Phenoxyl-copper(II) complexes: models for the active site of galactose oxidase

 The reaction of the macrocycles 1,4,7-tris (3,5-di-tert-butyl-2-hydroxy-benzyl)-1,4,7-triazacyclononane, L¹H₃, or 1,4,7-tris(3-tert-butyl-5-methoxy-2-hydroxy-benzyl)-1,4,7-triazacyclononane, L²H₃, with Cu(ClO₄)₂·6H₂O in methanol (in the presence of Et₃N) affords the green complexes [Cu^II(L¹H)] (1), [Cu^II(L²H)]·CH₃OH (2) and (in the presence of HClO₄) [Cu^II(L¹H₂)](ClO₄) (3) and [Cu^II(L²H₂)] (ClO₄) (4). The Cu^II ions in these complexes are five-coordinate (square-base pyramidal), and each contains a dangling, uncoordinated pendent arm (phenol). Complexes 1 and 2 contain two equatorially coordinated phenolato ligands, whereas in 3 and 4 one of these is protonated, affording a coordinated phenol. Electrochemically, these complexes can be oxidized by one electron, generating the phenoxyl-copper(II) species [Cu^II(L¹H)]^+ ·, [Cu(L²H)]^+ ·, [Cu^II(L¹H₂)]^2+ ·, and [Cu^II(L²H₂)]^2+ ·, all of which are EPR-silent. These species are excellent models for the active form of the enzyme galactose oxidase (GO). Their spectroscopic features (UV-VIS, resonance Raman) are very similar to those reported for GO and unambiguously show that the complexes are phenoxyl-copper(II) rather than phenolato-copper(III) species. Received: 10 February 1997 / Accepted: 7 April 1997     

Synthesis of copper(II) complexes with 3,5-bis(4,6-dimethylpyrimidin-2-yl)-4H-1,2,4-triazol-4-amine (L). Molecular and crystal structures of L and [Cu2L2Cl4]·2MeCN

A series of copper(II) complexes, i.e. Cu₂LCl₄, CuLCl₂·H₂O and [Cu₂L₂Cl₄]·2MeCN (8), based on a new potentially polytopic ligand, 3,5-bis(4,6-dimethylpyrimidin-2-yl)-4H-1,2,4-triazol-4-amine (3b, L), have been synthesized. The crystal structures of L and [Cu₂L₂Cl₄]·2MeCN were studied by X-ray single crystal analysis. The dinuclear compound [Cu₂L₂Cl₄]·2MeCN represents the first example of structurally characterized metal complexes with 3,5-di(pyrimidin-2-yl)-4H-1,2,4-triazol-4-amines. Both copper atoms have distorted tetragonal-pyramidal 3N + 2Cl environment. Surprisingly, in contrast to the complexes based on 3,5-di(pyridin-2-yl)-4H-1,2,4-triazol-4-amine (pyridinyl analog of L), the compound [Cu₂L₂Cl₄]·2MeCN adopts a dinuclear trans-(N′,N¹,N²)₂ double bridging binding mode which is due to tridentate coordination of two L molecules linking two copper atoms through N¹,N²-triazole and N′-pyrimidine atoms. It seems to be reasonable that it is methyl groups in pyrimidinyl moiety that obstruct the expected dinuclear (N′,N¹,N²,N″)₂ double bridging coordination being one of the most common for 4-substituted 3,5-di(pyridin-2-yl)-4H-1,2,4-triazoles and 3,5-di(pyridin-2-yl)-1,2,4-triazolates. Due to π-π stacking interactions, molecules of Cu₂L₂Cl₄ in the structure of [Cu₂L₂Cl₄]·2MeCN form 1D chains.     

