Preference For Cu Research Articles

Adsorption and Activation of Ethene in Transition Metal Exchanged Zeolite Clinoptilolite: a Density Functional Study

Ethene adsorption in transition-metal-exchanged clinoptilolite with cations of the d elements (Fe–Cu) and also Pd was examined by density functional theory with the B3LYP functional, using the embedded cluster method in ONIOM. The preferred extraframework cation sites for the divalent cations are those in the large channel A. The monovalent cations Ni+ and Cu+ show little preference toward the available cation sites: they approach a center of negative framework charge, forming shorter M–O bonds as compared with the divalent cations. Periodic model calculations were applied to validate the extraframework site preference of Cu+ cations, and they confirm the ONIOM results, though periodic calculations systematically predict smaller energy gaps between the different cation site occupancies. A dominant component in the formation of the metal cation–adsorbate π-complexes is the electron charge transfer from the filled d orbitals of the transition metal cations to the unoccupied π* orbitals of ethene. Significan...

Removal of copper(II) from an aqueous solution with copper(II)‐imprinted chitosan microspheres

AbstractIon‐imprinted chitosan (CS) microspheres (MIPs) were prepared with Cu(II) as a template and epichlorohydrin as a crosslinker for the selective separation of Cu(II) from aqueous solution. The microspheres showed a higher adsorption capacity and selectivity for the Cu(II) ions than nonimprinted chitosan microspheres (NMIPs) without a template. The results show that the adsorption of Cu(II) on the CS microspheres was affected by the initial pH value, initial Cu(II) concentration, and temperature. The kinetic parameters of the adsorption process indicated that the adsorption followed a second‐order adsorption process. Equilibrium experiments showed very good fits with the Langmuir isotherm equation for the monolayer adsorption process. The maximum sorption capacity calculated from the Langmuir isotherm was 201.66 mg/g for the Cu–MIPs and 189.51 mg/g for the NMIPs; these values were close to the experimental ones. The selectivity coefficients of Cu(II) and other metal ions on the NMIPs indicated a preference for Cu(II). © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

Application of a Fluorescent C-Linked Phenolic Purine Adduct for Selective N7-Metalation of DNA

The C-linked phenolic adduct, C8-(2″-hydroxyphenyl)-2'-deoxyguanosine (o-PhOHdG), has been employed to study the impact of N7-metalation of 2'-deoxyguanosine (dG) within duplex DNA. The phenolic group of o-PhOHdG assists selective metal ion coordination by the N7-site of the attached dG moiety, which is the most important metal binding site in duplex DNA. The biaryl nucleobase probe o-PhOHdG is highly fluorescent in water (Φ(fl) = 0.44), and changes in its absorption and emission were used to determine apparent association constants (K(a)) for binding to Cu(II), Ni(II), and Zn(II). The nucleoside was found to bind Cu(II) (log K(a) = 4.59) and Ni(II) (log K(a) = 3.65) effectively, but it showed relatively poor affinity for Zn(II) (log K(a) = 2.55). The fluorescent nucleobase o-PhOHdG was incorporated into a pyrimidine-rich oligonucleotide substrate (ODN1) and a purine-rich (ODN2) substrate to monitor selective binding of Cu(II) through fluorescence quenching of the enol emission of o-PhOHdG within the DNA substrates. The pyrimidine-rich substrate ODN1 was found to possess greater affinity for Cu(II) than the free nucleobase, while the purine-rich substrate ODN2 exhibited diminished Cu(II) binding affinity. The impact of Cu(II) on duplex stability and structure was determined using UV melting temperature analysis and circular dichroism (CD) measurements. These studies highlight the syn preference for Cu(II)-bound o-PhOHdG within ODN1 duplexes and demonstrate competitive Cu(II) binding by other natural dG nucleobases within ODN2. The metal binding properties of o-PhOHdG are compared to the structurally similar 2-(2'-hydroxyphenyl)benzoxazole (HBO) derivatives and the nucleoside C8-(2-pyridyl)-dG (2PydG) that has also been used to control N7-metal coordination in DNA. Our results show certain advantages to the use of o-PhOHdG that stem from its highly fluorescent nature in aqueous media and provide additional tools for studying the effects of N7-metalation on the structure and stability of duplex DNA.

