Recognition and quantification of binary and ternary mixtures of isomeric peptides by the kinetic method: metal ion and ligand effects on the dissociation of metal-bound complexes

The kinetic method is applied to differentiate and quantify mixtures of isomeric tripeptides based on the competitive dissociations of divalent metal ion-bound clusters in an ion trap mass spectrometer. This methodology is extended further to determine compositions of ternary mixtures of the isomers Gly-Gly-Ala (GGA), Ala-Gly-Gly (AGG), and Gly-Ala-Gly (GAG). This procedure also allows to perform chiral quantification of a ternary mixture of optical isomers. The divalent metal ion Ca(II) is particularly appropriate for isomeric distinction and quantification of the isobaric tripeptides Gly-Gly-Leu/Gly-Gly-Ile (GGL/GGI). Among the first-row transition metal ions, Cu(II) yields remarkably effective isomeric differentiation for both the isobaric tripeptides, GGI/GGL using GAG as the reference ligand, and the positional isomers GAG/GGA using GGI as the reference ligand. This is probably due to agostic bonding: alpha-agostic bonding occurs between Cu(II) and GAG and beta-agostic bonding between Cu(II) and GGI, each produces large but different steric effects on the stability of the Cu(II)-bound dimeric clusters. These data form the basis for possible future quantitative analyses of mixtures of larger peptides such as are generated, for example, in combinatorial synthesis of peptides and peptide mimics.     

Kristall- und Molekülstruktur von Bis[N-(diethylaminothiocarbonyl)-N′-phenylbenzamidinato]kupfer(II)

Crystal and Molecular Structure of Bis[N-(diethylaminothiocarbonyl)-N′-phenyl-benzamidinato]copper(II) The structure of bis[N-(diethylaminothiocarbonyl)-N′-phenyl-benzamidinato]-copper(II) has been determined by X-ray structure analysis. The compound crystallizes in the orthorhombic space group Pbca with a = 27.792, b = 19.197, c = 12.325 Å and 8 formula units per unit cell. The structure was solved by heavy atom technique. The final R value was R = 0.06 for 1589 observed symmetry independent reflections. The coordination polyhedron is a distorted tetrahedron. In spite of the bulky phenyl groups the ligator atoms are arranged in cis position. The chelate rings deviate clearly from planarity. The phenyl rings are appreciably twisted against the chelate rings.     

Kristall- und Molekülstruktur von Bis[N-(diethylaminothiocarbonyl)-N′-phenylbenzamidinato]nickel(II)

Crystal and Molecular Structure of Bis[N-(diethylaminothiocarbonyl)-N′-phenyl-benz-amidinato]nickel(II) The structure of bis[N-(diethylaminothiocarbonyl)-N′-phenyl-benzamidinato]-nickel(II) has been determined by X-ray structure analysis. The compound crystallizes in orthorhombic space group P2₁2₁2₁ with a = 16.36, b = 16.94, c = 12.96 Å and Z = 4. The solution of the structure was performed by heavy atom technique and gave a final R value of R = 0.055 for 1764 observed reflections. The coordination polyhedron has a tetrahedrally distorted shape. The ligator atoms are arranged in cis position. The chelate rings deviate clearly from planarity. Against the chelate rings the phenyl rings are appreciably twisted. The title compound is compared regarding its structure with the analogous copper chelate.     

Crystal structures of triazine-3-thione derivatives by reaction with copper and cobalt salts

The reaction of 5-methoxy-5,6-diphenyl-4,5-dihydro-2H-[1,2,4]triazine-3-thione L1H2OCH3 with copper(II) chloride leads to the formation of an organic molecule L2 containing two triazine rings linked by a new S-S bond. A binuclear copper(II) complex, 1, containing L1 is also isolated. The reaction of L1H2OCH3 with copper(I) chloride yields a hexanuclear cluster of copper(I), 2, in which the copper atoms form a distorted octahedron with the ligand L1 acting as an NS chelate and sulfur bridge, giving to the copper ion a trigonal geometry by one N and two S atoms. In any reaction of the disulfide L2 with metal salts, complexes containing this molecule are isolated. Reactions with copper(I) and copper(II) chloride and nickel(II) and cadmium(II) nitrate produce the S-S bond cleavage, giving complexes containing the triazine L1 behaving as the NS anion, which show spectroscopic characteristics identical with those formed by reaction with L1H2OCH3. However, the reaction with cobalt(II) nitrate gives a low-spin octahedral cobalt(III) complex, in which an asymmetric rupture of the disulfide L2 has been produced, giving an unexpected complex with a new ligand and keeping the S-S bond.     