Highly flexible O,O′,N ligands and their Fe, Ni, Cu and Zn complexes

Three new chiral ligands bearing an O,O′,N donor set (O_methoxyO_hydroxyN_pyridine) were synthesised and coordinated to Fe^III, Fe^II, Ni^II, Cu^II and Zn^II to yield complexes with the general formula [M(OON)Cl_x]_y. While the pyridine N and the hydroxy O atoms coordinate strongly to all applied metal ions, the methoxy donor seems not to be involved in coordination, although some evidence for a weak interaction between O_Me and the Zn^II were found in NMR spectra. In the bidentate O′,N coordination mode the new ligands exhibit several coordination geometries as analysed in the solid compounds by XRD, EXAFS and EPR and in solution by UV-Vis absorption, cyclic voltammetry, EXAFS, EPR or NMR spectroscopy.     

Tetra-, penta- and hexacoordinate copper(II) complexes with N3 donor isoindoline-based ligands: Characterization and SOD-like activity

Reaction of 1,3-bis(2′-Ar-imino)isoindolines (HLⁿ, n = 1-7, Ar = benzimidazolyl, N-methylbenzimidazolyl, thiazolyl, pyridyl, 3-methylpyridyl, 4-methylpyridyl, and benzthiazolyl, respectively) with Cu(OCH₃)₂ yields mononuclear hexacoordinate complexes with Cu(Lⁿ)₂ composition. With cupric perchlorate square-pyramidal [Cu^II(HLⁿ)(NCCH₃)(OClO₃)]ClO₄ complexes (n = 1, 3, 4) were isolated as perchlorate salts, whereas with chloride Cu^II(HLⁿ)Cl₂ (n = 1, 4), or square-planar Cu^IICl₂(HLⁿ) (n = 2, 3, 7) complexes are formed. The X-ray crystal structures of Cu(L³)₂, Cu(L⁵)₂, [Cu^II(HL⁴)(NCCH₃)(OClO₃)]ClO₄, Cu^IICl(L²) and Cu^IICl(L⁷) are presented along with electrochemical and spectral (UV-Vis, FT-IR and X-band EPR) characterization for each compound. When combined with base, the isoindoline ligands in the [Cu^II(HLⁿ)(NCCH₃)(OClO₃)]ClO₄ complexes undergo deprotonation in solution that is reversible and induces UV-Vis spectral changes. Equilibrium constants for the dissociation are calculated. X-band EPR measurements in frozen solution show that the geometry of the complexes is similar to the corresponding X-ray crystallographic structures. The superoxide scavenging activity of the compounds determined from the McCord-Fridovich experiment show dependence on structural features and reduction potentials.     

Oxime-functionalized diazamesocyclic derivates and their metal complexes: Effect of the ligand backbones and anions on the generation of novel monomeric and mono-μ-Cl dimeric Cu complexes

Two oxime-functionalized diazamesocyclic derivates, namely, N,N′-bis(acetophenoneoxime)-1,4-diazacycloheptane (H₂L¹) and N,N′-bis(acetophenonoxime)-1,5-diazacyclooctane (H₂L²), have been prepared and characterized. Both ligands (obtained in the hydrochloride form) can form stable metal complexes with Cu^II and Ni^II salts, the crystal structures of which were determined by X-ray diffraction technique. The reactions of H₂L¹ with Cu(ClO₄)₂ and Ni(ClO₄)₂ afford a penta-coordinated mononuclear complex [Cu(H₂L¹)Cl] · ClO₄ (1) and a four-coordinated monomeric [Ni(HL¹)] · ClO₄ (2), in which the ligand is monodeprotonated. The ligand H₂L² also forms a quite similar mononuclear [Ni(HL²)] · ClO₄ complex with Ni(ClO₄)₂, according to our previous work. However, reactions of different Cu^II salts [Cu(ClO₄)₂, CuCl₂ and Cu(NO₃)₂ for 3, and CuSO₄ for 4] with H₂L² in the presence of NaClO₄ yield two unusual mono-μ-Cl dinuclear Cu^II complexes [Cu₂(HL²)₂Cl] · (ClO₄) (3), and [Cu₂(H₂L²)(HL²)Cl] · (ClO₄)₂ · (H₂O)(4). These results indicate that the resultant Cu^II complexes (1, 3 and 4) are sensitive to the backbones of diazamesocycles and even auxiliary anions.     