Metal Selectivity of the Escherichia coli Nickel Metallochaperone, SlyD

SlyD is a Ni(II)-binding protein that contributes to nickel homeostasis in Escherichia coli. The C-terminal domain of SlyD contains a rich variety of metal-binding amino acids, suggesting broader metal binding capabilities, and previous work demonstrated that the protein can coordinate several types of first-row transition metals. However, the binding of SlyD to metals other than Ni(II) has not been previously characterized. To improve our understanding of the in vitro metal-binding activity of SlyD and how it correlates with the in vivo function of this protein, the interactions between SlyD and the series of biologically relevant transition metals [Mn(II), Fe(II), Co(II), Cu(I), and Zn(II)] were examined by using a combination of optical spectroscopy and mass spectrometry. Binding of SlyD to Mn(II) or Fe(II) ions was not detected, but the protein coordinates multiple ions of Co(II), Zn(II), and Cu(I) with appreciable affinity (K(D) values in or below the nanomolar range), highlighting the promiscuous nature of this protein. The order of affinities of SlyD for the metals examined is as follows: Mn(II) and Fe(II) < Co(II) < Ni(II) ~ Zn(II) ≪ Cu(I). Although the purified protein is unable to overcome the large thermodynamic preference for Cu(I) and exclude Zn(II) chelation in the presence of Ni(II), in vivo studies reveal a Ni(II)-specific function for the protein. Furthermore, these latter experiments support a specific role for SlyD as a [NiFe]-hydrogenase enzyme maturation factor. The implications of the divergence between the metal selectivity of SlyD in vitro and the specific activity in vivo are discussed.

Copper-Binding Properties and Structures of Methanobactins from Methylosinus trichosporium OB3b

Methanobactins (mbs) are a class of copper-binding peptides produced by aerobic methane oxidizing bacteria (methanotrophs) that have been linked to the substantial copper needs of these environmentally important microorganisms. The only characterized mbs are those from Methylosinus trichosporium OB3b and Methylocystis strain SB2. M. trichosporium OB3b produces a second mb (mb-Met), which is missing the C-terminal Met residue from the full-length form (FL-mb). The as-isolated copper-loaded mbs bind Cu(I). The absence of the Met has little influence on the structure of the Cu(I) site, and both molecules mediate switchover from the soluble iron methane mono-oxygenase to the particulate copper-containing enzyme in M. trichosporium OB3b cells. Cu(II) is reduced in the presence of the mbs under our experimental conditions, and the disulfide plays no role in this process. The Cu(I) affinities of these molecules are extremely high with values of (6-7) × 10(20) M(-1) determined at pH ≥ 8.0. The affinity for Cu(I) is 1 order of magnitude lower at pH 6.0. The reduction potentials of copper-loaded FL-mb and mb-Met are 640 and 590 mV respectively, highlighting the strong preference for Cu(I) and indicating different Cu(II) affinities for the two forms. Cleavage of the disulfide bridge results in a decrease in the Cu(I) affinity to ∼9 × 10(18) M(-1) at pH 7.5. The two thiolates can also bind Cu(I), albeit with much lower affinity (∼ 3 × 10(15) M(-1) at pH 7.5). The high affinity of mbs for Cu(I) is consistent with a physiological role in copper uptake and protection.

Metal Binding Affinities of Arabidopsis Zinc and Copper Transporters: Selectivities Match the Relative, but Not the Absolute, Affinities of their Amino-Terminal Domains,

