Solution properties of Cu(II)-L-α-alaninehydroxamic acid

In the aqueous solution of copper(II) ions, bidentate L-α-alaninehydroxamic acid (CH₃CH(NH₂)-CONHOHHL) binds cupric ion forming of monodimeric and bis(L-α-alaninehydroxamato)copper(II) complexes. These complexes were studied by potentiometric, ESR and spectrophotometric methods.The ESR studies provide important evidence for the formation of different Cu(II) complexes with L-α-alaninehydroxamic acid, depending on pH. The ESR spectra can be used to follow the appearance of the individual complexes, to estimate the coordination sphere around Cu(II) and to observe the equilibria between different complexes.The solution electronic spectra are reported. The experimental curve was resolved into precise- positioned absorption bands by Gaussian analysis for the bis(L-α-alaninehydroxamato)copper(II) species. These data were used in a weak tetragonal ligand field model to calculate ligand field parameters.The distribution and the relevant stability constants of species present in aqueous solutions were obtained by analytical potentiometry.     

The redox properties of (1,6-bis(benzimidazol-2-yl)-2,5-dithiahexane) chloro-copper(II) chloride as studied by cyclic voltammetry

Cyclic voltammetry in acetonitrile has been used to study the redox properties of the compound [Cu-(BBDH)Cl] Cl under various conditions. The nature of the species in solution was studied with the aid of ligand-field spectra and ESR spectra. It appears that in CH₃CN solution two Cu(II) species are predominating, viz. [Cu(BBDH)(CH₃CN)_x]²⁺ and Cu(BBDH)-Cl⁺. Minor species are dimeric in nature, such as [(BBDH)CuCl₂Cu(BBDH)]²⁺, as easily seen from ESR. The relative amount of the two major species was varied using added LiCl, allowing us to determine the nature of both species. The redox potential of the species [Cu(BBDH)Cl]⁺ appeared to be 0.62 V (against a normal hydrogen electrode), which is very high for a Cu(II) compound and in the same area as found for the blue copper proteins. Re-oxidation of Cu(BBDH)⁺ in the presence of LiCl shows that C$\text{l}$ slowly recoordinates after reoxidation.     

Binding of copper(II) to thyrotropin-releasing hormone (TRH) and its analogs

Spectroscopy (UV-Vis, ¹H NMR, ESR) and electrochemistry revealed details of the structure of the Cu(II)-TRH (pyroglutamyl-histidyl-prolyl amide) complex. The ¹H NMR spectrum of TRH has been assigned. NMR spectra of TRH in the presence of Cu(II) showed that Cu(II) initially binds TRH through the imidazole. TRH analogs, pGlu-His-Pro-OH, pGlu-(1-Me)His-Pro-amide, pGlu-His-(3,4-dehydro)Pro-amide, pGlu-His-OH, pGlu-Glu-Pro-amide, and pGlu-Phe-Pro-amide provided comparison data. The stoichiometry of the major Cu(II)-TRH complex at pH 7.45 and greater is 1:1. The conditional formation constant (in pH 9.84 borate with 12.0 mM tartrate) for the formation of the complex is above 10⁵ M⁻¹. The coordination starts from the 1-N of the histidyl imidazole, and then proceeds along the backbone involving the deprotonated pGlu-His amide and the lactam nitrogen of the pGlu residue. The fourth equatorial donor is an oxygen donor from water. Hydroxide begins to replace the water before the pH reaches 11. Minority species with stoichiometry of Cu-(TRH)_x (x = 2-4) probably exist at pH lower than 8.0. In non-buffered aqueous solutions, TRH acts as a monodentate ligand and forms a Cu(II)-(TRH)₄ complex through imidazole nitrogens. All the His-containing analogs behave like TRH in terms of the above properties.     

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.     