Probing the copper(II) binding features of angiogenin. Similarities and differences between a N-terminus peptide fragment and the recombinant human protein

The angiogenin protein (hAng) is a potent angiogenic factor and its cellular activities may be affected by copper ions even if it is yet unknown how this metal ion is able to produce this effect. Among the different regions of hAng potentially able to bind copper ions, the N-terminal domain appears to be an ideal candidate. Copper(II) complexes of the peptide fragments encompassing the amino acid residues 4-17 of hAng protein were characterized by potentiometric, UV-vis, CD, and EPR spectroscopic methods. The results show that these fragments have an unusual copper(II) binding ability. At physiological pH, the prevailing complex species formed by the peptide encompassing the protein sequence 4-17 is [CuHL], in which the metal ion is bound to two imidazole and two deprotonated amide nitrogen atoms disposed in a planar equatorial arrangement. Preliminary spectroscopic (UV-vis, CD, and EPR) data obtained on the copper(II) complexes formed by the whole recombinant hAng protein, show a great similarity with those obtained for the N-terminal peptide fragments. These findings indicate that within the N-terminal domain there is one of the preferred copper(II) ions anchoring site of the whole recombinant hAng protein.     

Sequence information, distinction and quantitation of C-terminal leucine and isoleucine in ternary complexes of tripeptides with Cu(II) and 2,2'-bipyridine

Tripeptides form ternary complexes with Cu(2+) and 2,2'-bipyridine (bpy) that self-assemble upon mixing the components in aqueous methanol solution. Electrospray ionization (ESI) of the complex solutions provides abundant singly charged [Cu(peptide -- H)bpy](+) and doubly charged [Cu(peptide)bpy](2+) ions. Collision-induced dissociation (CID) at low ion kinetic energies of several tripeptides, AGG, GGA, LGG, GGL, GGI, FGG, GGF, LGF, GLF, GFL, GYA and GAY, showed fragments that were indicative of the amino acid sequence in the peptide. In addition, CID of single and doubly charged complexes of isomeric tripeptides GGL and GGI provided unambiguous distinction of the isomeric leucine and isoleucine residues. Leucine peptides eliminated C(3)H(7) radicals from the amino acid side-chain whereas isoleucine eliminated C(2)H(5) radicals. CID of gas-phase doubly charged peptide complexes in a quadrupole ion trap produced a series of singly charged sequence fragments that following isolation and further CID furnished distinct fragments that allowed quantitation of leucine and isoleucine-containing peptides in mixtures.     

Kristall- und Molekülstruktur von Bis(N,N-diethyl-2-benzoylthioacetamidato)kupfer(II)

Crystal and Molecular Structure of Bis(N, N-diethyl-2-benzoylthioacetamidato)copper(II) Bis(N, N-diethyl-2-benzoyl-thioacetamidato)copper(II) has been investigated by X-ray structure analysis. It crystallizes in the triclinic space group P1 with a = 10.709, b = 12.150, c = 15.651 Å, α = 90.13, β = 103.73, γ = 98.30° and with 3 formula units per unit cell. The structure was solved by heavy atom technique. The final R value was 0.04 for 4151 symmetry independent reflections. The crystal contains two symmetry independent molecules. One of them shows a nearly planar cis-arrangement of the ligator atoms but the other has an exactly planar trans-arrangement. The chelate rings show a distorted planarity in both molecules. The results of the structure determination confirm the conclusions from the EPR crystal spectrum.     

