Copper(II) complexes of peptide-group-containing amino acids bis(N-acetyl-l-alaninate)copper(II) complexes and their amine adducts

The bis(N-acetyl-l-alanine)copper(II) monohydrate for which magnetic data and electronic and IR spectra suggest a copper-acetate monohydrate type structure, was prepared. Substitution of the water molecule by some amines was made to investigate their effect on the amino acid coordination and on the geometry around the copper ion. For the adducts of monodentate heterocyclic amines such as N-methylpiperazine, piperidine, morpholine, pyridine, 3- and 4-methylpyridine (CuL₂B₂) and of bidentate amines such as piperazine, ethylenediamine, 2,2′- and 4,4′-bipyridine (CuL₂B) in the solid state or chloroform solution, magnetism, electronic spectra (one d-d band in the 14,500–18,700 cm⁻¹ spectral region, depending on the bascity or steric interference of the amines) and IR spectra suggest a square-planar or strongly distorted tetragonal arrangement around the copper ion with a CuN₂O₂ or CuN₄ chromophore. For the Cu(N-acll-ala)₂B₂ (B  N-methylpiperazine, piperidine and morpholine) adducts in chloroform solution in the presence of excess amine, electronic (two d-d bands) and IR spectra indicate tetragonal arrangement around the copper ion with CuN₄O₂ chromophore, while for the Cu(N-ac-l-ala)₂ · o-phen adduct in the solid state and chloroform solution they suggest the presence of 6-coordinate cis-octahedral species, with CuN₂O₄ chromophores. In all the adducts studied the IR spectra exclude any interaction between the peptide group and the metal ion.     

Hydration of copper(II) amino acids complexes

Hydration of the copper(II) bis‐complexes with glycine, serine, lysine, and aspartic acid was studied by DFT and MD simulation methods. The distances between copper(II) and water molecules in the 1st and 2nd coordination shells, the average number of water molecules and their mean residence times in the hydration shells were calculated. Good agreement was observed between the values obtained and those found by DFT and NMR relaxation methods. Influence of the functional groups of the ligands and the cis–trans isomerism of the complexes on the structural and dynamical parameters of the hydration shells was displayed and explained. Analysis of the MD trajectories reveals the competition for a copper(II) axial position between water molecules or water molecules and the functional chain groups of the ligands and confirms the suggestion on the pentacoordination of copper(II) in such complexes. MD simulations show that only one axial position of Cu(II) is basically occupied at each time step while in average the coordination number more than 5 is observed. © 2017 Wiley Periodicals, Inc.     

Diaza-crown-N,N-dialkanoic acids copper(II) and dicopper(II) complexes

Twelve-, fifteen-, and eighteen-membered diaza-crown-N, N-′dialkanoic acids LH₂ and their inner salt copper(II) complexes CuL and dicopper complex [CuL(3). CuCl₂. CH₃OH_n were obtained. The complexes of 15- and 18-membered ligands contain Cu²⁺ ion inside the ring.     

Structure-activity relationships of highly cytotoxic copper(II) complexes with modified indolo[3,2-c]quinoline ligands

A number of indolo[3,2-c]quinolines were synthesized and modified at the lactam unit to provide a peripheral binding site able to accommodate metal ions. Potentially tridentate ligands HL(1a)-HL(4a) and HL(1b)-HL(4b) were reacted with copper(II) chloride in isopropanol/methanol to give novel five-coordinate copper(II) complexes [Cu(HL(1a-4a))Cl(2)] and [Cu(HL(1b-4b))Cl(2)]. In addition, a new complex [Cu(HL(5b))Cl(2)] and two previously reported compounds [Cu(HL(6a))Cl(2)] and [Cu(HL(6b))Cl(2)] with modified paullone ligands HL(5b), HL(6a), and HL(6b), which can be regarded as close analogues of indoloquinolines HL(1b), HL(4a), and HL(4b), in which the pyridine ring was formally substituted by a seven-membered azepine ring, were synthesized for comparison. The new ligands and copper(II) complexes were characterized by (1)H and (13)C NMR, IR and electronic absorption spectroscopy, ESI mass spectrometry, magnetic susceptibility measurements in solution at 298 K ([Cu(HL(1a))Cl(2)] and [Cu(HL(4b))Cl(2)]), and X-ray crystallography ([Cu(HL(3b))Cl(2)]·3DMF, [Cu(HL(4b))Cl(2)]·2.4DMF, HL(5b) and [Cu(HL(5b))Cl(2)]·0.5CH(3)OH). All complexes were tested for cytotoxicity in the human cancer cell lines CH1 (ovarian carcinoma), A549 (non-small cell lung cancer), and SW480 (colon carcinoma). The compounds are highly cytotoxic, with IC(50) values ranging from nanomolar to very low micromolar concentrations. Substitution of the seven-membered azepine ring in paullones by a pyridine ring resulted in a six- to nine-fold increase of cytotoxicity in SW480 cells. Electron-releasing or electron-withdrawing substituents in position 8 of the indoloquinoline backbone do not exert any effect on cytotoxicity of copper(II) complexes, whereas copper(II) compounds with Schiff bases obtained from 2-acetylpyridine and indoloquinoline hydrazines are 10 to 50 times more cytotoxic than those with ligands prepared from 2-formylpyridine and indoloquinoline hydrazines.     