Synthesis, characterisation and structural studies of [Cu(dach)(μ-NCS)(NCS)]n and [Cu(dach)2(N3)]ClO4 (dach=1,4-diazacycloheptane)

A new singly bridging complex [Cu(dach)(μ-NCS)(NCS)]_n (dach=1,4-diazacycloheptane) has been synthesised and its crystal structure determined. There are many examples of double NCS bridged polymeric chains, but fewer singly bridged ones. IR, ESR and temperature variable magnetic studies are described but no magnetic interaction was found between the copper centres. [Cu(dach)₂(N₃)]ClO₄ has also been characterised by IR, ESR spectra and magnetic studies. The crystal structure determination shows that it is a penta-coordinated monomeric species with an axially coordinated azide linked to the perchlorate counterion by hydrogen bonding.     

Copper(II) complexation by D-glucosamine. Spectroscopic and potentiometric studies

The Cu(II) complex formation equilibria of D- glucosamine were studied in aqueous solution by potentiometric and spectroscopic (ESR, CD, absorption spectra) techniques. All data agree that two major species are formed in the pH region 6–9 involving two D-glucosamine ligand molecules bound to the cupric ion via NH₂(CuL₂) or NH₂ and O^? (CuH_?2L₂). In the latter case deprotonated hydroxyls were found to be very effective coordination sites for Cu(II) giving rise to chelate complexes. On the contrary, no complex formation was observed for the Cu(II) N-acetyl-D-glucosamine system.     

Heme complexes of rabbit hemopexin,human hemopexin and human serum albumin: Electron spin resonance and Mőssbauer spectroscopic studies

The electron spin resonance (ESR) spectra of human and rabbit ferriheme-hemopexin complexes at 30^oK show an ESR absorption characterized by g_x = 1.60, g_y = 2.25 and g_z = 2.86, characteristic of low-spin ferriheme-proteins. The low-spin nature of the heme-iron in heme-hemopexin is corroborated by the observation of nuclear hyperfine splitting in M?ssbauer spectra at 4.2^oK. The similarity of the ESR spectra of ferriheme-hemopexin with those of low-spin cytochromes which coordinate heme via two histidine residues points to a similar coordination mechanism in hemopexin. In contrast, the ESR spectra of the 1:1 and 2:1 complexes of heme with human serum albumin display signals at g = 6.0 and g = 2.0, characteristic of high-spin ferrihemeproteins.     

Characterization of the reduction steps of Fe(III) porphyrins

Polarographic studies have shown that Fe(III) porphyrins undergo successively three one-electron reduction steps in dimethylformamide. The first involves the Fe(III)/Fe(II) redox couple. The second step proceeds to a second reduction of the metal ion and is attributed to the Fe(II)/Fe(I)_couple. This new reduction state of iron porphyrins has been characterized by ESR spectra and by absorption spectra in various solvents. This compound is not axially liganded by strong nucleophilic bases but is sensitive to solvation, the lone electron being localised in the d_z2 orbital. The third reduction step is assumed to involve a reduction of the porphyrin π-electron system.All these results have been confirmed by chemical reductions in tetrahydrofuran.     

Complexes of d(+)-biotin with Pd(II) and Pt(II)

The reactions of d(+)-biotin with K₂MX₄, where M = Pd(II) or Pt(II) and X = Cl or Br have been studied in acidic, neutral or alkaline aqueous solutions. Complexes of the type trans-M(Bio)₂X₂ have been isolated for both metals and characterized with elemental analyses, conductivity measurments, ir spectra, ¹Hnmr and ¹³Cnmr spectra. The complex of the type [Pd(Bio)Cl₂]₂ has also been isolated from DMF solutions. The results indicate that d(+)-biotin coordinates exclusively through its sulfur atom with these metals in all the complexes in the present study, in the solid state or in solution.     

Metallobleomycins: electron spin resonance study on nitrosyl complex of iron(II)-Bleomycin

The ESR spectrum of the bleomycin-Fe(II)NO complex shows rhombic symmetry with a triplet hyperfine interaction in the g_z signal, and its ESR parameters have been compared with those of the ferrous-NO complexes of hemoproteins. The substitution of ₁₄NO by ₁₅NO gives the transition from a triplet to a doublet in the g_z absorption with a concomitant change in the nitrogen hyperfine constant. The addition of DNA to the ferrous-NO complex of bleomycin induces the greater separation of the g_x and g_y absorptions in comparison with the original ESR spectrum. The present three-line g_z signal for the bleomycin-Fe(II)-NO complex is indicative of weakened fifth axial nitrogen ligand-to-iron bonding with concomitantly stronger NO-to-iron bonding. On the other hand, the ESR feature of the bleomycin-Fe(III) complex is typical of the rhombic low-spin type, and no stable ferric-NO complex of bleomycin is formed.     