Oligonucleotides are potent antioxidants acting primarily through metal ion chelation

We report on a rather unknown feature of oligonucleotides, namely, their potent antioxidant activity. Previously, we showed that nucleotides are potent antioxidants in Fe^II/Cu^I/II–H₂O₂ systems. Here, we explored the potential of 2′-deoxyoligonucleotides as inhibitors of the Fe^II/Cu^I/II-induced ·OH formation from H₂O₂. The oligonucleotides [d(A)_5,7,20; d(T)₂₀; (2′-OMe-A)₅] proved to be highly potent antioxidants with IC₅₀ values of 5–17 or 48–85 μM in inhibiting Fe^II/Cu^I- or Cu^II-induced H₂O₂ decomposition, respectively, thus representing a 40–215-fold increase in potency as compared with Trolox, a standard antioxidant. The antioxidant activity is only weakly dependent on the oligonucleotides’ length or base identity. We analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry and ¹H-NMR spectroscopy the composition of the d(A)₅ solution exposed to the aforementioned oxidative conditions for 4 min or 24 h. We concluded that the primary (rapid) inhibition mechanism by oligonucleotides is metal ion chelation and the secondary (slow) mechanism is radical scavenging. We characterized the Cu^I–d(A)₅ and Cu^II–d(A)₇ complexes by ¹H-NMR and ³¹P-NMR or frozen-solution ESR spectroscopy, respectively. Cu^I is probably coordinated to d(A)₅ via N1 and N7 of two adenine residues and possibly also via two phosphate/bridging water molecules. The ESR data suggest Cu^II chelation through two nitrogen atoms of the adenine bases and two oxygen atoms (phosphates or water molecules). We conclude that oligonucleotides at micromolar concentrations prevent Fe^II/Cu^I/II-induced oxidative damage, primarily through metal ion chelation. Furthermore, we propose the use of a short, metabolically stable oligonucleotide, (2′-OMe-A)₅, as a highly potent and relatively long lived (t _1/2 ~ 20 h) antioxidant.     

Copper(II) complexes with monocarboxylate ligands bearing different substituent groups: Synthesis and spectroscopic studies

In our continuing efforts to explore the effects of substituent groups of ligands in the formation of supramolecular coordination structures, seven new Cu^II complexes formulated as [Cu₂(L¹)₄(DMF)₂] (1), {[Cu₂(L¹)₄(Hmta)](H₂O)_0.75}_∞ (2), [Cu₂(L²)₄(2,2′-bipy)₂] (3), [Cu₂(L³)₄(H₂O)₂] (4), [Cu₂(L³)₄(Hmta)]_∞ (5), [Cu₂(L³)₄(Dabco)]_∞ (6) and [Cu₂(L³)₄(Pz)]_∞ (7) with three monocarboxylate ligands bearing different substituent groups HL¹-HL³ (HL¹ = phenanthrene-9-carboxylic acid, HL² = 2-phenylquinoline-4-carboxylic acid, HL³ = adamantane-1-carboxylic acid, Hmta = hexamethylenetetramine, 2,2′-bipy = 2,2′-bipyridine, Dabco = 1,4-diazabicyclo[2.2.2] octane and Pz = pyrazine), have been prepared and characterized by X-ray diffraction. In 1, 2 and 4-7, each Cu^II ion is octahedrally coordinated, and carboxylate acid acts as a syn-syn bridging bidentate ligand. While each Cu^II ion in 3 is penta-coordinated in a distorted square-pyramidal geometry. 1 and 4 both show a dinuclear paddle-wheel block, while 2, 5, 6 and 7 all exhibit an alternated 1D chain structure between dinuclear paddle-wheel units of the tetracarboxylate type Cu₂-(RCO₂)₄ and the bridging auxiliary ligands Hmta, Dabco and Pz. Furthermore, 3 has a carboxylic unidentate and μ_1,1-oxo bridging dinuclear structure with the chelating auxiliary ligand 2,2′-bipy. Moreover, complexes 1-6 were characterized by electron paramagnetic resonance (EPR) spectroscopy.     