Structural and luminescence studies of nickel(II) and copper(II) complexes with (1R,2R)-cyclohexanediamine derived unsymmetric Schiff base

Unsymmetrical Schiff base obtained by the condensation reaction of (1R,2R)(-)cyclohexanediamine with 2-hydroxybenzaldehyde and 2-hydroxynaphthaldehyde was used as a ligand for copper(II) and nickel(II). The ligand and complexes were characterized by circular dichroism (CD), UV-VIS, fluorescence, IR and (1)H (NOE diff), NOESY and (13)C NMR (ligand) spectra. The X-ray crystal structures solved for (1R,2R)(-)chxn(salH)(naftalH) and Cu(II)(1R,2R)(-)chxn(sal)(naftal) revealed tetrahedral distortion of coordination sphere in the solid phase. The [Cu(1R,2R)(-)chxn(sal)(naftal)]·0.5EtOH·1.25H(2)O complex crystallized in the monoclinic chiral C2 space group with two molecules in the asymmetric unit as well as disordered ethanol and water molecules. For both molecules Cu(II) ions were found in square-planar environments and adopts conformation described as "semi-open armed", because of distinctly oriented arms according to cyclohexane ring defined by three torsion angles. The thin layers of the ligands, copper(II) and nickel(II) complexes were deposited on Si(111) by a spin coating method and characterized with scanning electron microscopy SEM/EDS and fluorescence spectra. The ligand layers exhibit the most intensive fluorescence band at 498 nm, which can be assigned to emission transition π* → n of Schiff base ligand. For copper(II) layers the most intensive band from intraligand transition at 550 nm was observed. The highest intensity band was registered for the layer obtained when rotation speed was 1000 rpm and time 20 s. The nickel(II) complex layers fluorescence spectra exhibit an intensive band at 564 nm. The emission maxima of the copper(II) and nickel(II) complexes are shifted towards longer wavelength in comparison to the free ligand layers. CD spectra of the complexes in solution are characteristic for tetrahedral planar distortion of the chelate ring. The (1)H NMR NOE diff were measured and the position of the nearest hydrogen atoms in the cyclohexane and aromatic rings were discussed, suggesting the tetrahedral distortion of the central ion of the coordination sphere in solution.     

Cobalt(III), nickel(II), and copper(II) complexes of 1-thia (or oxa)4,7-diazacyclononane and related mixed-ligand cobalt(III) complexes

Summary To investigate the effect of substitution of an oxygen or a sulphur donor atom for a nitrogen donor atom in a cyclic triamine, 1,4,7-triazacyclononane (tacn), cobalt(III), nickel(II), and copper(II) complexes of 1-oxa-4,7-diazacyclononane (taon) and 1-thia-4,7-diazacyclononane (tasn), and related mixed ligand cobalt(III) complexes were prepared and characterized. The coordination ability of an ether-oxygen or a thioether-sulphur atom increases when these atoms are incorporated into cyclic terdentate ligands. Electronic spectra reveal that ligand field strengths of these atoms are enhanced significantly. The presence of these heteroatoms affects circular dichroism spectra because of the increased flexibility of the chelate rings.     

Kristall- und Molekülstruktur von N,N′-o-Phenylen-bis-(N″,N′-diethyl-N‴-benzimidoyl-thioureato)nickel(II)

Crystal and Molecular Structure of N,N′-o-Phenylen-bis-(N″,N″-diethyl-N?-benzimidoyl-thioureato)nickel(II) The structure of the title compound has been determined by an X-ray structure analysis. The compound crystallizes in the monoclinic space group C2/c with a = 38.896, b = 14.326, c = 11.121 Å, β = 102.33° and Z = 8. The solution of the structure was performed by Patterson methods. The final R value was R = 0.053 for 2260 observed reflections. The coordination geometry is nearly planar. The ligator atoms show as a necessity a cis arrangement. The chelate rings deviate from planarity. The phenyl rings and the phenylene fragment are significantly twisted in respect to the chelate rings.     

Quantum-chemical calculation of molecular structures of (5656)macrotetracyclic 3d-metal complexes “self-assembled” in quaternary systems M(II) ion-ethanedithioamide-formaldehyde-ammonia by the density functional theory method

The geometric parameters of (5656)macrotetracyclic complexes of Mn(II), Fe(II), Co(II), Ni(II), Cu(II), and Zn(II) with the NNNN-coordination of donor sites of the chelant formed by the template reactions in the M(II)-ethanedithioamide-formaldehyde-ammonia systems have been calculated by the OPBE/TZVP hybrid density functional theory (DFT) method with the use of the Gaussian09 program package. In all complexes, five-membered chelate rings (almost identical to each other in each complex) are nonplanar. For all M(II) ions under consideration, two additional six-membered nonplanar chelate rings formed as a result of template “cross-link” are turned at considerable angles with respect to the five-membered rings. The six-membered rings are located on different sides of the NNNN plane of the nitrogen donor atoms.     