Stoichiometric aerobic aminohydroxylation of ethylene mediated by dpms-platinum complexes (dmps = di(2-pyridyl)methanesulfonate)

Chloro di(2-pyridyl)methanesulfonate ethylene platinum(II) complex was converted to corresponding N-alkylplatina(II)azetidines by reacting the former with primary amines, MeNH₂ and tert-BuNH₂, to produce 2-ammonioethyl chloro platinum(II) species and their subsequent cyclization in the presence of NaOH in methanol. The N-alkylplatina(II)azetidines are oxidized under air or the atmosphere of pure O₂ to the corresponding N-alkylplatina(IV)azetidines in water or in methanol solution in the presence of one equivalent of a strong acid under ambient pressure at 22 °C. The resulting N-alkylplatina(IV)azetidines undergo C-O reductive elimination in acidic aqueous solutions to produce 2-(N-alkylamino)ethanols.     

Two series of copper(II) complexes derived from various 2-urethanylpyridine N-oxides (2-ethoxycarbonylaminopyridine N-oxides)

A series of new aromatic N-oxide ligands have been prepared by converting the 2-amino group of 2-aminopyridine N-oxide, 2-aminopicoline N-oxides and 2-amino-4,6-lutidine N-oxide into a urethane. Two series of copper(II) complexes have been prepared and characterized by their infrared, electronic and ESR spectra along with other physicochemical methods. One series has the stoichiometry [Cu(UOH)₄](ClO₄)₂ and involves monodentate coordination via the N-oxide oxygen and the other series is prepared from copper(II) acetate and has the stoichiometry [Cu(UO)₂]. In this latter series coordination occurs via the _N-oxide oxygen and the deprotonated amino function.     

Responsive Mn(II) complexes for potential applications in diagnostic Magnetic Resonance Imaging

The investigation of new Mn(II)-based MRI/Molecular Imaging probes responsive to the enzyme tyrosinase for potential diagnostic applications is herein described. The expression of the enzyme tyrosinase, an oxidoreductase, is up-regulated in melanoma cancer cells. Three novel ligands (L₁, L₂ and L₃) were designed as modified acyclic polyaminocarboxylate chelates by introducing an l-tyrosine residue in place of an aminoacetate unit. The corresponding Mn(II) complexes were fully characterised by ¹H NMR relaxometric techniques in aqueous media. The responsive activity towards the expression of tyrosinase was then assessed by monitoring the ¹H 1/T₁ relaxivity changes during incubation experiments in buffered solutions containing tyrosinase at different concentrations and in B16F10 melanoma cell homogenate. New insight on the mechanism of action of these systems was gained by measuring the magnetic field dependence of the relaxivity and ESR spectra of the incubated solutions. The systems developed showed responsive activity to tyrosinase with a relaxation enhancement spanning from 50% (MnL₁) to 350% (MnL₃) which augurs well for the development of diagnostic probes to detect melanoma cancer.     

Seven coordinate complexes of metal(II) nitrates

ESR spectra at both X and Q band are reported for manganese(II) ions doped into the seven coordinate complexes M(L)₃(NO₃)₂ (M = Co, Ni, Zn or Cd; L = pyridine or substituted pyridine). The zero field splitting parameters D and λ (= E/D) are deduced. All complexes show considerable deviation from cubic symmetry, as can be expected for a seven coordinate structure. The distinctly lower D value of Ni(Mn)(pyridine)₃(NO₃)₂, as compared to the analogous cobalt and zinc complex, suggests a geometry tending towards an octahedral structure. The steric hindrance by the substituent reduces the D value.     

