Formation and spectral properties of metal ion complexes of tripeptides (original) (raw)
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Inorganics, 2022
Copper(II) complexes of glycyl-L-leucyl-L-histidine (GLH), sarcosyl-L-leucyl-L-histidine (Sar-LH), glycyl-L-phenylalanyl-L-histidine (GFH) and sarcosyl-L-phenylalanyl-L-histidine (Sar-FH) have potential anti-inflammatory activity, which can help to alleviate the symptoms associated with rheumatoid arthritis (RA). From pH 2–11, the MLH, ML, MLH-1 and MLH-2 species formed. The combination of species for each ligand was different, except at the physiological pH, where CuLH-2 predominated for all ligands. The prevalence of this species was supported by EPR, ultraviolet-visible spectrophotometry, and mass spectrometry, which suggested a square planar CuN4 coordination. All ligands have the same basicity for the amine and imidazole-N, but the methyl group of sarcosine decreased the stability of MLH and MLH-2 by 0.1–0.34 and 0.46–0.48 log units, respectively. Phenylalanine increased the stability of MLH and MLH-2 by 0.05–0.29 and 1.19–1.21 log units, respectively. For all ligands, 1H NMR i...
Stability, solution structure and X-ray crystallography of a copper (II) diamide complex
Inorganica Chimica Acta 498 (2019) , 2019
It has been shown that the inflammation associated with rheumatoid arthritis can be reduced using copper complexes. In order to improve the bioavailability of copper and hence efficacy, 3-(2-aminoacetamido)-N-(pyridin-2-ylmethyl)propanamide, H2(5 6 5)NH2, was designed as a potential chelator of copper. Solution equilibrium measurements show that the [Cu(LH-2)] species predominates at physiological pH and blood plasma speciation calculations predict that this ligand is able to mobilise Cu(II) in vivo. A structural study of the Cu(II)/H2(5 6 5)NH2 system was conducted in the solid and solution state using Uv–Vis, CD, 1H NMR and EPR spectroscopy and single crystal X-ray crystallography. The result indicate that the structure of [Cu(H2(5 6 5)NH2)H-2] in the solid and solution state are similar and confirm that, the metal binds to the pyridine nitrogen, the two amide nitrogens and the terminal amino group in a distorted square planar geometry.
Journal of Inorganic Biochemistry, 2007
The systematic investigation of the copper(II) complexes of tripeptides Xaa-Xaa-His, Xaa-His-Xaa and His-Xaa-Xaa, where Xaa = Gly or Ala was performed by combined pH-metry, spectrophotometry, CD and in part EPR spectroscopy. The matrix rank analysis of the spectral data revealed the number of the coloured and optically active species as a basis for the solution speciation. A critical evaluation on the speciation and solution structure of the complexes formed is presented on the basis of their d-d band optical activity. The replacement of a Gly residue with the chiral Ala amino acid allowed us to gain decisive information on the solution structure of the complexes by CD spectroscopy. It was shown that the tripeptides with histidine in the third position formed CuH À2 L species with (NH 2 , 2N À , ImN-where Im stands for imidazole) coordination sphere as a major species, and only the macrochelated CuL complexes as minor species around pH 5.0. In copper(II)-Xaa-His-Xaa tripeptide systems the CuH À1 L (NH 2 , N À , ImN) is the most stable species at physiological pH, but the vacant fourth site around copper(II)ions is offered for further deprotonation, most probably resulting in mixed hydroxo species at low (<5 • 10 À4 M) metal ion concentrations, while a tetrameric complex is dominant when the copper concentration exceeds 3 • 10 À3 M. The histamine type coordination mode in CuL and CuL 2 complexes of His-Xaa-Xaa ligands predominates at low pH. The structural consequences drawn from the CD spectra for the mono and bis parent complexes were supported by theoretical calculations. CD spectra strongly suggest the participation of the imidazole nitrogen both in the Cu 2 H À2 L 2 and CuH À2 L complexes.
Zenodo (CERN European Organization for Nuclear Research), 2003
In order to obtain new potential antioxidants with molecular mass lower than those of the metal-proteins, a new copper(II) compound with mixed ligands, L-histidine and urea was synthesised. The compounds containing only one of the two mentioned ligands, Cu-urea and Cu-L-histidine was also synthesised as intermediates in the synthesis of the compound with mixed ligands or for comparative purposes. The spectral analysis indicates an axial symmetry of the Cu 11 ions in the compound with mixed ligands. Stability studies, in time and in different Jill-conditions, were carried out by absorption electronic spectroscopy; the results revealed satisfactory stability in time, at the pH of the physiologic serum of the compounds with mixed ligands; the compound is also stable in aqueous solutions at pH 7.2-5.5. The study of compatibility with physiological mediums indicates that the compound displays significant lypophilic character.
Journal of Inorganic Biochemistry, 2009
CD and EPR were used to characterize interactions of oxindole-Schiff base copper(II) complexes with human serum albumin (HSA). These imine ligands form very stable complexes with copper, and can efficiently compete for this metal ion towards the specific N-terminal binding site of the protein, consisting of the amino acid sequence Asp-Ala-His. Relative stability constants for the corresponding complexes were estimated from CD data, using the protein as competitive ligand, with values of log K CuL in the range 15.7-18.1, very close to that of [Cu(HSA)] itself, with log K CuHSA 16.2. Some of the complexes are also able to interfere in the a-helix structure of the protein, while others seem not to affect it. EPR spectra corroborate those results, indicating at least two different metal species in solution, depending on the imine ligand. Oxidative damage to the protein after incubation with these copper(II) complexes, particularly in the presence of hydrogen peroxide, was monitored by carbonyl groups formation, and was observed to be more severe when conformational features of the protein were modified. Complementary EPR spin-trapping data indicated significant formation of hydroxyl and carbon centered radicals, consistent with an oxidative mechanism. Theoretical calculations at density functional theory (DFT) level were employed to evaluate Cu(II)-L binding energies, L ? Cu(II) donation, and Cu(II) ? L back-donation, by considering the Schiff bases and the N-terminal site of HSA as ligands. These results complement previous studies on cytotoxicity, nuclease and pro-apoptotic properties of this kind of copper(II) complexes, providing additional information about their possibilities of transport and disposition in blood plasma.