Ternary mixed-ligand copper(II) complexes with chiral aminophosphonic acids and amino acids

Ternary mixed-ligand complexes of divalent copper, where one ligand is an -aminoalkylphosphonic acid (APA) and the second ligand is L-phenylalanine, L-tyrosine, or L-dihydroxyphenylalanine, are studied by potentiometric titration in aqueous medium at 25°C and =0.1. A maximum in the formation of the ternary complexes is exhibited at pH 7–8. The log K_st for the complexes formed and the statistical parameters characterizing the ternary complexes logK and logX are determined. The effect of substituents on the -carbon atom of the -APA and of hydroxy groups on the phenyl substituent of the -amino acids on the nature of the distribution of the complexes formed is studied.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2482–2486, November 1989.The authors thank V. P. Solov'ev for helpful discussions.     

The reaction of 2-aminomethylphenols and their copper(II) complexes with esters of phosphorus acids

2-Alkyl- and 2-dialkylaminomethylphenols (AMP) with different hydrophobic substituents at the nitrogen atom and their copper(II) complexes (CAMP) react with the esters of phosphorus acids in aqueous solutions of ethanol in two stages: phosphorylated AMP (PAMP) are formed at the first stage and then hydrolyzed to the corresponding acids. The reactivity of AMP and PAMP significantly decreases when the hydrophobicity and steric hindrances of substituents at the nitrogen atom increase. An inverse dependence was found for CAMP. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1355–1360, August, 2000.     

Neutral pyridylmethylamide ligands and their mononuclear copper(II) complexes

Mononuclear copper(II) complexes of a family of pyridylmethylamide ligands HL, HL^Me, HL^Ph, HL^Me3 and HL^Ph3, [HL = N-(2-pyridylmethyl)acetamide; HL^Me = N-(2-pyridylmethyl)propionamide; HL^Ph = 2-phenyl-N-(2-pyridylmethyl)acetamide; HL^Me3 = 2,2-dimethyl-N-(2-pyridylmethyl)propionamide; HL^Ph3 = 2,2,2-triphenyl-N-(2-pyridylmethyl)acetamide], were synthesized and characterized. The reaction of copper(II) salts with the pyridylmethylamide ligands yields complexes [Cu(HL)₂(OTf)₂] (1), [Cu(HL^Me)₂](ClO₄)₂ (2), [Cu(HL)₂Cl]₂[CuCl₄] (3), [Cu(HL^Me3)₂(THF)](OTf)₂ (4), [Cu(HL^Me3)₂(H₂O)](ClO₄)₂ (5a and 5b), [Cu(HL^Ph3)₂(H₂O)](ClO₄)₂ (6), [Cu(HL)(2,2′-bipy)(H₂O)](ClO₄)₂ (7), and [Cu(HL^Ph)(2,2′-bipy)(H₂O)](ClO₄)₂ (8). All complexes were fully characterized, and the X-ray structures vary from four-coordinate square-planar, to five-coordinate square-pyramidal or trigonal-bipyramidal. The neutral ligands coordinate via the pyridyl N atom and carbonyl O atom in a bidentate fashion. The spectroscopic properties are typical of mononuclear copper(II) species with similar ligand sets, and are consistent their X-ray structures.     

Thermal studies on nickel(II) and copper(II) complexes of monoethanol- and diethanol-dithiocarbamic acids

Thermoanalytical data (TG/DTA) have been obtained for bis-monoethanoldithiocarbamato nickel(II) and bis-diethanoldithiocarbamato nickel(II) and copper(II) complexes. A thermal decomposition mechanism is proposed for bis-monoethanoldithiocarbamato nickel(II).     

