Structural forms in complexes of 2,9-dimethyl-1,10-phenanthroline with simple salts of copper(I) and other univalent ‘closed shell’ species

Syntheses, spectroscopic and structural characterizations of a series of Cu(I)-phenanthroline complexes are reported. A single crystal X-ray structure determination is recorded for CuNO₃:dmp:MeCN (1:1:1), ‘dmp’ = 2,9-dimethyl-1,10-phenanthroline, showing it to be isomorphous with its previously studied tetrafluoroborate, perchlorate and hexafluorophosphate, and silver(I) perchlorate counterparts, the metal atom lying in a trigonal planar [(N^∧N)Cu(NCMe)] coordination environment, the anion not being coordinated. Structure (re-) determinations are also reported for a number of salts of the [Cu(dmp)₂]⁺ cation: the perchlorate, isomorphous with numerous other salts, not only of copper(I), but also lithium(I)), also the unsolvated nitrate, and a solvated form of the chloride.     

Design,synthesis, and biological properties of triazole derived compounds and their transition metal complexes

Triazole derived Schiff bases and their metal complexes (cobalt(II), copper(II), nickel(II), and zinc(II)) have been prepared and characterized using IR, ¹H and ¹³C NMR, mass spectrometry, magnetic susceptibility and conductivity measurements, and CHN analysis data. The structure of L², N-[(5-methylthiophen-2-yl)methylidene]-1H-1,2,4-triazol-3-amine, has also been determined by the X-ray diffraction method. All the metal(II) complexes showed octahedral geometry except the copper(II) complexes, which showed distorted octahedral geometry. The triazole ligands and their metal complexes have been screened for their in vitro antibacterial, antifungal, and cytotoxic activity. All the synthesized compounds showed moderate to significant antibacterial activity against one or more bacterial strains. It is revealed that all the synthesized complexes showed better activity than the ligands, due to coordination.     

N-terminal fragment of the anti-angiogenic human endostatin binds copper(II) with very high affinity

A histidine-rich peptide HSHRDFQPVLHL-NH₂ (L), identical with the N-terminal fragment of the anti-angiogenic human endostatin has been synthesized. Endostatin is a recently identified broad spectrum angiogenesis inhibitor, which inhibits 65 different tumor types. The N-terminal 25-mer peptide fragment of human endostatin has the same antitumor effect as the entire protein. The zinc(II) binding is crucial for the antitumor effect in both cases. Our peptide may provide all critical interactions for zinc(II) binding present in the N-terminal 25-mer peptide fragment. In addition, the N-terminus of human endostatin has a supposedly high affinity binding site for copper(II), similar to human serum albumin. Since copper(II) is intimately involved in angiogenesis, this may have biological relevance.In order to determine the metal binding properties of the N-terminal fragment of endostatin, we performed equilibrium, UV-visible (UV-vis), CD, EPR and NMR studies on the zinc(II) and copper(II) complexes of L. In the presence of zinc(II) the formation of a stable {NH₂, 3N_im, COO⁻} coordinated complex was detected in the neutral pH-range. This coordination mode is probably identical to that present in the zinc(II) complex of the above mentioned N-terminal 25-mer peptide fragment of human endostatin. Moreover, L has extremely high copper(II) binding affinity, close to those of copper-containing metalloenzymes, and forms albumin-like {NH₂, N⁻, N⁻, N_im} coordinated copper(II) complex in the neutral pH-range, which may suggest that copper(II) binding is involved in the biological activity of endostatin.     