Relationship between Coordination Structure and Biological Activity of Copper(II) Nicotinate

1 INTRODUCTION In 1945, Braude[1] found for the first time that adding copper (Cu) ten times the normal requisite amount into the feed can improve the production property of the animal obviously. Therefore, from then on copper has been widely applied in pig- breeding industry as an effective growth-promoting agent, especially in the process of intensive culture, which plays an important part in improving the growth of animal and the production property. However, at the same time, the high…     

Trinuclear copper(II) complexes with diacylhydrazines of aliphatic dicarboxylic acids and salicylic acid

Trinuclear copper(II) complexes with diacyldihydrazines of aliphatic dicarboxylic acids (from succinic acid to heptadioic acid) and salicylic acid were synthesized. The complexes were studied by chemical analysis, thermogravimetry, and IR spectroscopy. The structure of trinuclear copper(II) complex with diacylhydrazine of glutaric and salicylic acids of the [Cu₃L³ · 4Py] · 2Py composition was determined by X-ray crystallography. The complex has a molecular structure and contains three nonequivalent copper atoms. The Cu(2)...Cu(3) distance is 8.506 Å; the Cu(2)...Cu(1) and Cu(3)...Cu(1) distances are 4.612 and 4.588 Å, respectively. The coordination polyhedra of two copper atoms are tetragonal pyramids, and the third copper atom has a square environment. An interest feature of the complex under study is the induced closure of the bent eight-membered chelate ring containing carbon atoms of a polymethylene spacer.     

OBSERVATIONS ON THE CONFORMATION OF IMINODIACETATE(2-) ION IN MIXED LIGAND COPPER(II) COMPLEXES WITH NITROGEN HETEROCYCLES AS SECONDARY LIGANDS. CRYSTAL STRUCTURE OF (2,2′-BYPIRIDINE)(IMINODIACETATO)COPPER(II) HEXAHYDRATE

Abstract

(2,2′-Bipyridine)(iminodiacetato)copper(II) hexahydrate, [Cu(IDA)(2,2′-bipy)]·6H₂O, has been obtained and studied by X-ray diffraction. The compound (triclinic system, space group P1, Z = 2; R = 0.036 and R = 0.040 for 7541 independent reflections) consists of asymmetric dinuclear entities, [Cu(IDA)(2,2′-bipy)]₂, and uncoordinated H₂O molecules in a hydrogen bonding network. Both Cu(II) atoms of each dinuclear entity are chemically very similar. Each Cu(II) atom exhibits a flattened, square pyramidal coordination. Two N atoms of 2,2′-bipy and the N and one O atoms of IDA are at the square base; another O atom of the same terdentate IDA is at the apical position. Two weak interactions between each Cu(II) atom and one O atom from IDA which chelates the second contribute to the dinuclear entity. On the basis of these results and the known structure of other Cu(II) complexes with IDA and imidazole or 4,4′-bipy, an attempt to rationalize the nearly coplanar or perpendicular conformation of the two five-membered IDA-Cu(II) chelate rings in such mixed-ligand copper(II) complexes is made.     

Asymmetric sulfur atom coordination in a copper(II) dipicolylamine (DPA) complex with a thioglycoside ligand

The 2,2'-dipicolylamine (DPA)-tethered thioglycoside ligand, N,N-bis(2-pyridylmethyl)-2-aminoethyl 1-deoxy-1-thio-2,3,4,6-tetra-O-acetyl-beta-d-glucopyranoside (sL1), has been prepared and its copper(II) complex synthesized. Using copper(II) chloride, the copper complex was isolated as a chloride-bound species formulated as [Cu(sL1)Cl(ClO(4))](1). The corresponding O-glycoside complex ([Cu(L1)Cl](ClO(4)), 2) was also prepared using L1 (N,N-bis(2-pyridylmethyl)-2-aminoethyl 2,3,4,6-tetra-O-acetyl-beta-d-glucopyranoside), and both complexes were characterized and compared by means of X-ray crystallography, cyclic voltammetry, electronic absorption and circular dichroism (CD) spectra. Although both complexes exhibited similar copper coordination geometries, the absolute configuration of the O/S chiral center generated by the copper coordination was inverted. The electronic and CD spectra of acetonitrile solutions of 1 and 2 were different likely due to the presence of a copper-sulfur charge-transfer band for 1. Complex also exhibits a large Cotton effect around 700 nm. The corresponding d-d transition of the copper(II) center reveals that the asymmetric copper-sulfur (oxygen) coordination remains even in solution.     