Investigation of ketoconazole copper(II) and cobalt(II) complexes and their spectrophotometric applications

Ketoconazole, as a ligand, reacts quantitatively with copper(II) and cobalt(II) to form blue-colored, stable complexes in dichloromethane. These complexes can be spectrophotometrically measured at 720 and 612.5 nm in the case of Cu(II) or Co(II), respectively. Different factors affecting the reaction such as pH, reagent concentration, solvent effect, and time were studied. By using Job's method of continuous variation, the stoichiometry of the reaction was found to be in the ratio of 1:2, metal:drug, with Cu(II) and Co(II). The stability of the complexes formed was also studied. The reaction products were isolated for further investigation. The complexes have apparent molar absorptivities of 35.36 +/- 1.95 and 59.62 +/- 1.87 for Cu(II) and Co(II), respectively. Suggested procedures based on the stoichiometric reaction were successfully applied to the analysis of the pure drug and its pharmaceutical formulations. The validity of the procedures was further ascertained by the method of standard additions. The developed method was found to be simple, accurate, and precise when compared with the official method of the British Pharmacopoeia.     

Nickel(II) and copper(II) complexes with humic acid anions and their derivatives

Complexation of Ni(II) and Cu(II) in aqueous solutions with anions of humic acids, extracted from naturally oxidized coal, and with their hydroxymethyl derivatives is studied spectrophotometrically and potentiometrically. The complexation stoichiometry and the stability constants of the complexes are determined.     

Mixed ligand complexes of copper(II) involving amino acids and peptides

Summary The formation and stability of the mixed-ligand complexes of copper(II) with diethylenetriamine (dien) and amino acids or peptides have been investigated by potentiometric and conductometric techniques. The results indicate that the apical coordination of the ionized amide group of the peptide and the ionized alcoholatogroup of the amino acid is not possible.     

Magneto-structural relationships in a series of dinuclear oxalato-bridged (diphenyldipyrazolylmethane)copper(II) complexes

A series of oxalato-bridged dinuclear copper(II) complexes of the general formula [Cu2(Pz2CPh2)2(X)2(mu-C2O4)] (X = Cl- (1), NO3(-) (2), ClO4(-) (3); Pz2CPh2 = diphenyldipyrazolylmethane) or [Cu2(Pz(3m)2CPh2)2(H2O)2(mu-C2O4)](NO3)2 x H2O (4) (Pz(3m)2CPh2 = diphenylbis(3-methylpyrazolyl)methane) was synthesized where the axial ligand was systematically varied to study its effect on structure and magnetic coupling. The structures of compounds 1, 2, and 4 have been elucidated by single-crystal X-ray diffraction. [Cu2(Pz2CPh2)2(Cl)2(mu-C2O4)] and [Cu2(Pz2CPh2)2(NO3)2(mu-C2O4)] are isostructural and crystallize in the triclinic system, space group P, Z = 2, with a = 8.6155(8) A, b = 10.1435(9) A, c = 11.3612(11) A, alpha = 95.535(2) degrees, beta = 110.303(2) degrees, and gamma = 106.111(2) degrees for 1 and with a = 8.863(7) A, b = 10.241(9) A, c = 11.425(10) A, alpha = 98.985(14) degrees, beta = 110.449(13) degrees, and gamma = 103.664(14) degrees for 2. [Cu2(Pz(3m)2CPh2)2(H2O)2(mu-C2O4)] x NO3 x H2O crystallizes in the monoclinic system, space group C2/c, Z = 4, with a = 23.4588(14) A, b = 8.8568(5) A, c = 21.7818(13) A, alpha = gamma = 90 degrees, and beta = 100.8890(10) degrees. Variable-temperature magnetic susceptibility studies indicate that all four compounds are strongly antiferromagnetically coupled (2J/k = -364, -344 cm(-1) (2), -424 cm(-1) (3), and -378 cm(-1) (4)). Magnetic and EPR results are discussed with respect to structural parameters to explore possible magneto-structural correlations.     

Properties of liquid-crystalline copper(II) complexes and their binary mixtures

Abstract

Eight new copper compounds with mesogenic properties from the series of the bis{1-[4-trans-(4-alkylcyclohexy1)phenyl]-alkylpropane-1,3-dionato} copper(II) complexes have been prepared. The thermal behaviour of these compounds was investigated by means of polarizing microscopy and differential scanning calorimetry (D.S.C.) measurements. The mesophase, which could be found in most of them, is of the monotropic nematic type. This has been confirmed by miscibility experiments. The physical data of a binary mixture with an enantiotropic mesophase are also presented. In addition the crystal structures of two of the compounds are reported.     

