiled (SC) pUC19 DNA in dark in presence of mercaptopropionic acid. Besides, the dpq and dppz complexes display photo-induced DNA cleavage on UV (312 nm) and red light (632.8 nm) irradiations in absence of any additives. Mechanistic investigations reveal minor groove binding for the phen and dpq complexes, and major groove preference for the dppz species. The oxidative DNA cleavage reactions in presence of mercaptopropionic acid as a reducing agent involve hydroxyl radicals. The photo-cleavage reactions at UV light involve singlet oxygen as the reactive species, while similar reactions on red light irradiation (632.8 nm) proceed through the formation of hydroxyl radical. The complexes show significant DNA hydrolase activity in absence of any additives under dark reaction conditions.     

Molecular structure, bioavailability and bioactivity of [Cu(o-phen)2(cnge)](NO3)2.2H2O and [Cu(o-phen)(cnge)(H2O)(NO3)2] complexes

Two Cu(II) complexes with cyanoguanidine (cnge) and o-phenanthroline, [Cu(o-phen)(2)(cnge)](NO(3))(2).2H(2)O (1) and [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)] (2), have been synthesized using different experimental techniques and characterized by elemental analyses, FTIR, diffuse and UV-vis spectra and EPR and magnetic moment measurements techniques. The crystal structures of both complexes were solved by X-ray diffraction methods. Complex (1) crystallizes in the monoclinic space group C2/c with a=12.621(5), b=31.968(3), c=15.39(1)A, beta=111.68(4) degrees, and Z=8 and complex (2) in the monoclinic space group P2(1)/n with a=10.245(1), b=13.923(2), c=12.391(2)A, beta=98.07(1) degrees, and Z=4. The environments of the copper(II) center are trigonal bipyramidal (TBP) for [Cu(o-phen)(2)(cnge)](2+) and an elongated octahedron for [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)]. Solution studies have been performed to determine the species distribution. The superoxide dismutase (SOD) activities of both complexes have also been tested in order to determine if these compounds mimic the enzymatic action of the enzyme SOD that protects cells against peroxide radicals.     

Three new Cu(II) and Cd(II) complexes with 3-(2-pyridyl)pyrazole-based ligand: syntheses, crystal structures, and evaluations for bioactivities

Three new complexes [Cu(L)(2)(NO(3))](NO(3))(H(2)O)(1/2)(CH(3)OH)(1/2) (1), [Cd(L)(2)(NO(3))(2)](H(2)O)(3) (2) and [Cd(L)(2)(ClO(4))(CH(3)OH)](ClO(4))(H(2)O)(1/4)(CH(3)OH) (3) (L=1-[3-(2-pyridyl)pyrazol-1-ylmethyl]naphthalene) were synthesized and characterized by elemental analyses, IR and X-ray diffraction analysis. Among them, the Cu(II) and Cd(II) ions were both coordinated by four N donors from two distinct L ligands via N,N-bidentate chelating coordination mode. Additional weak interactions, such as the face-to-face pi-pi stacking and C-Hcdots, three dots, centeredO H-bonding interactions, linked the mononuclear unit into 1D chain and further into 2D network. Complexes 1-3 were subjected to biological assays in vitro against six different cancer cell lines. All of them exhibited cytotoxic specificity and notable cancer cell inhibitory rate. The interactions of 1-3 with calf thymus DNA were investigated by thermal denaturation, viscosity measurements, spectrophotometric and electrophoresis methods. The results indicate that these complexes bound to DNA by intercalation mode via the ligand L and had different nuclease activities, which were in good agreement with their DNA-binding strength. Moreover, the central metal ions of 1-3 played a vital role in DNA-binding behaviors, DNA-cleavage activities and cytotoxicities, whereas the contribution of the different counter anions to their bioactivities also should not be ignored.     