HMA2, HMA4, and HMA7 are three of the eight heavy metal transporting P(1B)-type ATPases in the simple plant Arabidopsis thaliana. The first two transport Zn(2+), and the third transports Cu(+). Each protein contains soluble N-terminal metal-binding domains (MBDs) that are essential for metal transport. While the MBD of HMA7 features a CxxC sequence motif characteristic of Cu(I) binding sites, those of HMA2 and HMA4 contain a CCxxE motif, unique for plant Zn(2+)-ATPases. The three MBDs HMA2n (residues 1-79), HMA4n (residues 1-96), and HMA7n (residues 56-127) and an HMA7/4n chimera were expressed in Escherichia coli. The chimera features the ICCTSE motif from HMA4n inserted in place of the native MTCAAC motif of HMA7n. Binding affinities for Zn(II) and Cu(I) of each MBD were determined by ligand competition with a number of chromophoric probes. The challenges of using these probes reliably were evaluated, and the relative affinities of the MBDs were verified by independent cross-checks. The affinities of HMA2n and HMA4n for Zn(II) are higher than that of HMA7n by a factor of 20-30, but the relative affinities for Cu(I) are inverted by a factor of 30-50. These relativities are consistent with their respective roles in metal selection and transportation. Chimera HMA7/4n binds Cu(I) with an affinity between those of HMA4n and HMA7n but binds Zn(II) more weakly than either parent protein does. The four MBDs bind Cu(I) more strongly than Zn(II) by factors of >10(6). It is apparent that the individual MBDs are not able to overcome the large thermodynamic preference for Cu(+) over Zn(2+). This information highlights the potential toxicity of Cu(+) in vivo and why copper sensor proteins are approximately 6 orders of magnitude more sensitive than zinc sensor proteins. Metal speciation must be controlled by multiple factors, including thermodynamics (affinity), kinetics (including protein-protein interactions), and compartmentalization. The structure of Zn(II)-bound HMA4n defined by NMR confirmed the predicted ferredoxin betaalphabetabetaalphabeta fold. A single Zn atom was modeled onto a metal-binding site with protein ligands comprising the two thiolates and the carboxylate of the CCxxE motif. The observed (113)Cd chemical shift in [(113)Cd]HMA4n was consistent with a Cd(II)S(2)OX (X = O or N) coordination sphere. The Zn(II) form of the Cu(I) transporter HMA7n is a monomer in solution but crystallized as a polymeric chain [(Zn(II)-HMA7n)(m)]. Each Zn(II) ion occupied a distorted tetrahedral site formed from two Cys ligands of the CxxC motif of one HMA7n molecule and the amino N and carbonyl O atoms of the N-terminal methionine of another.

International Solvent Extraction Conference – ISEC 2008

1,4- (H₂L¹) and 1,3-phenylene (H₂L²) linked bis-β-diketone ligands as well as corresponding metal complexes of composition M₃(L¹)₃B₆ and M₂(L²)₂B₂ with B = pyridine (Py) or 4-ethylpyridine (EtPy) have been synthesised. Extraction studies involving the systematic variation of the metal, bis-β-Bdiketone and 4-ethylpyridine concentrations have been performed for Co(Il) and Zn(II) in order to probe the solution stoichiometries of the extracted species. Significant synergistic effects were observed when EtPy was present along with the bis-β-diketone ligand in the organic (CHCI₃) phase. Competitive extraction studies (water/chloroform) demonstrated a clear uptake preference for Cu(II) over Co(II), Ni(II), Zn(Il) and Cd(II).

Chemical Issues Addressing the Construction of the Distal Ni[Cysteine-Glycine-Cysteine]2− Site of Acetyl CoA Synthase: Why Not Copper?