Nickel(II) complexes of the multihistidine peptide fragments of human prion protein

Nickel(II) complexes of the peptide fragments of human prion protein containing histidyl residues both inside and outside the octarepeat domain have been studied by the combined application of potentiometric, UV-visible and circular dichroism spectroscopic methods. The imidazole-N donor atoms of histidyl residues are the exclusive metal binding sites below pH 7.5, but the formation of stable macrochelates was characteristic only for the peptide HuPrP(76-114) containing four histidyl residues. Yellow colored square planar complexes were obtained above pH 7.5-8 with the cooperative deprotonation of three amide nitrogens in the [N_im,N⁻,N⁻,N⁻] coordination mode. It was found that the peptides can bind as many nickel(II) ions as the number of independent histidyl residues. All data supported that the complex formation processes of nickel(II) are very similar to those of copper(II), but with a significantly reduced stability for nickel(II), which shifts the complex formation reactions into the slightly alkaline pH range. The formation of coordination isomers was characteristic of the mononuclear complexes with a significant preference for the nickel(II) binding at the histidyl sites outside the octarepeat domain. The results obtained for the two-histidine fragments of the protein, HuPrP(91-115), HuPrP(76-114)H85A and HuPrP(84-114)H96A, made it possible to compare the binding ability of the His96 and His111 sites. These data reveal a significant difference in the nickel(II) and copper(II) binding sites of the peptides: His96 was found to predominate almost completely for nickel(II) ions, while the opposite order, but with comparable concentrations, was reported for copper(II).     

Transition metal complexes bearing atropisomeric saturated NHC ligands

From achiral imidazolinium salts, chiral transition metal complexes containing an N-heterocyclic carbene (NHC) ligand were prepared (metal = palladium, copper, silver, gold, rhodium). Axial chirality in these complexes results from the formation of the metal-carbene bond leading to the restriction of rotation of dissymmetric N-aryl substituents about the C–N bond. When these complexes exhibited a sufficient configurational stability, a resolution by chiral high-performance liquid chromatography (HPLC) on preparative scale enabled isolation of enantiomers with excellent enantiopurities (>99% ee) and good yields. A study of the enantiomerization barriers revealed the effect of the backbone nature as well as the type of transition metal on its values. Nevertheless, the evaluation of palladium-based complexes in asymmetric intramolecular α-arylation of amides demonstrated that the ability to induce an enantioselectivity cannot be correlated to the configurational stability of the precatalysts.     

New dinuclear copper(II) and zinc(II) complexes for the investigation of sugar–metal ion interactions

We have studied the binding interactions of biologically important carbohydrates (d-glucose, d-xylose and d-mannose) with the newly synthesized five-coordinate dinuclear copper(II) complex, [Cu₂(hpnbpda)(μ-OAc)] (1) and zinc(II) complex, [Zn₂(hpnbpda)(μ-OAc)] (2) [H₃hpnbpda = N,N′-bis(2-pyridylmethyl)-2-hydroxy-1,3-propanediamine-N,N′-diacetic acid] in aqueous alkaline solution. The complexes 1 and 2 are fully characterized both in solid and solution using different analytical techniques. A geometrical optimization was made of the ligand H₃hpnbpda and the complexes 1 and 2 by molecular mechanics (MM+) method in order to establish the stable conformations. All carbohydrates bind to the metal complexes in a 1:1 molar ratio. The binding events have been investigated by a combined approach of FTIR, UV–vis and ¹³C NMR spectroscopic techniques. UV–vis spectra indicate a significant blue shift of the absorption maximum of complex 1 during carbohydrate coordination highlighting the sugar binding ability of complex 1. The apparent binding constants of the substrate-bound copper(II) complexes have been determined from the UV–vis titration experiments. The binding ability and mode of binding of these sugar substrates with complex 2 are indicated by their characteristic coordination induced shift (CIS) values in ¹³C NMR spectra for carbon atoms C1, C2, and C3 of sugar substrates.     

Characterization of cadmium- and lead- phytochelatin complexes formed in a marine microalga in response to metal exposure