Isatin-Schiff base copper(II) complexes and their influence on cellular viability

Some copper(II) complexes with isatin (isa) or imine ligands derived from isatin were prepared, characterized by analytical and spectroscopic techniques, and had their biological activity toward proliferation of two different cell types verified. These complexes exhibit keto-enolic equilibria in aqueous solution, very dependent of pH, although isolated in the solid state in one defined form, and this type of equilibrium was previously verified to be crucial for their catalytic activity in the oxidation of carbohydrates, through intermediary generation of reactive oxygen species. Herein, biological studies carried out with tumor cells of different origin such as human neuroblastoma (SH-SY5Y) and promonocytic (U937) cells showed that these compounds exert different toxicity. In particular, while compounds [Cu(isaen)(H(2)O)]ClO(4).2H(2)O 2, [Cu(isahist)(H(2)O)](ClO(4))(2)4 and [Cu(isa)(2)]ClO(4)6 are not toxic for both cell lines at the concentrations used in this study, compounds [Cu(isapn)](ClO(4))(2)1, [Cu(isaepy)(2)](ClO(4))(2).2H(2)O 3 and [Cu(isami)(H(2)O)]ClO(4)5 are cytotoxic, with the compound 3 being the most effective. In these compounds, isaen, isahist, isapn, isaepy and isami stand for imine ligands prepared by condensation of ethylenediamine (en), histamine (hist), 1,3-diaminopropane (pn), 2-aminoethylpyridine (epy), and 8-aminoquinoline (ami) with isatin (isa). Cells treated with these compounds were committed to the apoptotic program as evidenced by cytofluorimetric analyses of cell cycle. Moreover, the toxicity of compound 5 was equivalent for both cell lines while the compound 1 was almost not toxic at 24h for SH-SY5Y cells where only an arrest in G1 phase was observed. Compound 3 was more efficient in inducing cell death and also in this case a striking effect on U937 cells (apoptotic cells 68% compared with 11% of SH-SY5Y) was observed. Therefore, the results indicated that their activity seems to be cell type specific.     

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.     

In vitro anti-tumour effect of 1,10-phenanthroline-5,6-dione (phendione), [Cu(phendione)3](ClO4)2.4H2O and [Ag(phendione)2]ClO4 using human epithelial cell lines

The anti-cancer chemotherapeutic potential of 1,10-phenanthroline-5,6-dione (phendione), [Cu(phendione)(3)](ClO(4))(2).4H(2)O and [Ag(phendione)(2)]ClO(4) were determined using four human cells lines, i.e. two neoplastic (A-498 and Hep-G2) and two non-neoplastic (CHANG and HK-2). All of the phendione derivatives induced a concentration-dependant decrease in the viability of the four cell lines, with [Cu(phendione)(3)](ClO(4))(2).4H(2)O displaying greatest activity. In comparative studies, IC(50) values obtained with the two neoplastic cell lines showed a cytotoxic response which was between 3 and 35 times greater than that observed for the metal-based anti-cancer agent, cisplatin. Furthermore, metal-phendione complexes, rather than simple solvated metal ions, were responsible for the observed cytotoxicity. Despite the high level of potency associated with these compounds they did not display an apparent cyto-selective profile, as they reduced the viability of both neoplastic and non-neoplastic cells. However, selected mechanistic studies showed that phendione and its metal complexes inhibited DNA synthesis which did not appear to be mediated through intercalation. Ames testing highlighted that all three compounds and their phase I metabolites were non-mutagenic, unlike cisplatin. Taken together, these results suggest that phendione and its Cu(II) and Ag(I) complexes may be capable of acting as highly effective anti-cancer therapies, which with careful administration could provide very potent and effective alternatives to cisplatin.     

Syntheses,characterization and DNA-binding studies of ruthenium(II) terpyridine complexes: [Ru(tpy)(PHBI)]2+ and [Ru(tpy)(PHNI)]2+

Two novel tridentate ligands, 2-(2-benzimidazole)-1,10-phenanthroline (PHBI) and 2-(2-naphthoimidazole)-1,10-phenanthroline (PHNI), and their heteroleptic complexes [Ru(tpy)(PHBI)](ClO(4))(2).2H(2)O (1) and [Ru(tpy)(PHNI)](ClO(4))(2).H(2)O (2) (tpy=2,2':6',2"-terpyridyl) have been synthesized and characterized by elemental analysis, mass spectra, 1H NMR, and electronic spectroscopy. The electrochemical behaviors of the two novel complexes were studied by cyclic voltammetry. The DNA-binding properties of the two complexes were investigated by spectroscopic methods and viscosity measurements. The results indicated that the two complexes interact with DNA in different binding modes. Complex 1 may bind to DNA via electrostatic interaction, while complex 2 binds to DNA by partial intercalation via the extended naphthyl ring into the base pairs of DNA.     