The discovery of the metallopeptide Ni(Cysteine-Glycine-Cysteine)(2-), Ni(CGC)(2-), in the A-cluster active site of Acetyl CoA Synthase has prompted the synthesis of many small molecule models which employ M(N(2)S(2)) complexes as metalloligands. In vitro studies have shown that nickel incorporates into the N(2)S(2) binding pocket even when copper is in the enzyme growth medium, while copper is preferentially taken up in the proximal site, displacing the catalytically active nickel. (Darnault, C.; Volbeda, A.; Kim, E.J.; Legrand, P.; Vernede, X.; Lindahl, P.A.; Fontecilla-Camps, J.C. Nat. Struct. Biol. 2003, 10, 271-279.) The work herein has been designed to address the chemical viability of copper(II) within the tripeptide N(2)S(2) ligand set. To this end, a series of CuN(2)S(2)(2-) complexes, the resin-bound, O-Cu(CGC)(2-) (A) and free Cu(CGC)(2-) (B) complexes, as well as Cu(ema)(2-) (C) and Cu(emi)(2-) (D) dianions, have been characterized by UV-vis, electron paramagnetic resonance (EPR), and electrospray ionization mass spectrometry (ESI-MS) spectroscopies, cyclic voltammetry (CV), and, where appropriate, X-ray diffraction studies, and compared to the Ni(II) congeners. EPR spectroscopic results have indicated that, in frozen N,N-dimethylformamide (DMF) solution, the copper complexes are distorted square planar structures with nitrogen and sulfur donors. This is consistent with X-ray diffraction measurements which also show copper(II) in a distorted square planar environment that is bereft of CuN(2)S(2)(2-) intermolecular interactions. Density-functional theory (DFT) calculations resulted in optimized structures that are consistent with crystallographic data and indicated highest occupied molecular orbital (HOMO)-singly occupied molecular orbital (SOMO) gaps of 5.01 and 4.68 eV for C and D, respectively. Optimized structures of Ni(ema)(2-) and Ni(emi)(2-) share the same basic characteristics as the copper(II) congeners. Electrochemical characterization of C and D resulted in a reversible Cu(III/II) couple at -1.20 V and - 1.40 V, respectively. Reactivity studies with Rh(CO)(2)(+) show similar donor capabilities for complexes A-D. Analysis of A shows that transmetalation does not occur. From competitive metal uptake studies on immobilized tripeptide it is concluded that the N(2)S(2)(4-) ligating unit has a slight preference for Cu(2+) over Ni(2+) and that the biosynthetic pathway responsible for constructing the distal site of ACS must be selective for nickel insertion or copper exclusion, or both.

Theoretical study of Cu38−nAun clusters using a combined empirical potential–density functional approach

Thirty-eight atom Cu-Au clusters have been studied because this is a magic size for a complete truncated octahedral cluster. The clusters are investigated using two approaches, at different levels of theory, which are complementary. The first is an empirical potential (EP) approach which is used together with a genetic algorithm (GA) to tackle the problems of global optimization-i.e., searching for lowest-lying energy structures. The second is an ab initio approach based on density functional theory (DFT) which is used to reoptimize the initial EP structures (both global minima and other low energy isomers). Structural distributions and energy landscapes, including calculations of electronic energy gaps for all compositions of Cu(38-n)Au(n), are investigated. The energy competition between different structural motifs and different configurations are studied at the DFT level. The analysis of mixing and segregation effects results in confirmation of the preference for Cu(core)-Au(shell) configurations at the DFT level. Charge transfer is calculated for different structural motifs of Cu(19)Au(19) to study the role of this phenomenon in driving cluster configuration.

A DFT study of the [Cu 2+—(GlyGlyHis – 3H +)] −1 ion complex structure

Conformations of Cu 2+ ion binding to GlyGlyHis (GGH) tripeptide, a model compound for human serum albumin where the Cu 2+ binding site is the N-terminal AspAlaHis, have been studied by many research groups. The specific interactions between GGH and Cu 2+ ion, which is known to form a [Cu 2+—(GlyGlyHis – 3H +)] −1 planar structure in aqueous solution, are studied in terms of optimized structures and energies in B3LYP/6-311+G(d,p) calculations. Five geometries are tried to optimize the [Cu 2+—(GlyGlyHis – 3H +)] -1 planar structures. A Cu 2+-NNNN planar structure involved the four coordination of a terminal amino nitrogen, two deprotonated amide nitrogens, and an imidazole-N3 atom at the deprotonated imidazole ring, has been calculated to be the most stable structure among the [Cu 2+—(GlyGlyHis – 3H +)] −1 complexes. The energy and geometry of the Cu 2+-NNNO coordination structure involving a C-terminal carboxyl oxygen are also calculated to understand the NNNN-coordination preference of Cu 2+ in the [Cu 2+—(GlyGlyHis – 3H +)] -1 complex.

Rationalizing the Effects of Amino Acid Side Chain, Pyridine, and Imidazole on the Assembly and Reversible Disassembly of a Octanuclear Cu(II) Complex

This paper reports the observation of a reversible disassembly process for a previously reported octanuclear Cu(II) complex with imidazole. To identify the factors responsible for the process, five Cu(II) complexes of different nuclearity with different amino acid-derived tetradentate ligands were structurally characterized. The results show that the coordination geometry preference of Cu(II), the tendency of imidazole to act as in-plane ligand, and H-bonding played important role in the formation and disassembly of the octanuclear complex. A general scheme describing the effect of different amino acid side arms, solvents, and exogenous ligands on the nuclearity of the Cu(II) complexes has been presented. The crystals of the complexes also showed formation of multifaceted networks in the resulting complexes.