Phytochelatins (PC_n) are thiol-containing peptides with general structure (-Glu-Cys)_n-Gly enzymatically synthesized by plants and algae in response to metal exposure. They are involved in the cellular detoxification mechanism for their capability to form stable metal-phytochelatin complexes. The speciation of Cd and Pb complexes with phytochelatins has been studied in laboratory cultures of the marine diatom Phaeodactylum tricornutum. An approach based on size-exclusion chromatography (SEC) with off-line detection of phytochelatins, by reverse-phase HPLC, and metal ion, by atomic absorption spectrometry, has been used. The formation of Cd- and Pb-PC_n complexes with n-value from 3 to 6 was demonstrated. The metal-PC_n complexes formed with Cd appear to be different from those formed with Pb for the number of molecules of peptide involved in the complex and for the amount of the metal ion bound. The chromatographic behaviour of metal-PC_n complexes is consistent with Pb-PC_n complexes in which only a molecule of peptide binds the metal ion, and with Cd-PC_n complexes containing two or more molecules of peptide. The metal/peptide molar ratio in Cd-PC_n complexes was higher that in Pb-PC_n complexes. The formation of Cd- or Pb-PC₂ complexes was not demonstrated, probably for a dissociation during the cellular extract preparation. The effectiveness of phytochelatins in the detoxification of these two metal ions in this alga is discussed.     

Thermodynamic and structural characterization of the macrochelates formed in the reactions of copper(II) and zinc(II) ions with peptides of histidine

Copper(II) complexes of the peptides Ac-HisSarHis-NH₂, Ac-HisSarHisSarHis-NH₂ and Ac-HisSarHisSarHisSarHis-NH₂ have been studied by potentiometric, UV-Vis, CD and EPR spectroscopic methods. Stability constants for the corresponding zinc(II) complexes have also been reported. The formation of M(II)-2N_im, M(II)-3N_im and M(II)-4N_im bonded macrochelates was suggested in the pH range 5-7. The macrochelates were, however, not stable enough to prevent metal ion hydrolysis in slightly alkaline solutions. In the case of copper(II) complexes, the metal ion promoted deprotonation and coordination of the amide groups of histidyl residues were also suggested. The stability constants of macrochelate complexes were compared to the literature data reported for the macrochelates of the other peptides of histidine. It was found that the thermodynamic stability of macrochelate species is largely influenced by the number and location of histidyl residues in the peptide backbone. The highest stability was obtained for the HXHYH-type sequences, while the distant arrangement of histidyl residues resulted in a significant reduction of the stability constants.     

Spectroscopic studies on the copper(II)—Inosine system

Interactions of inosine derivatives with copper(II) were studied in the pH range 1.4–13 in 50% H₂O-50% DMSO solution. The distinct pH dependence of the optical spectra observed in copper(II)-inosine complexes are correlated to their respective EPR changes as a function of pH. It was concluded that a simple 1:1 complex of copper(II)-inosine is formed in the pH range 1.4–5.0 and bis complexes are present in the pH 5.0–6.2 region solutions of inosine and Cu(II). From pH 6.2 to 7.8 a diamagnetic, hydroxybridged complex dominates. At pH 7.8–9.2 an insoluble, oxybridged species is formed in addition to the soluble paramagnetic Cu(NI)₄ complex. Starting from pH 9.1 the N-polymeric complex is formed which is stable up to pH 12.5, and above pH 12.5 the only species is the Cu(ribose)₂ complex.     

Crystallographic studies of azide, thiocyanate and perchlorate complexes of methemerythrin.

Difference Fourier maps of azide, thiocyanate and perchlorate complexes of methemerythrin from Themiste dyscritum have been calculated at 4 Å, 3.5 Å and 3.5 Å resolution, respectively, with phases from a refined model. N^?₃ and SCN^? bind to the Fe complex in each subunit, indicating the mode of oxygen binding and suggesting a possible route followed by the anions in reaching the complex. ClO^?₄ binds in two different locations on the non-crystallographic 2-fold axes near cysteine 9 and cysteine 50, apparently being held to the protein by peptide amides and lysine side-chains. Binding of ClO^?₄ at these locations away from the Fe complex is observed to have some effect on the active site structure.     