The nonisothermal decomposition kinetics of copper(II) complexes with phthalanilic acids and amino acids

Fifteen new kinds of mixed ligand complexes Cu(x‐P)A [P = 2‐(COO)C₆H₄CONH‐C₆H₄; x = H, 2‐Cl, 2‐CH₃, 2‐OCH₃, 4‐OCH₂CH₃; A = dehydronium Met, Leu, Phen] were synthesized. The thermal decomposition behavior of each complex is studied by TG. Coats‐‐Redfern, MacCallum‐‐Tammer, and Zsako methods are adopted to estimate the values of the apparent activation energy E_a, the activation entropy δS^≠, the reaction order n, and the frequency factor A. The results showed that the reaction order is 2/3 for each of the complex. Studies on the mechanism of the thermal decomposition reactions suggested that these reactions all fit the kinetic equation 1 ? (1 ? α)^1/3 = © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 623–628, 2003     

Cobalt(II), copper(II), zinc(II)—Amino and thiosalicylic acids ternary complexes

A series of Co(II), Cu(II), Zn(II)-thiosalicylic-amino acids of the molecular formula (M-TSA-a.a.) · 2 H₂O has been synthesized and characterized by chemical analyses, molar conductance, electronic and i.r. spectral measurements.     

Large pKa shifts of alpha-carbon acids induced by copper(II) complexes

A series of synthetic receptors (4-6) incorporating metal ions, specifically copper(II), were examined for their ability to enhance the acidity of active methylene compounds. The copper(II) complexes were observed to reduce the pKa of 1,3-diketone carbon acids in acetonitrile by as much as 12 pKa units. The relatively large pKa reduction achieved by the complex is attributed to the electrostatic interaction between the anionic pi system of the enolate and the copper(II) ions. The cage structure and hydrogen bonding sites in receptors 4 and 5 lead to a very modest further enhancement of the acidity relative to that with 6. This study provides insight into the way in which metalloenzymes stabilize an enolate intermediate.     

Structure of copper(II) dithiocarbamate mixed-ligand complexes and their photoreactivities in alcohols

The composition of the co-ordination sphere of Cu(II) dithiocarbamate mixed-ligand complexes Cu(Et2)dtc)X (X = Cl-, Br-) and Cu(Et2)dtc)(+)...Y- (Y- = ClO4-, NO3-) is studied from the combined analysis of spectrophotometric and EPR data. The results obtained about CT-photolysis of the complexes in EtOH and i-PrOH are compared with our previous data of photolysis in chloromethane/ROH solutions. Reaction mechanism and the role of alcohol are discussed on the ground of electronic and EPR spectra and quantum yield results.     

Studies on the mixed-ligand complexes of copper(II) with gallic acid and pyridine carboxylic acids and their benzologues

Summary The ternary complex formation of copper(II) with gallic acid (gal) and 2-hydroxy nicotinic acid (hyna), 2-mercapto nicotinic acid (mena), salicylic acid (sa) or thiosalicylic acid (tsa) as a second ligand in a 1:1:1 molar ratio has been investigated in 40% (v/v) ethanol using spectrophotometric andpH titration methods. The solution equilibria of the ternary systems have been determined and the stability constants of the mixed complexes has been evaluated. Considering all parameters, the Cu-gal-sa ternary system was proved as a suitable, rapid, and sensitive spectrophotometric indicator for determining traces of copper.The ternary system containingsa obeysBeer's law up to 3.4 µg·ml^–1 copper. The optimum range for the determination of copper (Ringbom) atpH 6.0 ranges from 0.63 to 1.74 µg·ml^–1 of copper. The molar absorptivity of the ternary complex is 1.3×10⁴l·mol^–1·cm^–1.

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Untersuchungen anmixed-ligand — Komplexen von Kupfer(II) mit 3,4,5-Trihydroxybenzoesäure und Pyridincarbonsäuren und ihren C-Homologen

Zusammenfassung Die Bildung ternärer Komplexe von Kupfer(II) mit 3,4,5-Trihydroxybenzoesäure (gal) und 2-Hydroxynicotinsäure (hyna), 2-Mercaptonicotinsäure (mena), Salicylsäure (sa) oder Thiosalicylsäure (tsa) in einem molaren Verhältnis von 1:1:1 wurde mittels spektrophotometrischer und potentiometrischer Methoden in 40% (v/v) Ethanol untersucht. Die Lösungsgleichgewichte der termären Systeme und die Stabilitätskonstanten der gemischten Komplexe wurden bestimmt. Unter Berücksichtigung aller Parameter erwies sich das termäre System Cu-gal-sa als geeigneter schneller und empfindlicher Indikator zur Spurenanalyse von Kupfer.Dassa enthaltende ternäre System gehorcht demBeerschen Gesetz bis zu einer Kupferkonzentration von 3.4 µg·ml^–1. Der optimale Bereich zur Bestimmung von Kupfer (Ringbom) beipH 6.0 erstreckt sich von 0.63 bis 1.74 µg Cu pro ml. Die molare Extinktion des ternären Komplexes beträgt 1.3×10⁴l·mol·cm^–1.