Insights for size-dependent reactivity of hematite nanomineral surfaces through Cu 2+ sorption

Macroscopic sorption edges for Cu 2+ were measured on hematite nanoparticles with average diameters of 7 nm, 25 nm, and 88 nm in 0.1 M NaNO 3. The pH edges for the 7 nm hematite were shifted approximately 0.6 pH units lower than that for the 25 nm and 88 nm samples, demonstrating an affinity sequence of 7 nm > 25 nm = 88 nm. Although, zeta potential data suggest increased proton accumulation at the 7 nm hematite surfaces, changes in surface structure are most likely responsible for the preference of Cu 2+ for the smallest particles. As Cu 2+ preferentially binds to sites which accommodate the Jahn–Teller distortion of its coordination to oxygen, this indicates the relative importance of distorted binding environments on the 7 nm hematite relative to the 25 nm and 88 nm particles. This work highlights the uniqueness of surface reactivity for crystalline iron oxide particles with decreasing nanoparticle diameter.

Solution structures of the reduced and Cu(I) bound forms of the first metal binding sequence of ATP7A associated with Menkes disease

The coding sequence for the first N-terminal copper binding motif of the human Menkes disease protein (MNK1; residues 2-79) was synthesized, cloned, and expressed in bacteria for biochemical and structural studies. MNK1 adopts the betaalphabetabetaalphabeta fold common to all the metal binding sequences (MBS) found in other metal transport systems (e.g., the yeast copper chaperone for superoxide dismutase CCS, the yeast copper chaperone ATX1 bound to Hg(II), and most recently Cu(I), the bacterial copper binding protein, CopZ, and the bacterial Hg(II) binding protein MerP), although substantial differences were found in the metal binding loop. Similar to ATX1, MNK1 binds Cu(I) in a distorted linear bicoordinate geometry. As with MerP, MNK1 has a high affinity for both Hg(II) and Cu(I), although it displays a marked preference for Cu(I). In addition, we found that F71 is a key residue in the compact folding of MNK1, and its mutation to alanine results in an unfolded structure. The homologous residue in MerP has also been mutated with similar results. Finally, to understand the relationship between protein folding and metal affinity and specificity, we expressed a chimeric MBS with the MNK1 protein carrying the binding motif of MerP (CAAC-MNK1); this chimeric protein showed differences in structure and the dynamics of the binding site that may account for metal specificity.

A Bauxsol™-based Permeable Reactive Barrier for the Treatment of Acid Rock Drainage

Permeable reactive barriers (PRBs) have generally been used to treat low flow and/or low contaminant loads of acid rock drainage (ARD). Bauxsol™, a product made from seawater-neutralized red mud (a by-product of alumina refining) buffers pH at 8.8 and has been shown to remove >99% of heavy metals loadings at >1000 meq/kg, which would make it an ideal medium for PRBs. Unfortunately, Bauxsol™ is very fine-grained (>90% of the material 90% species protection. The metal binding preference of Cu>Pb>Zn>Mn displayed by the PRB is consistent with the pKa of hydration values and it appears that MOH+ formation dominates the removal of these metals. However, other removal processes appear to apply for Fe, Al, and Cd. Overall metal removal efficiencies ranged from 91.22% for Mn to >99.99% for Cu. Analysis of dried spent Bauxsol™ indicates that bound metals are not readily leachable, allowing the spent media to be disposed safely in a landfill.

Site preference and vibrational properties of ScCu xAl 12− x

The phase stability and site preference of Cu in ScCu x Al 12− x were studied based on the pair potentials obtained by the lattice inversion method. The lattice constants of ScCu x Al 12− x with the content x were calculated and the results are in good agreement with experiment. The properties related to lattice vibration, such as the phonon density of states, specific heat and vibrational entropy, were also evaluated. The Debye and Einstein temperatures were used to characterize the acoustic branches and optic branches, respectively. In addition, several simple mechanical properties were investigated.