Synthesis, characterization, DNA-binding and cleavage studies of [Ru(bpy)2(actatp)]2+ and [Ru(phen)2(actatp)]2+ (actatp=acenaphthereno[1,2-b]-1,4,8,9-tetraazariphenylence)

New ligand acenaphthereno[1,2-b]-1,4,8,9-tetraazariphenylence (actatp) and its complexes [Ru(bpy)(2)(actatp)](ClO(4))(2).2H(2)O (1) (bpy=2,2'-bipyridine) and [Ru(phen)(2)(actatp)](ClO(4))(2).2H(2)O (2) (phen=1,10-phenanthroline) have been synthesized and characterized by UV-vis, 1H NMR, and mass spectra. The electrochemical behavior of the two complexes was studied by cyclic voltammetry. The interaction of the two complexes with calf thymus DNA has been investigated by spectrophotometric methods and viscosity measurements. The experimental results suggest that both complexes bind to DNA through an intercalative mode. The circular dichroism signals of the dialysates of the racemic complexes against calf thymus DNA are discussed. When irradiated at 302 nm, both complexes have also been found to promote the photocleavage of plasmid pBR 322 DNA.     

Oxidative strand scission of nucleic acids by a multinuclear copper(II) complex

The compound [Cu(2)(II)(D(1))(H(2)O)(2)](ClO(4))(4).2H(2)O [D(1)=binucleating ligand with tris(2-pyridylmethyl)amine (TMPA) moieties linked in the 5-pyridyl position by a -CH(2)CH(2)- bridge] mediated efficient oxidative cleavage of pBR322 plasmid DNA under reducing conditions. A mononuclear analogue, [Cu(TMPA)(H(2)O)](ClO(4))(2), was less effective at linearizing supercoiled (Form I) plasmid DNA as compared to the binuclear complex. A new method for quenching the copper-dependent reactions has been developed to avoid plasmid scission by the binuclear complex and the standard gel loading buffer. EDTA was not sufficient for retarding copper reaction, but diethyldithiocarbamic acid was capable of inhibiting all reactivity. Investigation of oxidative cleavage of double-helical oligonucleotides by [Cu(2)(II)(D(1))(H(2)O)(2)](ClO(4))(4) confirmed the enhanced reactivity of the binuclear over the mononuclear complex and provided mechanistic insights into the nature of the reaction. Cleavage of DNA required both the binuclear complex and a reductant and likely proceeded through an O(2)-derived intermediate that does not include a diffusible hydroxyl radical. The greater efficiency of the binuclear complex relative to the mononuclear analogue is consistent with their relative abilities to activate dioxygen.     

New unsymmetric dinuclear Cu(II)Cu(II) complexes and their relevance to copper(II) containing metalloenzymes and DNA cleavage

The new homodinuclear complexes, [Cu(2)(II)(HLdtb)(mu-OCH(3))](ClO(4))(2) (1) and [Cu(2)(II)(Ldtb)(mu-OCH(3))](BPh(4)) (2), with the unsymmetrical N(5)O(2) donor ligand (H(2)Ldtb) - {2-[N,N-Bis(2-pyridylmethyl)aminomethyl]-6-[N',N'-(3,5-di-tert-butylbenzyl-2-hydroxy)(2-pyridylmethyl)]aminomethyl}-4-methylphenol have been synthesized and characterized in the solid state by X-ray crystallography.In both cases the structure reveals that the complexes have a common {Cu(II)(mu-phenoxo)(mu-OCH(3))Cu(II)} structural unit.Magnetic susceptibility studies of 1 and 2 reveal J values of -38.3 cm(-1) and -2.02 cm(-1), respectively, and that the degree of antiferromagnetic coupling is strongly dependent on the coordination geometries of the copper centers within the dinuclear {Cu(II)(mu-OCH(3))(mu-phenolate)Cu(II)} structural unit.Solution studies in dichloromethane, using UV-Visible spectroscopy and electrochemistry, indicate that under these experimental conditions the first coordination spheres of the Cu(II) centers are maintained as observed in the solid state structures, and that both forms can be brought into equilibrium ([Cu(2)(HLdtb)(mu-OCH(3))](2+)=[Cu(2)(Ldtb)(mu-OCH(3))](+)+H(+)) by adjusting the pH with Et(3)N (Ldtb(2-) is the deprotonated form of the ligand).On the other hand, potentiometric titration studies of 1 in an ethanol/water mixture (70:30 V/V; I=0.1M KCl) show three titrable protons, indicating the dissociation of the bridging CH(3)O(-) group.The catecholase activity of 1 and 2 in methanol/water buffer (30:1 V/V) demonstrates that the deprotonated form is the active species in the oxidation of 3,5-di-tert-butylcatechol and that the reaction follows Michaelis-Menten behavior with k(cat)=5.33 x 10(-3)s(-1) and K(M)=3.96 x 10(-3)M. Interestingly, 2 can be electrochemically oxidized with E(1/2)=0.27 V vs.Fc(+)/Fc (Fc(+)/Fc is the redox pair ferrocinium/ferrocene), a redox potential which is believed to be related to the formation of a phenoxyl radical.Since these complexes are redox active species, we analyzed their activity toward the nucleic acid DNA, a macromolecule prone to oxidative damage.Interestingly these complexes promoted DNA cleavage following an oxygen dependent pathway.     