Canadian Journal of …, 2009
The structures and relative free energies in aqueous solution of the Cu(II) complexes of the ''histidine walk'' peptides, AcHGGGNH2, AcGHGGNH2, AcGGHGNH2, and AcGGGHNH2, were determined as a function of pH. Numerous structures of each species were found by gaseous-and solution-phase geometry optimization at the B3LYP/6-31G(d) level, and the effect of solvation estimated by the IEFPCM continuum solvation model. Free energies of solvation of the ionic species are large and favour structures with an extended peptide chain. In all Cu(II)-peptide complexes, deprotonation of two amide groups occurs readily at or below pH 7. In each system, the most abundant species at pH 7 is a neutral 1:1 complex with N3O1 coordination pattern. Binding in the forward direction toward the C terminus is preferred. The results are compared to recent experimental spectroscopic and potentiometric studies on related systems. Alternative explanations are offered for some of the experimental observations. Résumé : On a déterminé les structures et les énergies libres, en solutions aqueuses et en fonction du pH, des complexes de Cu(II) des peptides de la série histidine, AcHGGGNH 2 , ACGHGGNH 2 , AcGGHGNH 2 et ACGGGHNH 2 . On a déterminé les diverses structures de chacune des espèces, en phase gazeuse et en solution, par une optimisation de la géométrie au niveau B3LYP/6-31G(d) et on a évalué l'effet de solvatation par le modèle de solvatation continue IEEPCM. Les énergies libres de solvatation des espèces ioniques sont importantes et elles favorisent les structures avec une chaîne peptidique étendue. Dans tous les complexes Cu(II)-peptide, la déprotonation de deux groupes amides se produit facilement à des pH égal ou inférieurs à 7. Dans chaque système, l'espèce la plus abondante au pH 7 est un complexe 1:1 neutre comportant un patron de coordination N3O1. La fixation est favorisée dans la direction allant vers la position C-terminale. On compare les résultats obtenus ici avec ceux rapportés récemment pour des études expérimentales spectroscopiques et potentiométriques sur des systèmes apparentés. Des explications alternatives sont proposées pour un certain nombre d'observations expérimentales.
Copper(II)–l-glutamine complexation study in solid state and in aqueous solution
Inorganica Chimica Acta, 2003
Among copper transport alterations in humans, Menkes disease is due to a lethal genetic disorder. The current treatment is the administration of physiological Cu(II) Á/L-histidine complex. However, this therapy is only effective in some cases and when started early in life. In order to distribute copper in all the biological compartments for Menkes disease patients, the administration of other Cu(II) amino acids complexes has been considered. Several ternary Cu(II) Á/amino acids complexes were detected in human serum playing an important role in the copper pathway, in particular L-histidine Á/Cu(II) Á/L-glutamine. Before the biopharmaceutical studies of L-histidine Á/Cu(II) Á/L-glutamine complex, a physicochemical characterisation of binary Cu(II) Á/L-glutamine complex must be conducted. Indeed, the identification of Cu(II) Á/L-glutamine species has not been clearly determined at physiological pH in the past. In the present work, the stoichiometry, formation constants and distribution of the various Cu(II) Á/L-glutamine species have been determined by polarography and UV Á/Vis spectroscopy in a large pH range. [Cu(II)(Gln) 2 ] complex is the major component at physiological pH and its formation constant is equal to 10 12.5 l 2 mol (2 . For the first time, the structure of [Cu(II)(Gln) 2 ] has been determined in the solid state and in solution. Given the small size of the obtained crystals, it has been necessary to use an X-ray synchrotron source to collect the diffraction data. X-ray crystal structure showed a 4-2 distorted octahedral geometry. In the basal plane Cu Á/O and Cu Á/N distances ranged from 1.93 to 1.98 Å . Two additional oxygen atoms at 2.70 and 2.86 Å complete a severely distorted octahedron. EXAFS and EPR results have shown that the structure of [Cu(II)(Gln) 2 ] is preserved at physiological pH in aqueous solution. #
Copper Cation Interactions with Biologically Essential Types of Ligands: A Computational DFT Study
The Journal of Physical Chemistry A, 2006
This work presents a systematic theoretical study on Cu(I) and Cu(II) cations in variable hydrogen sulfideaqua-ammine ligand fields. These ligands model the biologically most common environment for Cu ions. Molecular structures of the complexes were optimized at the density functional theory (DFT) level. Subsequent thorough energy analyses revealed the following trends: (i) The ammine complexes are the most stable, followed by those containing the aqua and hydrogen sulfide ligands, which are characterized by similar stabilization energies. (ii) The most preferred Cu(I) coordination number is 2 in ammine or aqua ligand fields. A qualitatively different binding picture was obtained for complexes with H 2 S ligands where the 4-coordination is favored. (iii) The 4-and 5-coordinated structures belong to the most stable complexes for Cu(II), regardless of the ligand types. Vertical and adiabatic ionization potentials of Cu(I) complexes were calculated. Charge distribution (using the natural population analysis (NPA) method) and molecular orbital analyses were performed to elucidate the nature of bonding in the examined systems. The results provide in-depth insight into the Cu-binding properties and can be, among others, used for the calibration of bioinorganic force fields.