X-ray absorption spectroscopy study of Cu 2+ and Zn 2+ adsorption complexes at the calcite surface : Implications for site-specific metal incorporation preferences during calcite crystal growth

We report results from in situ extended X-ray absorption fine structure (EXAFS) spectroscopy studies of Cu(II) and Zn(II) complexes forming at the calcite surface following adsorption from preequilibrated calcite-saturated solutions. Both Cu(II) and Zn(II) coordinate at Ca sites on the calcite surface, forming mononuclear inner-sphere adsorption complexes. The Zn adsorption complexes are in tetrahedral coordination with first-shell O neighbors with R Zn-O = 1.95 Å, and the Cu complexes are Jahn-Teller distorted, with equatorial R Cu-O = 1.95 Å. Results from EXAFS data of dilute Cu- and Zn-calcite solid solutions confirm substitution of these metals in the Ca site of the calcite structure as octahedral complexes during coprecipitation. X-ray fluorescence microanalyses of calcite (101̄4) hillocks grown in coprecipitation experiments show that divalent Cu and Zn, which have ionic radii smaller than Ca, are preferentially incorporated into the parallel arrays of <4̄41> + steps that define one pair of symmetrically equivalent vicinal faces on polygonized growth spirals. In contrast, other divalent metals with sixfold ionic radii smaller than Ca (Co, Cd, Mn, Mg) have been shown to be preferentially incorporated into <4̄41> − growth steps, which define the second pair of vicinal faces on the growth spirals, but which are symmetrically nonequivalent to the steps on the first pair. The distortion from octahedral symmetry observed for the Cu and Zn adsorption complexes likely plays a key role in the observed preference of Cu and Zn for incorporation into the <4̄41> + steps.

Effects of some metal ions on the denaturational heat capacity increments in dilute solutions of ds-DNA

The native DNA duplex may be viewed as a cooperatively-ordered H bonded structure, including well localized Watson–Crick base pairs and H-bounded networks of hydration parts of the DNA–solvent interface in the grooves of the helix. In this paper, we present the effect of different metal ions (Li +, Mg 2+ and Cu 2+) on the denaturational heat capacity increment (Δ C p ) for calf thymus DNA. Since the contribution from the ordered hydration water fraction disruption energy to the total enthalpy and heat capacity increment values of double helix melting is significant, it must be possible to detect the effect of metal ions on the structural ordering/disordering of the H-bounded network in the hydration shell of the DNA duplex. Experimental results suggest that Li +, which is preferentially adsorbed in the minor groove of B-DNA and should contribute significantly to the stabilization of B-form, has a pronounced influence on the value of Δ C p . For the system Mg 2+–DNA, the values of Δ C p are also significant, which can be explained by the formation of inner hydration sphere complexes and immobilization of structural water by the grooves of the duplex, stabilizing the helix. The effect of Cu 2+ ions is much more pronounced. The satellite peaks of calf thymus DNA become lower as the concentration of Cu 2+ increases and for concentrations of Cu 2+ higher than 0.010 M, they disappear and Δ C p =0. This is indicative of the known preference of Cu 2+ for purins and GC rich sites of DNA, binding to the N7 of guanine. As a result, disruption of the base stacking and hydrogen bounded water networks in the grooves of the double helix takes place.

Novel chelating agents for potential clinical applications of copper

Copper offers a unique selection of radioisotopes ( 60Cu, 61Cu, 62Cu, 64Cu, and 67Cu) with half-lives ranging from 9.8 min to 61.9 h suitable for imaging and/or radiotherapy. In peptide/antibody targeted radiotherapy one of the most studied chelating agents for copper, 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA), has been employed in clinical trials, but transchelation to ceruloplasmin and/or superoxide dismutase in vivo has been noted. In this study, a series of novel hexadentate chelating agents based on N,N′,N″-tris(2-pyridylmethyl)-1,3,5- cis,cis,-triaminocyclohexane (tachpyr) have been synthesized and the serum stability of their copper complexes was evaluated as compared to TETA. Copper complexes of tachpyr modified at the 3, 4, or 5 position or with replacement of pyridine by imidazole have serum stability comparable to Cu[TETA]. When the complexes were cross-challenged, Cu[TETA] versus tachpyr or 1,3,5- cis,cis,-triaminocyclohexane- N,N′,N″-tris-(2-methyl-( N-methylimidazole)) (IM), tachpyr and IM appear to have superior copper chelation ability to TETA. When challenged by a large excess of non-radioactive copper, copper exchange with the tachpyr radio-copper complex was observed. However, tachpyr clearly exhibited a significant preference for Cu(II) over Zn(II) or Fe(III). Therefore, tachpyr, 1,3,5- cis,cis,-triaminocyclohexane- N,N′,N″-tri-(3-methyl-2-methylpyridineimine) (tachpyr(3-Me)), 1,3,5- cis,cis,-triaminocyclohexane- N,N′,N″-tri-(4-methyl-2-methylpyridineimine) (tachpyr(4-Me)), 1,3,5- cis,cis,-triaminocyclohexane- N,N′,N″-tri-(5-methyl-2-methylpyridineimine) (tachpyr(5-Me)) and IM easily form copper complexes with high stability. These novel chelating agents provide an attractive lead for creation of new copper radiopharmaceuticals for diagnosis and therapy applications.