Synthesis, characterization, thermal behavior, and DNA-cleaving studies of cyano-bridged nickel(II)-copper(II) complexes of 4-(pyridin-2-ylazenyl)resorcinol

We present here the syntheses of a mononuclear Cu^II complex and two polynuclear Cu^II Ni^II complexes of the azenyl ligand, 4‐(pyridin‐2‐ylazenyl)resorcinol (HL; 1). The reaction of HL ( 1 ) and copper(II) perchlorate with KCN gave a mononuclear complex [CuL(CN)] ( 4 ). Using 4 , one pentanuclear complex, [{CuL(NC)}₄Ni](ClO₄)₂ ( 5 ) and one trinuclear complex, [{CuL(CN)}₂NiL]ClO₄ ( 6 ), were prepared and characterized by elemental analyses, magnetic susceptibility, molar conductance, IR, and thermal analysis. Stoichiometric and spectral results of the mononuclear Cu^II complex indicated that the metal/ligand/CN ratio was 1 : 1 : 1, and the ligand behaved as a tridentate ligand forming neutral metal chelates through the pyridinyl and azenyl N‐, and resorcinol O‐atom. The interaction between the compounds (the ligand 1 , its Ni^II and Cu^II complexes without CN, i.e., 2 and 3 , and its complexes with CN, 4 – 6 ) and DNA has also been investigated by agarose gel electrophoresis. The pentanuclear Cu₄Ni complex ( 5 ) with H₂O₂ as a co‐oxidant exhibited the strongest DNA‐cleaving activity.     

Copper(II) complexes with peptide fragments encompassing the sequence 122-130 of human doppel protein

Copper(II) complexes of the peptide fragment (Dpl122-130) encompassing the sequence 122-130 of human doppel protein were characterized by potentiometric, UV-Visible, CD and EPR spectroscopic methods. An analogous peptide, in which the aspartate residue was substituted by an asparagine amino acid, was synthesized in order to provide evidence on the possible role of carboxylate group in copper(II) coordination. It was found that the carboxylic group is directly involved in copper(II) coordination at acidic pH, forming the CuLH₂ species with Dpl122-130. This copper(II) complex displayed EPR parameters very similar to those of the analogous complex with the whole doppel protein. At pH higher than 7, the complexes showed magnetic parameters similar to those of the major species of protein formed in the pH range 7-8, with the metal coordination environment consisting of one imidazole and three amide nitrogen atoms. The comparison of Cu-Dpl122-130 binding constant values with those of the prion peptide fragments (PrP106-114), showed that doppel peptide had a higher metal binding affinity at acidic pH whereas the prion peptide fragment binds the metal tightly at physiological pH.     

Electrochemical properties of copper complexes with unsubstituted and substituted 1,10-o-phenanthrolines in N,N-dimethylformamide solvent

The electrochemical reduction of a series of copper(II) complexes with 1,10-o-phenanthrolines, namely the 1:1 and 1:2 metal:ligand complexes with 2,9-dimethylphenanthroline, 4,7-dimethylphenanthroline and unsubstituted phenanthroline, respectively, has been studied in N,N-dimethylformamide using platinum electrodes. As to the 1:2 complexes, the effect of the presence of substituents with different electronic and steric effects on the phenanthroline ligands has been studied with the aim of rationalizing the different values of the standard potentials which have been measured. Furthermore, the possibility of electrogenerating neutral species, with a formally zerovalent copper centre, exhibiting different stability depending on the nature of the ligands, has been ascertained. In out solvent medium, 1:1 complexes have been found to be in equilibrium with the corresponding 1:2 complexes. A scheme for the reduction of solutions of these compounds, including the different equilibria associated to the electrode charge transfers, has been outlined.     

Antifungal and antitumor activity of heterocyclic thiosemicarbazones and their metal complexes: current status

More than 75 substituted thiosemicarbazones and a number of metal complexes of each have been assayed for their antifungal activity. Their activity is significantly affected by the substituted groups attached at both¹ N and⁴ N of the thiosemicarbazone moiety. Greatest activity occurs for 2-substituted pyridine thiosemicarbazones with differences observed for 2-formylpyridine, 2-acetylpyridine and 2-benzoylpyridine derivatives and their metal complexes. Further, there are activity differences for⁴ N-alkyl-,⁴ N-aryl-,⁴ N-dialkyl- and 3-azacyclothiosemicarbazones and their metal complexes as well as changes in the substituent size among each of these subgroups. Cu(II) complexes are often more active than the uncomplexed thiosemicarbazones, with the latter showing similar activity to Ni(II) complexes in many instances. The reduction potential of the thiosemicarbazone ligand in a Cu(II) complex, the strength of the ligand field and various spectral properties can be correlated to the inhibitory activity.     