Electron spin resonance and electron nuclear double resonance studies of cation radicals derived from tocopherol model compounds

Electron spin resonance (ESR) and electron nuclear double resonance (ENDOR) measurements were performed for the cation radicals obtained from the model compounds of α-, β-, γ- and δ-tocopherol (vitamin E) by oxidizing the tocopherol precursors in an AlCl₃-CH₂Cl₂ solution. The proton hyperfine coupling constants g-values were precisely determined. The ENDOR spectra of the cation radicals of α-, β-, γ- and δ-tocopherol models in CH₂Cl₂ at ?100°C clearly show 10, 6, 6 and 12 different proton hyperfine couplings, respectively. By varying the temperature, the ESR spectra of the α- and δ-tocopherol model cations exhibit line-width alternation phenomena characteristic of the hindered rotation of the OH group. However, neither the β- nor the γ-tocopherol model cation radical ESR spectra show any sign of an alternative line-width effect. These results are interpreted by assuming that the β- and γ-tocopherol model cations are stabilized in the trans and cis conformations, respectively. On tocopherol model cations are stabilized in the trans and cis conformations, respectively. On the other hand, both the α- and δ-tocopherol model cations exist as cis and trans isomers.     

Synthesis,characterization and antitumor activity of some metal complexes of 3- and 5-substituted salicylaldehyde o-hydroxybenzoylhydrazones

Complexes of Mn(II), Fe(III), Fe(II), Co(II), Ni(II), Cu(II), Zn(II) and Pt(II) with 3- and 5-substituted salicylaldehyde o-hydroxybenzoylhydrazones (XSBH, X = H, 3-NO₂, 3-CH₃O, 5-Cl, 5-Br, 5-CH₃ or 5-NO₂) have been prepared and characterized by elemental analysis, conductance measurements, magnetic susceptibilities (from room temperature down to liquid nitrogen temperature) and spectral studies. These studies indicate the following structures: monomeric, high-spin, distorted octahedral for Mn(XSBH)₂; monomeric, high-spin, five-coordinate for Fe(XSBH)SO₄·H₂O; dimeric, high-spin phenoxide bridged, five-coordinate for Fe(XSBH)Cl; dimeric, high-spin five-coordinate for Co(XSBH)Cl·2H₂O; dimeric low-spin, five-coordinate for Ni(XSBH)Cl·2H₂O; dimeric, four-coordinate for Zn(XSBH); and a square-planar structure for M(XSBH)Cl·H₂O (M = Cu(II) or Pt(II).Intermolecular antiferromagnetic exchange interactions are present in Fe(III) complexes, where the exchange parameter (J) is ca. −8.0 cm⁻¹ for these complexes. The Fe(III) complexes exhibit asymmetric quadrupole split doublets in their ⁵⁷Fe Mössbauer spectra. The asymmetry is found to be temperature dependent with relatively symmetrical doublets seen at low temperature. The polycrystalline ESR spectra of Cu(II) complexes are isotropic and indicate a d_x²−y² ground state in square-planar stereo-chemistry. All these metal complexes have been screened for their antitumor activity against the P 388 lymphocytic leukaemia test system in mice and enhanced antitumor activity relative to the free ligand was found but no significant activity at the dosages used.     