Synthesis and DNA binding of mu-[2,9-bis(2-imidazo[4,5-f][1,10]phenanthroline)-1,10-phenanthroline]bis[1,10-phenanthrolinecopper(II)

A binuclear complex [(phen)Cu(mu-bipp)Cu(phen)](ClO(4))(4), where phen=1,10-phenanthroline and bipp=2,9-bis(2-imidazo[4,5-f][1,10]phenanthroline)-1,10-phenanthroline, has been synthesized and its interaction with calf-thymus DNA in the buffer containing 5mM Tris and 50mM NaCl has been studied by means of electronic absorption titration, luminescence titration and viscometric measurements. The absorbance of the complex in the range of 320-400 nm, which is mainly based on bipp showed no obvious change upon addition of DNA, while the peak at 270 nm, which is determined by both phen and bipp decreased by up to 18%. The emission band of the complex around 360 nm decreased remarkably in presence of DNA. The emission quenching of this complex by [Fe(CN)(6)](4-) was depressed greatly when bound to DNA. The relative viscosity of DNA was increased by this complex more significantly than a bipp directed intercalating reagent. These results suggest that this complex binds to calf thymus DNA by intercalation of the two phenanthrolinecopper terminals. The apparent intrinsic binding constant of the complexes with DNA was 1.6 x 10(4)M(-1) as determined by UV-visible titration.     

Magnetic, spectroscopic, structural and biological properties of mixed-ligand complexes of copper(II) with N,N,N,N″,N″-pentamethyldiethylenetriamine and polypyridine ligands

Two new mixed ligand complexes of copper(II) with N,N,N^′,N″,N″-pentamethyldiethylenetriamine and polypyridine ligands have been prepared and characterized by means of spectroscopic, magnetic and single-crystal X-ray diffraction methods. These two complexes are isomorph and isostructure in which the coordination polyhedron about the copper(II) ion is distorted square pyramidal. [Cu(PMDT)(bipy)]²⁺ and [Cu(PMDT)(phen)]²⁺ show an absorption wavelength maximum at 625 and 678 nm, respectively, assigned to the d-d transition. Antibacterial, antifungal and superoxide dismutase activities of these complexes have also been measured. It was observed that [Cu(PMDT)(bipy)](ClO₄)₂ was more effective against P. Pyocyanea and Klebsiella sp. than S. aureus. Similarly, Fusarium sp. was highly susceptible against [Cu(PMDT)(bipy)](ClO₄)₂ but less susceptible against [Cu(PMDT)(phen)](ClO₄)₂.     

(Dien)M(II) (M=Pd, Pt) and (NH3)3Pt(II) complexes of 1-methylcytosine: Linkage and rotational isomerism, metal-promoted deamination, and pathways to dinuclear species

Despite their structural similarity, [Pt(dien)(1-MeC-N3)](2+) (1), [Pd(dien)(1-MeC-N3)](2+) (2), and [Pt(NH(3))(3)(1-MeC-N3)](2+) (3) (with dien=diethylenetriamine and 1-MeC=neutral 1-methylcytosine) behave in part markedly different at strongly alkaline pH (12-13) and at room temperature. While 1 and 2, yet not 3 show linkage isomerization from N3 to N4, deamination of the cytosine nucleobase to 1-methyluracilate occurs with 1 and 3, yet not with 2. Pathways leading to N3,N4-diplatinated 1-MeC(-) complexes (1-MeC(-)=1-methylcytosine, deprotonated at exocyclic amino group N4) have been studied at high pH by starting from 1 and 3, respectively, and adding (dien)Pt(II). It appears that initial migration of the metal entity from N3 to N4, followed by binding of the second metal to the available N3 site, is favored over sequential coordination to N3 and then N4. X-ray crystal data of 1-3 density functional theory (DFT) calculations, and NMR ((1)H, (195)Pt) data are presented.     