Dinuclear Ni(II) and Cu(II) complexes with indolecarboxamide ligand: Synthesis, structure and properties

A potential tetradentate indolecarboxamide ligand, H₄L³ is synthesized and investigated for its coordination abilities towards Ni(II) and Cu(II) ions. Two H₄L³ ligands in their tetra-deprotonated form [L³]⁴⁻, were found to coordinate two metal centers resulting in the formation of [Ni₂(L³)₂]⁴⁻ (5) and [Cu₂(L³)₂]⁴⁻ (6) complexes. The crystal structure of 6 displays the formation of a dinuclear structure where two fully deprotonated ligands, [L³]⁴⁻ hold two copper(II) ions together. Even more interesting is the fact that both deprotonated ligands, [L³]⁴⁻ coordinate the copper ions in an identical and symmetrical fashion. The Na⁺ cations present in the complex 6 stitch together the dinuclear units resulting in the formation of a coordination chain polymer. Four sodium ions connect two dinuclear units via interacting with the O_amide groups. Further, Na⁺ cations were found to coordinate several DMF molecules; some of them are terminal and a few are bridging in nature. The solution state structure (determined by the NMR spectral analysis) of the diamagnetic complex 5 also supported the fact that two deprotonated ligands, coordinate two nickel ions in an identical and symmetrical fashion. Absorption spectral studies reveal that the solid-state square-planar geometry is retained in solution and both complexes do not show any tendency to coordinate potential axial ligands. The variable-temperature magnetic measurements and EPR spectra indicate spin-spin exchange between two copper centers in complex 6. The electrochemical results for both complexes show three irreversible oxidative responses that correspond to the oxidation of first and second metal ion followed by the ligand oxidation, respectively.     

Copper(II) complexes of new pentadentate bis(benzimidazolyl)-dithioether ligands: synthesis, structure, spectra and redox properties

Copper(II) complexes of a series of linear pentadentate ligands containing two benzimidazoles, two thioether sulfurs and a amine nitrogen, viz. N,N^′-bis{4^′-(2″-benzimidazolyl)(methyl)-3^′-thiabutyl}amine(L¹), N,N^′-bis{4^′-(2″-benzimidazolyl)(methyl)-3^′-thiabutyl}N-methylamine (L²), 2,6-bis{4^′-(2″-benzimidazolyl)(methyl)-3^′-thiabutyl}pyridine(L³), N,N^′-bis{4^′-(2″-benzimidazolyl)-2^′-thiabutyl}amine (L⁴), N,N^′-bis{4^′-(2″-benzimidazolyl)-2^′-thiabutyl}N-methylamine (L⁵) and 2,6-bis{4^′-(2″-benzimidazolyl)-2^′-thiabutyl}-3pyridine (L⁶) have been isolated and characterized by electronic absorption and EPR spectroscopy and cyclic and differential pulse voltammetry. Of these complexes, [Cu(L¹)](BF₄)₂ (1) and [Cu(L²)](BF₄)₂ (4) have been structurally characterized by X-ray crystallography. The coordination geometries around copper(II) in 1 and 4 are described as trigonal bipyramidal distorted square based pyramidal geometry (TBDSBP). The distorted CuN₃S basal plane in them is comprised of amine nitrogen, one thioether sulphur and two benzimidazole nitrogens and the other thioether sulfur is axially coordinated. The ligand field spectra of all the complexes are consistent with a mostly square-based geometry in solution. The EPR spectra of complexes [Cu(L¹)](BF₄)₂ (1), [Cu(L¹)](NO₃)₂ (2), [Cu(L²)](BF₄)₂ (4) and [Cu(L³)](ClO₄)₂ (6) are consistent with two species indicating the dissociation/disproportionation of the complex species in solution. All the complexes exhibit an intense CT band in the range 305-395 nm and show a quasireversible to irreversible Cu^II/Cu^I redox process with relatively positive E_1/2 values, which are consistent with the presence of two-coordinated thioether groups. The addition of N-methylimidazole (mim) replaces the coordinated thioether ligands in solution, as revealed from the negative shift (222-403 mV) in the Cu^II/Cu^I redox potential. The present study reveals that the effect of incorporating an amine nitrogen donor into CuN₂S₂ complexes is to generate an axial copper(II)-thioether coordination and also to enforce lesser trigonality on the copper(II) coordination geometry.     