Cadmium(II) complex formation with glutathione

Complex formation between heavy metal ions and glutathione (GSH) is considered as the initial step in many detoxification processes in living organisms. In this study the structure and coordination between the cadmium(II) ion and GSH were investigated in aqueous solutions (pH 7.5 and 11.0) and in the solid state, using a combination of spectroscopic techniques. The similarity of the Cd K-edge and L₃-edge X-ray absorption spectra of the solid compound [Cd(GS)(GSH)]ClO₄·3H₂O, precipitating at pH 3.0, with the previously studied cysteine compound {Cd(HCys)₂·H₂O}₂·H₃O⁺·ClO₄ ^? corresponds to Cd(S–GS)₃O (dominating) and Cd(S–GS)₄ four-coordination within oligomeric complexes with mean bond distances of 2.51 ± 0.02 Å for Cd–S and 2.24 ± 0.04 Å for Cd–O. For cadmium(II) solutions (C _Cd(II) ~ 0.05 M) at pH 7.5 with moderate excess of GSH (C _GSH/C _Cd(II) = 3.0–5.0), a mix of Cd(S–GS)₃O (dominating) and Cd(S–GS)₄ species is consistent with the broad ¹¹³Cd NMR resonances in the range 632–658 ppm. In alkaline solutions (pH 11.0 and C _GSH/C _Cd(II) = 2.0 or 3.0), two distinct peaks at 322 and 674 ppm are obtained. The first peak indicates six-coordinated mononuclear and dinuclear complexes with CdS₂N₂(N/O)₂ and CdSN₃O₂ coordination in fast exchange, whereas the second corresponds to Cd(S–GS)₄ sites. At high ligand excess the tetrathiolate complex, Cd(S–GS)₄, characterized by a sharp δ(¹¹³Cd) NMR signal at 677 ppm, predominates. The average Cd–S distance, obtained from the X-ray absorption spectra, varied within a narrow range, 2.49–2.53 Å, for all solutions (pH 7.5 and 11.0) regardless of the coordination geometry.     

Electrogenerated chemiluminescence from osmium(II) polypyridine carbonyl chloride systems

The spectroscopy, electrochemistry and electrogenerated chemiluminescence (ECL) of four osmium(II) phenanthroline carbonyl chloride complexes are reported. Three of these compounds also contain diphosphine chelating ligands. ECL is generated in acetonitrile solutions with tri-n-propylamine (TPrA) as an oxidative-reductive coreactant. ECL efficiencies (?_ecl = photons emitted per redox event) between 0.011 and 0.13 were obtained in air saturated and deoxygenated solutions with Ru(bpy)₃²⁺ (bpy = 2,2′-bipyridine) as a relative standard (?_ecl = 1). The ECL intensity peaks at a potential corresponding to oxidation of both TPrA and the osmium systems, while ECL spectra (obtained using absorption filters) are similar to photoluminescence spectra, indicating that emission is from the excited states of the osmium complexes.     

Cadmium tri-tert-butoxysilanethiolates: Structural and spectroscopic models of metal sites in proteins

Syntheses and crystal structures of two molecular, heteroleptic cadmium complexes with CdS₂NO₂ and CdS₂N₂ kernels are described. Bis(tri-tert-butoxysilanethiolate)(1-methylimidazole)cadmium(II) and bis(tri-tert-butoxysilanethiolate)bis(1-methylimidazole)cadmium(II) coexist at equilibrium in chloroform solutions with varying concentrations of bis[bis(tri-tert-butoxysilanethiolate)cadmium(II)] and 1-methylimidazole. The equilibrium is characterized by solution ¹¹³Cd NMR spectra. Solid state CP MAS ¹³C, ²⁹Si, ¹¹³Cd NMR data for the complexes are also reported, analyzed and compared with the results obtained for cadmium-substituted proteins. The similarities and differences between the structures of cadmium complexes and their zinc analogues are discussed.     

Acridine spin labels as probes for nucleic acids.

Adridine spin labels, 4-[9-(6-chloro-2-methoxy)-acridylamino]- 2,2,6,6-tetramethyl-1-piperidinyloxy (I) and 4-(9-acridylamino)- 2,2,6,6-tetramethyl-1-piperidinyloxy (II), have been synthesized and their interaction with nucleic acids studied by means of electron spin resonance (ESR). The ESR spectra of labels I and II in the presence of calf thymus DNA were characteristic of highly immobilized nitroxide radicals with maximum hyperfine splittings (2T_ˌˌ) of 58.7 and 55.5 G, respectively. The melting temperature (T_m) of DNA, determined in the presence of labels I and II by the ESR technique, were closely similar to those obtained by spectrophotometric methods. The ESR spectrum of label I bound to calf liver RNA and yeast RNA indicated that the nitroxide group of this label was highly mobile. These results suggest that spin labels I and II are suitable noncovalent probes for nucleic acids.