Synthesis and DNA binding properties of a cationic 2,2':6',2"-terpyridine cobalt(II) complex containing an oligopeptide

The first example of DNA metallointercalator containing an oligopeptide moiety is presented. The ternary cobalt(II) complex [(DOTA)Co(II)(TPY)](ClO(4))(2) (DOTA=1,4,7,10-tetraaza-cyclododecane-2,9-dione, TPY=2, 2':6',2"-terpyridine) was found to be efficient in binding ct-DNA. The binding constant was determined by spectrophotometric titration. In vitro antitumor studies shows that this complex has significant antitumor activity. The single-crystal of a six coordinated oligopeptide cobalt(II) complex [Co(II)(DOTA)(2)](ClO(4))(2) is also reported. The stabilities and species distributions of Co(II)-DOTA (1:1) and DOTA-Co(II)-TPY (1:1:1) systems were investigated by potentiometry titration.     

Thiol-copper(I) and disulfide-dicopper(I) complex O2-reactivity leading to sulfonate-copper(II) complex or the formation of a cross-linked thioether-phenol product with phenol addition

In order to better understand copper mediated oxidative chemistry via ligand-Cu(I)/O(2) reactivity employing S-donor ligands for copper, O(2)-reactivity studies of the copper(I) complexes (1 and 2, Chart 2) have been carried out with a tridentate N(2)S thiol ligand (1-(N-methyl-N-(2-(pyridin-2-yl)ethyl)amino)propane-2-thiol; L(SH)) or its oxidized disulfide form (L(SS)). Reactions of [L(SH)Cu(I)](+) (1) and [L(SS)(Cu(I))(2)(X)(2)](2+) (2) with O(2) give approximately 90% and approximately 70% yields of [L(SO3)Cu(II)(MeOH)(2)](+) (3), respectively, where L(SO3) is S-oxygenated sulfonate; 3 was characterized by electrospray ionization (ESI) mass spectrometry and X-ray crystallography. Mimicking TyrCys galactose oxidase cofactor biogenesis, a new C-S bond is formed (within new thioether moiety L(SPhOH)) from cuprous complex (both 1 and 2) dioxygen reactivity in the presence of 2,4-tBu(2)-phenolate. In addition, the disulfide ligand (L(SS)) reacts with 2equiv. cupric ion salts and the phenolate to efficiently give the cross-linked product L(SPhOH) in high yield (>90%) under anaerobic conditions. Separately, complex [L(SPhO)Cu(II)(ClO(4))] (4), possessing the cross-linked L(SPhOH), was characterized by ESI mass spectrometry and X-ray crystallography.     

Synthesis and electrochemistry of Co(III) and Co(I) complexes having C5Me5 auxiliary

The synthesis and electrochemistry of half-sandwich type of Co(III) complexes [(C(5)Me(5))Co(bidentate)(CH(3)CN)](BF(4))(2) {bidentate=dppe (1,2-bis(diphenylphosphino)ethane), dppp (1,3-bis(diphenylphosphino)propane), bpy (2,2'-bipyridine), en (ethylenediamine)) are reported. Cyclic voltammograms of [(C(5)Me(5))Co(bidentate)(CH(3)CN)](BF(4))(2) in CH(3)CN s showed two redox couples assignable to Co(II)/Co(III) and Co(I)/Co(II). The Co(I) complex having C(5)Me(5) and dppe was also prepared. Two redox couples of this Co(I) complex, (C(5)Me(5))Co(dppe), in CH(3)CN coincided with those of [(C(5)Me(5))Co(dppe)(CH(3)CN)](BF(4))(2) in spite of the structural change around the metal center.     