Magneto-structural correlations and DFT calculations in two rare tetranuclear copper(II)-clusters with doubly phenoxo and end-on azido bridges: Syntheses, structural variations and EPR studies

By slightly changing the synthetic conditions, we have prepared two closely related linear tetranuclear Cu^II complexes with the symmetrical ONNO donor tetradentate Schiff-base ligand [H₂L = (OH)C₆H₄(CH₃)CN(CH₂)₃NC(CH₃)C₆H₄(OH)] and with azide ions. These two distinctly coloured crystalline products were characterized by elemental analysis, IR and UV-Vis spectroscopy, CV, EPR spectra and variable temperature magnetic measurements. Single crystal X-ray diffraction studies of the green [Cu₄(μ-L)₂(μ_1,1-N₃)₂(N₃)₂] (1) and the red [Cu₄(μ-L)₂(μ_1,1-N₃)₂(N₃)₂(H₂O)₂] (2) crystals show that the coordination environment of the two μ-phenoxo and μ_1,1-azido bridged isomorphous tetranuclear Cu^II complexes are slightly different. Thus, both complexes are formed by very similar building units, although with a significant variation in the bridging Cu-O(phenoxo)-Cu and Cu-N(azido)-Cu bond angles. The consequences of these structural variations on the magnetic properties have been investigated from both the experimental and theoretical points of view by variable temperature magnetic measurements and DFT calculations.     

Seven-coordinate Mn(II) and Co(II) complexes of the pentadentate ligand 2,6-diacetyl-4-carboxymethyl-pyridine bis(benzoylhydrazone): Synthesis, crystal structure and magnetic properties

The metal complexation properties of a functionalized N₃O₂ donor ligand H₂L², where H₂L² stands for 2,6-diacetyl-4-carboxymethyl-pyridine bis(benzoylhydrazone), are investigated by structural and spectroscopic (IR, ESI-MS and EPR) characterization of its Mn(II) and Co(II) complexes. The ligand H₂L² is observed to react essentially in the same fashion as its unmodified parent H₂L¹ producing mixed-ligand [M(H₂L²)(Cl₂)] complexes (M = Mn^II (1), Co^II (3)) upon treatment with MCl₂. Complexes [M(HL²)(H₂O)(EtOH)]BPh₄ (M = Mn 2, M = Co 4), incorporating the supporting ligand in the partially deprotonated form (HL²)⁻, are formed by salt elimination of the [M(H₂L²)(Cl₂)] compounds with NaBPh₄. Compounds 2 and 4 are isostructural featuring distorted pentagonal-bipyramidal coordinated Mn^II and Co^II ions, with the H₂O and EtOH ligands bound in axial positions. Intermolecular hydrogen bonding interactions of the type M-OH₂?O-M involving the H₂O ligands and the carbonyl functions of the supporting ligand assembles the complexes into dimers. Temperature-dependent magnetic susceptibility measurements (2-300 K) show a substantially paramagnetic Curie behavior for the Mn²⁺ compound (2) influenced by zero-field splitting and significant orbital angular momentum contribution for 4 (high-spin Co^II). The exchange coupling across the Mn^II-OH₂?O-Mn^II bridges in 2 was found to be less than 0.1 cm⁻¹, suggesting that no significant intradimer exchange coupling occurs via this path.     