Trigonal planar copper(I) complex: synthesis, structure, and spectra of a redox pair of novel copper(II/I) complexes of tridentate bis(benzimidazol-2'-yl) ligand framework as models for electron-transfer copper proteins

The copper(II) and copper(I) complexes of the chelating ligands 2,6-bis(benzimidazol-2'-ylthiomethyl)pyridine (bbtmp) and N,N-bis(benzimidazol-2'-ylthioethyl)methylamine (bbtma) have been isolated and characterized by electronic and EPR spectra. The molecular structures of a redox pair of Cu(II/I) complexes, viz., [Cu(bbtmp)(NO(3))]NO(3), 1, and [Cu(bbtmp)]NO(3), 2, and of [Cu(bbtmp)Cl], 3, have been determined by single-crystal X-ray crystallography. The cation of the green complex [Cu(bbtmp)(NO(3))]NO(3) possesses an almost perfectly square planar coordination geometry in which the corners are occupied by the pyridine and two benzimidazole nitrogen atoms of the bbtmp ligand and an oxygen atom of the nitrate ion. The light-yellow complex [Cu(bbtmp)]NO(3) contains copper(I) with trigonal planar coordination geometry constituted by the pyridine and two benzimidazole nitrogen atoms of the bbtmp ligand. In the yellow chloride complex [Cu(bbtmp)Cl] the asymmetric unit consists of two complex molecules that are crystallographically independent. The coordination geometry of copper(I) in these molecules, in contrast to the nitrate, is tetrahedral, with pyridine and two benzimidazole nitrogen atoms of bbtmp ligand and the chloride ion occupying the apexes. The above coordination structures are unusual in that the thioether sulfurs are not engaged in coordination and the presence of two seven-membered chelate rings facilitates strong coordination of the benzimidazole nitrogens and discourage any distortion in Cu(II) coordination geometry. The solid-state coordination geometries are retained even in solution, as revealed by electronic, EPR, and (1)H NMR spectra. The electrochemical behavior of the present and other similar CuN(3) complexes has been examined, and the thermodynamic aspects of the electrode process are correlated to the stereochemical reorganizations accompanying the redox changes. The influence of coordinated pyridine and amine nitrogen atoms on the spectral and electrochemical properties has been discussed.     

铜(II)/明胶(酶解明胶)络合物的制备及其络合形态的探讨

许多金属元素对于生物体是必需的,Ｎａ、Ｋ、Ｍｇ、Ｃａ、Ｍｎ、Ｆｅ、Ｃｏ、Ｃｕ、Ｍｏ和Ｚｎ在人体中的含量约３％;各种金属离子在生物体中具有不同的作用,其功能是很复杂的．铜在生物体内主要是进行氧化还原反应,起输送氧气和电子载体的作用．如果人体内缺乏铜,则...     

Acetylacetonate bis(thiosemicarbazone) complexes of copper and nickel: towards new copper radiopharmaceuticals