The interaction of 5-fluoroorotic acid with transition metals: synthesis and characterisation of Ni(II), Cu(II) and Zn(II) complexes

5-Fluoroorotic acid (H(3)FOro) is a potent inhibitor for some metalloproteins such as dihydroorotase and dihydroorotate dehydrogenase and for thymidylate synthase (nonmetalloprotein) in the human malaria parasite Plasmodium falciparum. To study the coordination chemistry of H(3)Foro, the ammonium salt [NH(4)(+)][H(2)FOro(-)].1H(2)O (1) and the first coordination compounds of H(3)FOro with transition metals [Ni(HFOro(2-))(H(2)O)(4)].1H(2)O (2), [Cu(HFOro(2-))(NH(3))(H(2)O)](n) (3) and [Cu(3)(FOro(3-))(2)(NH(3))(6)(H(2)O)(2)] (4) have been synthesised and characterised by single-crystal X-ray diffraction, IR spectroscopy and by thermogravimetry. Three different coordination modes of 5-fluoroorotic acid have been established. In all cases the ligand is chelated to the metal via an amido-nitrogen and a carboxylate-oxygen but for (3), there is also a carboxylate oxygen from another HFOro(2-) ligand resulting in a polymeric structure and for (4), the second amido-nitrogen in the ororotic acid ring coordinates to give a trinuclear complex. The metal coordination polyhedra are octahedral in (2), square-pyramidal in (3) and square-planar and approximately square-pyramidal in (4). An octahedral coordination geometry including a N(1)/O(61)-chelating HFOro(2-) ligand with four aqua ligands is proposed for the Zn complex [Zn(HFOro(2-)) (H(2)O)(4)].0.5H(2)O (5), based on IR and thermogravimetric data. Extensive hydrogen bonded networks and some ring-ring stacking interactions are observed in each of the structures.     

Spectroscopic and structural characterization of copper(II) and palladium(II) complexes of a lichen substance usnic acid and its derivatives. Possible forms of environmental metals retained in lichens

The metal binding properties of a phenolic lichen substance usnic acid (UA) and its acetyl and enamine derivatives 9-O-acetylusnic acid (MAUA), 7,9-di-O-acetylusnic acid (DAUA), Delta(2,11)-enaminousnic acid (EUA), and N-substituted Delta(2,11)-enaminousnic acids have been studied by synthetic and spectroscopic methods, and the structures of copper(II) and palladium(II) complexes have been established by the X-ray diffraction method. Cu(II) reacted with UA and DAUA to give the binary complexes Cu(UA)(2) x H(2)O and Cu(DAUA)(2), respectively, and Cu(bpy) (bpy=2,2'-bipyridine) formed ternary complexes with UA and DAUA. Pd(II) also reacted with UA, DAUA, EUA, and N-substituted Delta(2,11)-enaminousnic acids to give the corresponding binary complexes. All the isolated complexes are insoluble in water and soluble in most organic solvents. They exhibited very strong absorption and circular dichroism spectral peaks in the UV region. The (1)H-NMR spectrum in CDCl(3) of the Pd(II) complex of N-phenyl-Delta(2,11)-enaminousnic acid (PEUA), Pd(PEUA)(2) x C(6)H(6), showed that the C(4)-proton signal suffered a large upfield shift (0.86 ppm) due to the ring current effect of the N-phenyl moiety. X-Ray crystal structure analysis has been performed for Cu(bpy)(UA)(ClO(4)) x CH(3)OH, Pd(MEUA)(2) x C(6)H(6), and Pd(PEUA)(2) x C(6)H(6). Cu(bpy)(UA)(ClO(4)) x CH(3)OH has a square-pyramidal structure with the two nitrogen atoms of bpy and the two oxygen atoms of the mono-deprotonated B ring of UA in the equatorial positions, while Pd(II) binds with two molecules of MEUA or PEUA in the trans configuration through the nitrogen and oxygen atoms with deprotonation. The N-phenyl ring of PEUA in Pd(PEUA)(2).C(6)H(6) was revealed to be located close to the C(4) proton as indicated by (1)H-NMR. Isolation of Cu(2)(bpy)(2)(UA)(NO(3))(2) x 2H(2)O suggests that UA has two metal binding sites that can form polymeric complexes. The present results substantiate the metal binding ability and the structures of the complexes of usnic acid and other substances from lichens as biomonitors of environmental metal ions.