1,10-Phenanthroline-dithiolate mixed ligand transition metal complexes. Synthesis, characterization and EPR spectroscopy

A series of new N₂S₂ mixed ligand transition metal complexes, where N₂ is phenanthroline and S₂ is 1,2-dithiooxalate (dto) or 1,2-dithiosquarate (dtsq), has been synthesized and characterized. IR spectra reveal that the 1,2-dithiolate ligands are coordinated via the sulfur atoms forming a N₂S₂ coordination sphere. The copper(II) complex [Cu(phen)(dto)] was studied by EPR spectroscopy as a diamagnetically diluted powder. The diamagnetic dilution resulted from doping of the copper complex into the isostructural host lattice of the nickel complex [Ni(phen)(dto)]. The electronic situation in the frontier orbitals of the copper complex calculated from the experimental data is compared to the results of EHT and DFT calculations. Furthermore, one side product, chlorobis(1,10-phenanthroline)copper(I) ethanol solvate hydrate [(phen)₂CuCl]·C₂H₅OH·H₂O, was formed by a reduction process and characterized by X-ray diffraction. In the crystal packing one-dimensional columns of dimers are formed, stabilized by significant π-π interactions.     

Heavy metal intracellular balance and relationship with metallothionein induction in the liver of carp after contamination by silver,cadmium and mercury following or not pretreatment by zinc

Determination of metal levels (copper, zinc, cadmium, silver and mercury) in soluble and insoluble fractions of liver homogenates has been performed after 7 days exposure of carps (Cyprinus carpio) to moderate concentrations of cadmium, silver and mercury in water. Metallothionein (MT) levels have been quantified by a polarographic method before and after the contamination and a subsequent decontamination phase (7 days). The influence of pretreatment by zinc (7 days) has also been evaluated. MT level variations have been interpreted as having regard to inter-related flows of metal between subcellular fractions. Special interest has been focused on heat-stable compound (HSC)-bound heavy metal flows within the cytosol, taking in account that MT is the major component of these ligands. Our data showed differences between the ability of metals to bind cytosolic ligands and HSCs, and their respective potency for MT induction in liver. Regardless of pretreatment, mercury gave the highest increase of liver MT, but the MT level decreased during the decontamination step, especially after pretreatment by zinc. Cadmium and silver gave similar increases, but a significant difference with the control appeared only after the decontamination step with cadmium, while 1 week of contamintion was enough for silver. However, silver binding with MT was achieved only by the end of the decontamination step, while cadmium depicted the highest ratio for HSC-bound toxic metals after the contamination. Our experimental conditions gave the following order of potency for MT induction in liver: mercury silver > cadmium > zinc. Results are discussed comparatively with data obtained with carp gills.     

Synthesis, characterization, and crystal structures of hydrotris(2-mercapto-1-imidazolyl)borate-based zinc(II) and copper(I) complexes

The reaction of the tripod ligand hydrotris(2-mercapto-1-imidazolyl)borate Tm^xylyl with zinc(II) perchlorate in methanol afforded the mononuclear complex of the type [Tm^xylyl-Zn(mim^xylyl)]ClO₄ (1). Whereas under the same conditions, the reaction with copper(II) perchlorate gives rise to the simultaneous formation of the dinuclear copper(I) complex [Tm^xylylCu]₂ (2). The chemical formulae of the complexes have been characterized by elemental chemical analysis, IR-NMR spectroscopies, and single crystal X-ray methods. In complex 1, the zinc(II) atom displays a distorted tetrahedral environment. While in complex 2, the Tm^xylyl ligand bridges the two copper(I) atoms in an asymmetric manner with trigonal geometry. The inverted conformation of the ligand Tm^xylyl at the boron center, allows the B-H units to be directed towards the copper centers. The greater reactivity of the borohydride groups towards metal centers enhances the reduction of Cu(II) to Cu(I). The obtained kinetic results for the methylation reactions of 1 and 2 indicate that these bound thione complexes are less suitable to electrophilic attack than the thiolate ligand.     