A series of copper(II) and nickel(II) 1,3-bis(thiosemicarbazonato) complexes have been synthesised by the reaction of the metal acetates with pyrazoline proligands. In each case the complexes have an overall neutral charge with a dianionic ligand. The copper 1,3-bis(4-methyl-3-thiosemicarbazonato complex has been characterised by X-ray crystallography, which shows the copper is in an essentially square-planar symmetric N(2)S(2) environment. The nickel 1,3-bis(4-methyl-3-thiosemicarbazonato) and nickel 1,3-bis(4-phenyl-3-thiosemicarbazonato) complexes have been characterised by X-ray crystallography and show that in these cases the nickel is in a distorted square-planar environment, but the bonding mode of the ligands is unusual; the nickel binds to one of the aza-methinic nitrogen atoms and one hydrazinic nitrogen, creating one five-membered N-N-C-S-Ni chelate ring and one four-membered N-C-S-Ni chelate ring. Interestingly, the X-ray structure of the ethyl analogue [1,3-bis(4-ethyl-3-thiosemicarbazonato)nickel(II)] shows that in this case the nickel is symmetrically coordinated in the usual manner. The nickel complexes are diamagnetic and the different coordination modes are confirmed in solution by NMR spectroscopy. The complexes are susceptible to oxidation in air and a nickel complex, in which the central methylene carbon has been oxidised, has been characterised by X-ray crystallography and NMR spectroscopy. Electrochemical measurements show that the copper complexes undergo a reversible one-electron reduction at biologically accessible potentials.     

Copper(II) binding by fragments of alpha-synuclein containing M1-D2- and -H50-residues; a combined potentiometric and spectroscopic study

Stability constants and ligand donor sets of the copper(II) complexes of the NH2-29-56(L1)(AA30GKTKEGVLYV40GSKTKEGVVH50GVATVA56-NH2), NH2-M29-D30-56(L2) and Ac-M29-D30-56(L3) fragments of alpha-synuclein were determined in aqueous solution for 1 : 1 metal-to-ligand molar ratio in the pH range 2.5-10.5. The tyrosine residue in the 39th position of the alpha-synuclein fragments does not take part in the coordination of the metal ion. The potentiometric and spectroscopic data (UV-Vis, CD, EPR) show that acetylation of the amino terminal group induces significant changes in the coordination properties of the L3 fragment compared to that of the L2 peptide. When the amino group is blocked (L3) the imidazole nitrogen of the histidine residue acts as an anchoring site and at higher pH the 3N {N(Im),2N-} and 4N {N(Im),3N-} complexes are formed. The L1 peptide at physiological pH forms in equilibrium 3N {NH2,N-,CO,N(Im)} and 4N {NH2,2N-,N(Im)} complexes. For the L2 peptide the coordination of the copper(II) ions starts from the N-terminal Met residue and with increasing of pH the Asp residue in second position of amino acid sequence coordinates and stabilizes significantly the 2N complex as a result of chelation through the beta-carboxylate group. At physiological pH the 3N {NH2,N-,beta-COO-,N(Im)} coordination mode dominates. At pH above 6 the results for the L2 fragment suggest the formation of 3N and 4N complexes (in equatorial plane) and the involvement of the lateral NH2 group of Lys residue in the axial coordination of Cu(II) ion. In CD spectra sigma (epsilon-NH2-Lys) --> Cu(II) charge transfer transition is observed. The stability constants for the L2 fragment of alpha-synuclein of the 4N {NH2,2N-,N(Im)} and {NH2,3N-} complexes are higher about 1.5 and 0.7 orders of magnitude, respectively, by comparison to those of the L1 peptide. This increase may be explained by the involvement of the epsilon-NH2 group of Lys residue in the coordination sphere of metal ion.     

Copper(II) binding modes in the prion octapeptide PHGGGWGQ: a spectroscopic and voltammetric study

The N-terminal octapeptide repeat region of human prion protein (PrPc) is known to bind Cu(II). To investigate the binding modes of copper in PrPc, an octapeptide Ac-PHGGGWGQ-NH2 (1), which corresponds to an octa-repeat sequence, and a tetrapeptide Ac-HGGG-NH2 (2) have been synthesised. The copper(II) complexes formed with 1 and 2 have been studied by circular dichroism (CD) and electron spin resonance (ESR) spectroscopy. Both peptides form 1:1 complexes with Cu(II) at neutral and basic pH. CD, ESR and visible absorption spectra suggest a similar co-ordination sphere of the metal ion in both peptides, which at neutral pH consists of a square pyramidal geometry with three peptidic nitrogens and the imidazole nitrogen as donor atoms. Cyclic voltammetric measurements were used to confirm the geometrical features of these copper(II) complexes: the observation of negative redox potentials are in good agreement with the inferred geometry. All these results taken together suggest that peptide 1 provides a single metal binding site to which copper(II) binds strongly at neutral and basic pH and that the binding of the metal induces the formation of a stiffened structure in the HGGG peptide fragment.