Interaction of copper(II) and nickel(II) with a bis-amide ligand functionalized with pyridine moieties: Thermodynamic and spectroscopic studies in aqueous solution

We synthesized a new bis-amide ligand derived from the l(+)-tartaric acid. We then determined its protonation constants and the stability constants of the copper(II) and nickel(II) chelates by potentiometry as well as ESI-MS and UV-Vis spectroscopy. We found that both metal ions are able to induce the deprotonation and the coordination of an amide nitrogen donor atom. In the case of copper complexes, the data show the formation of two major species: Cu₂(L₂H₋₃)⁺ and Cu₂(LH₋₄). EPR and XAS experiments led us to precise the relative structure of these compounds. In Cu₂(L₂H₋₃)⁺, each metal center is coordinated by pyridinic and amidic nitrogen atoms of one ligand and by nitrogen and oxygen atoms from pyridine and hydroxyl moieties from the other one. In Cu₂(LH₋₄), the copper centers are coordinated by pyridinic and amidic nitrogen atoms, as well as a deprotonated hydroxyl group of the ligand. In this latter complex, the lower value of the Cu-Cu distance determined from EXAFS experiments and compared to the one of the solid species likely involve the formation of an exogeneous hydroxyl bridge between the two copper centers. With Ni(II) ions, the only one major species is the mononuclear Ni(LH₋₂) complex, in which Ni(II) is held in an octahedral environment with the metal center chelated by the two pyridinic and the two amidic nitrogen atoms, and two oxygen atoms from water molecules.     

Hydrothermal synthesis, crystal structures and properties of new Fe, Co, Ni, and Zn complexes with 6-quinolinecarboxylate: Interplay of coordinative and noncovalent interactions

Reactions of Fe^II, Co^II, Ni^II, and Zn^II salts with 6-quinolinecarboxylic acid (HL) under the hydrothermal conditions afford three monomeric complexes [M(L)₂(H₂O)₄] (M = Fe^II for 1, Co^II for 2, and Ni^II for 3) and a 1-D polymeric species {[Zn(L)₂(H₂O)] · H₂O}_n (4). The crystal structures of the ligand HL and these four complexes have been determined by using the X-ray single-crystal diffraction technique. The results suggest that complexes 1-3 are isostructural, displaying novel 3-D pillar-layered networks through multiple intermolecular hydrogen bonds, whereas in coordination polymer 4, the 1-D comb-like coordination chains are extended to generate a hydrogen-bonded layer, which is further reinforced via aromatic stacking interactions. Solid-state properties such as thermal stability and fluorescence emission of the polymeric Zn^II complex 4 have also been investigated.     

Nickel and copper complexes with few amide-based macrocyclic and open-chain ligands

The present work shows three new amide-based ligands H₂L¹, H₂L² and H₂L³ and their nickel and copper complexes. The X-ray structural analysis substantiate that the ligands constitute a square-based basal plane around the metal center. The crystal structures also show interesting solid state packing due to hydrogen-bonding and various weak C?H interactions. The solution-based spectral studies support the solid-state geometry observed for these complexes. The electrochemical results show that the Ni^3+/2+ and Cu^3+/2+ redox couple primarily depends on the N₄ donors composed of N_amide and N_amine atoms. It was observed that the ligands H₂L¹ and H₂L² are better suited to stabilize the Cu(III) species whereas ligand H₂L³ is ideal for the stabilization of Ni(III) species. On the basis of electrochemical findings, transient Ni³⁺ species were generated and characterized by the absorption spectroscopy.     