Comparisons in the behavior of stable copper(II), silver(II), and gold(II) complexes in the gas phase: are there implications for condensed-phase chemistry?

Experiments conducted in the gas phase have led to the formation of a series of stable gold(II) complexes with nitrogen- and oxygen-containing ligands. Such complexes are very rare in condensed-phase chemistry. However, there is also a significant group of potential ligands, for example, H2O and NH3, for which stable complexes could not be formed. There are strong similarities between these observations and earlier results presented for silver(II), but both metal ions behave markedly different from copper(II). As a group the majority of successful gold(II) ligands are characterized by being good sigma donor-pi acceptor molecules; however, it is also possible to understand the ability of individual ligands to stabilize the metal ion in terms of a simple electrostatic model. Application of the latter reveals a semiquantitative trend between the physical properties of a ligand, e.g. ionization energy, dipole moment, and polarizability, and the ligand's ability to stabilize either Cu(II), Ag(II), or Au(II). The model successfully accounts for the preference of Cu(II) for aqueous chemistry, in comparison to the complete absence of such behavior on the part of Ag(II) and Au(II). Ligands from recent examples of stable condensed-phase gold(II) complexes appear to meet at least one of the criteria identified from the model.

Zinc(II) is required for the in vivo and in vitro folding of mouse copper metallothionein in two domains.

We postulate that zinc(II) is a keystone in the structure of physiological mouse copper metallothionein 1 (Cu-MT 1). Only when Zn(II) is coordinated does the structure of the in vivo- and in vitro-conformed Cu-MT species consist of two additive domains. Therefore, the functionally active forms of the mammalian Cu-MT may rely upon a two-domain structure. The in vitro behaviour of the whole protein is deduced from the Cu titration of the apo and Zn-containing forms and compared with that of the independent fragments using CD, UV-vis, ESI-MS and ICP-AES. We propose the formation of the following Cu, Zn-MT species during Zn/Cu replacement in Zn7-MT: (Zn4)alpha(Cu4Zn1)beta-MT, (Cu3Zn2)alpha(Cu4Zn1)beta-MT and (Cu4Zn1)alpha(Cu6)beta-MT. The cooperative formation of (Cu3Zn2)alpha(Cu4Zn1)beta-MT from (Zn4)alpha(Cu4Zn1)beta-MT indicates that the preference of Cu(I) for binding to the beta domain is only partial and not absolute, as otherwise accepted. Homometallic Cu-MT species have been obtained either from the apoform of MT or from Zn7-MT after total replacement of zinc. In these species, copper distribution cannot be inferred from the sum of the independent alpha and beta fragments. The in vivo synthesis of the entire MT in Cu-supplemented media has afforded Cu7Zn3-MT [(Cu3Zn2)alpha(Cu4Zn1)beta-MT], while that of alpha MT has rendered a mixture of Cu4Zn1-alpha MT (40%), Cu5Zn1-alpha MT (20%) and Cu7-alpha MT (40%). In the case of beta MT, a mixture of Cu6-beta MT (25%) and Cu7-beta MT (75%) was recovered [1]. These species correspond to some of those conformed in vitro and confirm that Zn(II) is essential for the in vivo folding of Cu-MT in a Cu-rich environment. A final significant issue is that common procedures used to obtain mammalian Cu6-beta MT from native sources may not be adequate.