Metal complexes with two tri-aza,tri-oxa pendant-armed macrocyclic ligands: Synthesis,characterization, crystal structures and fluorescence studies

Metal complexes of two new tri-aza, tri-oxa macrocycles containing ethyl acetate (L¹) or carboxymethyl (H₂L²) pendant arms with hydrated nitrate or perchlorate salts of alkaline earth, post-transition and lanthanide metal ions have been synthesized and characterized by microanalysis FAB MS, conductivity measurements, IR, UV–Vis spectroscopy and fluorescence emission studies. The synthesis and characterization of the Pb(II) complexes with the armless macrocyclic precursors L (Schiff base macrocycle) and L′ (diaminic reduced macrocycle) are also reported. The crystal structures of complexes [PbL(ClO₄)(H₂O)](ClO₄), [PbL′(ClO₄)](ClO₄) and ([Zn₂L²(Cl)(H₂O)](ClO₄))_∞ have been determined. In both lead(II) complexes, the metal ion is located inside the macrocyclic cavity and is coordinated by all N₃O₃ donor atoms in the complex with L′ but only by the nitrogen atoms present in the ligand in the complex with L. In both cases, the coordination sphere of the metal atom is completed with a perchlorate anion or a water molecule in the iminic complex of L. X-ray studies on the Zn(II) complex show the presence of a supramolecular structure that is consistent with a linear polymer formed alternately by an endomacrocyclic metal atom coordinated to a macrocyclic ligand and an exomacrocyclic metal ion in distorted octahedral and tetrahedral environments, respectively. UV–Vis and fluorescent emission studies were carried out on the ligands L¹ and H₂L² and their metal complexes, but only the luminescence spectra of the Eu(III) and Tb(III) complexes with L¹ in aqueous solution at ca. pH 7 show the characteristic visible emission of the metal. The value of the quantum yield determined for the Eu(III) complex is similar to that reported in the literature for other Eu(III) complexes.     

Mononuclear and dinuclear complexes derived from new potentially heptadentate acyclic Schiff bases

New potentially heptadentate compartmental ligands have been prepared by reaction of o-acetoacetylphenol or 3-formylsalycilic acid with diethylenetriamine or bis-3-aminopropyl-phenylphosphine.These Schiff bases contain an inner O₂N₂X (X = N, P) and an outer O₂O₂ coordination site which can bond, in close proximity, two similar or dissimilar metal ions.With some metal salts (nickel(II), copper(II) and uranyl(VI) acetates) mononuclear, homo- and heterodinuclear complexes have been synthesized. The spectroscopic, magnetic and electrochemical properties of these complexes have been studied. The catalytic activity of a binuclear copper(II) complex towards the oxidation of 3,5-di-t-butylcatechol to the corresponding quinone was also investigated.     

Copper(II) binding to two novel histidine-containing model hexapeptides: evidence for a metal ion driven turn conformation

The solution conformation and the copper(II) binding properties have comparatively been investigated for the two novel hexapeptides Ac-HPSGHA-NH₂ (P2) and Ac-HGSPHA-NH₂ (P4). The study has been carried out by means of CD, NMR, EPR and UV-Vis spectroscopic techniques in addition to potentiometric measurements to determine the stability constants of the different copper(II) complex species formed in the pH range 3-11. The peptides contain two histidine residues as anchor sites for the metal ion and differ only for the exchanged position of the proline residue with glycine. CD and NMR results for the uncomplexed peptide ligands suggest a predominantly unstructured peptide chain in aqueous solution. Potentiometric and spectroscopic data (UV-Vis, CD and EPR) show that both peptides strongly interact with copper(II) ions by forming complexes with identical stoichiometries but different structures. Furthermore, Far-UV CD experiments indicate that the conformation of the peptides is dramatically affected following copper(II) complexation with the P4 peptide adopting a β-turn-like conformation.