Coordination complexes of 4-methylimidazole with Zn<Superscript>II</Superscript> and Cu<Superscript>II</Superscript> in gas phase and in water: a DFT study

A quantum chemistry study of mononuclear metal coordination with four 4-methylimidazole ligands (4-MeIm) was investigated. The four complexes [Cu(4-MeIm)₄]²⁺, [Cu(4-MeIm)₄, H₂O]²⁺, [Zn(4-MeIm)₄]²⁺ and [Zn(4-MeIm)₄, H₂O]²⁺ were studied with particular attention to the Nπ or Nτ possible coordinations of the 4-MeIm ring with the metals, using different DFT methods. The results suggest that the Nτ coordination of 4-MeIm ring to Zn^II or Cu^II is more favorable whatever the level of calculation. In contrast, the addition of one water molecule in the first coordination sphere of the metal ions provides five-coordinated complexes showing no Nπ or Nτ preferences. There is good agreement between the DFT-calculated structure and those available experimentally. When metal ions are four-fold coordinated, they adopt a tetrahedral geometry. When Cu^II and Zn^II are five-fold coordinated, highly symmetric structures or intermediate structures are calculated. Similar energies are calculated for different structures, suggesting flat potential energy surfaces. The addition of implicit solvent modifies the calculated first coordination sphere, especially for [Cu(4-MeIm)₄, H₂O]²⁺ structures. The QTAIM and ELF topological analyses of the interaction between Cu^II and the neutral ligands, clearly indicate a dative bonding with a strong ionic character.     

Synthesis and Biophysical Studies of Bis‐Macrocyclic Cobalt/Copper(II) Complexes Having a Pyridine Spacer with CT DNA and 5′‐GMP

New bis‐macrocyclic complexes of Co^III, 1 , Ni^II, 2 , and Cu^II, 3 , containing pyridyl bridges between 13‐membered macrocyclic subunits, have been synthesized via an in situ one‐pot template condensation reaction (IOPTCR). The proposed structures of these new dinuclear complexes are consistent with the data obtained from elemental analysis, molar conductance, IR, EPR, UV/VIS, ¹H‐ and ¹³C‐NMR, and ESI‐MS. The complexes 2 and 3 possess square‐planar geometry with four secondary N‐atoms coordinated to the metal ion, while complex 1 reveals octahedral geometry in solution due to coordinated H₂O molecules. DNA‐Binding properties of the complexes 1 and 3 were investigated by absorption and emission titrations, cyclic voltammetry, and viscosity measurements. Complexes 1 and 3 are strong DNA binders with binding constants, K_b, of 1.64×10⁵ and 2.05×10⁵ M ^?1, respectively. Hyperchromism, decrease in emission intensity of DNA‐bound ethidium bromide (EB), and changes observed in the viscosity and cyclic voltammograms in the presence of added metal complexes reveals that the complexes bind to DNA predominantly by electrostatic attraction, substantiated by absorption titration with 5′‐GMP.     

3,5-diacetyl-1,2,4-triazol bis(4N-substituted thiosemicarbazone) palladium(II) complexes: synthesis, structure, antiproliferative activity and low toxicity on normal kidney cells

Treatment of ⁴N-monosubstituted bis(thiosemicarbazone) ligands of 3,5-diacetyl-1,2,4-triazol series with lithium tetrachloridopalladate gave the dinuclear complexes of general formula [Pd(μ-H₃L^1-5)]₂, but using dichloridobistriphenylphosphinepalladium(II) salt, the first mononuclear bis(thiosemicarbazone)-palladium-triphenylphosphine complexes of the 3,5-diacetyl-1,2,4-triazol series, [Pd(H₃L^1-5)PPh₃], have been obtained. All the compounds have been characterized by elemental analysis and by IR and NMR spectroscopy, and the crystal and molecular structures of dinuclear complexes [Pd(μ-H₃L³)]₂ and [Pd(μ-H₃L⁵)]₂ as well as mononuclear complexes [Pd(H₃L¹)PPh₃], [Pd(H₃L²)PPh₃], [Pd(H₃L³)PPh₃] and [Pd(H₃L⁴)PPh₃] have been determined by X-ray crystallography. The new compounds synthesized have been evaluated for antiproliferative activity in vitro against NCI-H460, A2780 and A2780cisR human cancer cell lines. Subsequent toxicity study, on normal renal LLC-PK1 cells, shows that all compounds investigated exhibit very low toxicity on kidney cells with respect to cisplatin.     

Synthesis and crystal structure of a copper(II) complex of deprotonated N,N′-bis(2-pyridinecarboxamide)-2,2′-biphenyl: Comparative redox study of CuN4 pyridine amide complexes

A new distorted square planar (two CuN₂ planes making an angle of ∼43°) copper(II) complex [Cu(L⁴)] · 0.5EtOH · 0.5MeOH (1) of a deprotonated tetradentate pyridine amide ligand [H₂L⁴ = N,N′-bis(2-pyridinecarboxamide)-2,2′-biphenyl] has been synthesized and structurally characterized. Absorption and EPR spectroscopic properties have also been studied. The E_1/2 values (Cu^II/Cu^I redox process) of the title complex along with a selected group of structurally characterized CuN₄ pyridine amide complexes with systematically varied structural, electronic/steric, and chelate-ring size effects, imposed by the coordinating ligands, have been determined and the observed trend has been rationalized.     

Solution and solid-state complexes of the potentially tetradentate pyridyl-thiazole ligand 6,6′-bis(4-methylthiazol-2-yl)-2,2′-bipyridine with Co, Ni, Cu, Cd, Hg, Cu and Ag

Reaction of the potentially tetradentate N-donor ligand 6,6′-bis(4-methylthiazol-2-yl)-2,2′-bipyridine (L¹) with the transition metal dications Co^II, Ni^II, Cu^II, Cd^II and Hg^II results in the formation of mononuclear [M(L¹)]²⁺ complexes, in which a planar ligand coordinates to the metals via all four N-donors. In contrast, reaction of L¹ with Cu^I and Ag^I monocations, affords dinuclear double stranded helicate species [M₂(L¹)₂]²⁺ (where M = Cu^I or Ag^I), in which partitioning of the ligand into two bis-bidentate pyridyl-thiazole chelating units allows each ligand to bridge both metal centres. X-Ray crystallography, electrospray mass spectroscopy and NMR spectroscopy reveal that the complexes [M_n(L¹)_m]^z+ (where n = 1, m = 1 and z = 2, when M = Co^II, Ni^II, Cu^II, Cd^II and Hg^II; n = 2, m = 2 and z = 2, when M = Cu^I), retain their solid-state structures in solution. Conversely, whilst ¹H NMR studies suggest that combination of equimolar amounts of Ag(X)(where ) and L¹ (in either nitromethane or acetonitrile) results in the formation of a helicate in solution, in the solid-state, an anion-templating effect gives rise to either mononuclear or dinuclear helicate structures [Ag_n(L¹)_n][X]_n (where n = 2 when X = OTf⁻; n = 1 when ).     

Antioxidant and prooxidant effects of polyphenol compounds on copper-mediated DNA damage

Inhibition of copper-mediated DNA damage has been determined for several polyphenol compounds. The 50% inhibition concentration values (IC₅₀) for most of the tested polyphenols are between 8 and 480 μM for copper-mediated DNA damage prevention. Although most tested polyphenols were antioxidants under these conditions, they generally inhibited Cu^I-mediated DNA damage less effectively than Fe^II-mediated damage, and some polyphenols also displayed prooxidant activity. Because semiquinone radicals and hydroxyl radical adducts were detected by EPR spectroscopy in solutions of polyphenols, Cu^I, and H₂O₂, it is likely that weak polyphenol-Cu^I interactions permit a redox-cycling mechanism, whereby the necessary reactants to cause DNA damage (Cu^I, H₂O₂, and reducing agents) are regenerated. The polyphenol compounds that prevent copper-mediated DNA damage likely follow a radical scavenging pathway as determined by EPR spectroscopy.