Complexes of Co(II), Ni(II), Cu(II) and Zn(II) with 3′AMP and 2′AMP

Derivatives of Co(II), Ni(II), Cu(II) and Zn(II) with 3′AMP and 2′AMP were synthesized and characterized by IR UV-Vis and fluorescence spectroscopy. There seems to be bonding of the metal ion to the base in all cases. The activation test, using the complexes as allosteric labels, was carried out with rabbit muscle glycogen phosphorylase b, but the enzyme was not activated, confirming that the phosphate group must necessarily be bonded to position 5′ of the ribose in order to activate this enzyme.     

New synthesis of seven-coordinate complexes of molybdenum(II) and tungsten(II) containing bidentate phosphorus ligands, [MI2(CO)3{Ph2P(CH2)nPPh2}] (n = 1–6)

A new high yielding synthesis of the seven-coordinate complexes [MI₂(CO)₃{Ph₂P(CH₂)_nPPh₂}] (M = Mo and W; n = 1–6) is described. The procedure involves reacting the complexes [MI₂(CO)₃(NCMe)₂] in CH₂Cl₂ with an equimolar amount of the bidentate phosphorus ligand. The low temperature (−70 °C) ¹³C NMR spectra of the complexes [Wl₂(CO)₃{Ph₂P(CH₂)_nPPh₂}] (n = 3 and 5) indicates that the geometry is capped octahedral with a carbonyl ligand in the unique capping position.     

Emission polarization study of the interaction of stellacyanin with tris(2, 2′-bipyridine)osmium(II)

The association of Os(bpy)₃²⁺ and stellacyanin was investigated by measuring the emission polarization of the excited state of the complex [*Os-(bpy)₃²⁺]. At high protein concentration (≥1 mM) Os(bpy)₃²⁺ appears to bind weakly to reduced stellacyanin and to oxidized stellacyanin to a lesser extent. These results are consistent with those obtained in a previous kinetic study on the redox quenching of *Ru(bpy)₃²⁺ by stellacyanin [1]. On excitation at 480 nm, the limiting polarization (P_o) of the *Os(bpy)₃²⁺ emission at 715 nm is 0.100. From P_o we concluded that (1) protein-bound Os(bpy)₃²⁺ has considerable rotational freedom independent of the protein-probe complex, and (2) the emission dipole of *Os(bpy)₃²⁺ is at ∼45° to the C₃ molecular axis.     

Crystal structures of three thiourea (tu) complexes of Pt(II): trans-[(tu)2Pt(NH3)2]Cl2, trans-[(tu)2Pt(CH3NH2)2]Cl2·3H2O and [Pt(tu)4]Cl2

The structures of three Pt(II) thiourea complexes, trans-[(tu)₂Pt(NH₃)₂]Cl₂ (1), trans-[(tu)₂Pt(CH₃NH₂)₂]Cl₂·3H₂O (2) and [Pt(tu)₄]Cl₂ (3), have been determined by X-ray diffraction and refined to R = 0.049 for 1026 reflections (1), R = 0.057 for 2547 reflections (2) and R = 0.046 for 2792 reflections (3). All the compounds crystallize in the space group P2₁/c and have cell dimensions: a = 5.437(1), b = 6.450(1), c = 17.980(3) Å, β = 96.05(2)°, Z = 2 (compound 1); a = 9.225(1), b = 15.404(2), c = 12.601(2) Å, β = 105.39(2)°, Z = 4 (compound 2); and a = 9.051(6), b = 10.203(6), c = 18.263(8) Å, β = 91.12(8)°, Z = 4 (compound 3). The unit cell of 1 and 3 contains only a single type of cation, while that of 2 is formed from two independent cations. In 1 and 2 the coordination spheres of the Pt atoms are rather similar, with angles close to 90° and coplanarity of the metal and respective donor atoms. Instead, in 3 the four sulfur atoms, which surround the Pt, display a slight distortion (0.06 Å from the mean plane) towards tetrahedral.     

Synthesis, Characterization and Antitumor Studies of Mn(II), Ni(II), Cu(II) and Zn(II) Complexes of N-Nicotinoyl-N′-o-Hydroxythiobenzhydrazide

A new ligand N-Nicotinoyl-N-o-hydroxythiobenzhydrazide (H₂Notbh) forms complexes [Mn(Notbh)(H₂O)], [M(Notbh)] [M=Ni(II) Cu(II) and Zn(II)] which were characterized by various physico-chemical techniques. All the metal complexes were observed to inhibit the growth of tumor in vitro, whereas, ligand did not. In vivo administration of these complexes resulted in prolongation of survival of tumor bearing mice. Tumor bearing mice administered with metal complexes showed reversal of tumor growth associated induction of apoptosis in lymphocytes. The paper discusses the possible mechanisms and therapeutic implication of the H₂Notbh and its metal complexes in tumor regression and tumor growth associated immunosuppression.     

Synthesis and characterization of β-diketiminate germanium(II) and tin(II) bromides

The equimolar reaction of a β-diketiminate lithium salt LLi(OEt₂) [L = HC(CMeNAr)₂; Ar = 2,6-iPr₂C₆H₃] with either GeBr₂ or SnBr₂ in diethyl ether affords the synthetically useful monomeric β-diketiminate-element halides LGeBr (1) and LSnBr (2), respectively. Both are soluble in hydrocarbon solvents, stable in inert atmosphere, and have been characterized by elemental analysis, NMR spectroscopy, and single-crystal X-ray diffraction analysis.     

On the mechanism of action of thiamin enzymes, Crystal structure of 2-(α-hydroxyethyl)thiamin pyrophosphate (HETPP). Complexes of HETPP with zinc(II) and cadmium(II)

The crystal structure of the 2-(α-hydroxethyl) thiamin pyrophosphate (LH₂) was solved by X-ray diffraction. Crystallographic data: space group F2dd, a=7.922(4) Å, b=33.11(2) Å, c=36.232(10) Å, V=9503(9) ų, z=16. Metal complexes of the general formula K₂{[M(LH)Cl₂]₂} (M=Zn²⁺, Cd²⁺) were isolated from methanolic solutions and characterized by elemental analysis, IR, Raman, and ¹³C CP MAS NMR spectra. They were also characterized by ¹³C NMR, ³¹P NMR, ¹¹³Cd NMR, ES-MS, and ¹H NMR ROESY spectra in D₂O solutions. The data provide evidence for the bonding of the metals to the N(1′) atom of the pyrimidine ring and to the pyrophosphate group. The free ligand and the metal-coordinated ligand adopt the S conformation. Since thiamin cofactor, substrate, and metal ions are present in our system, the extracted results directly refer to thiamin catalysis and possible functional implications are correlated and discussed.     

Zinc(II) and cadmium(II) metal complexes of thiamine pyrophosphate and 2-(α-hydroxyethyl)thiamine pyrophosphate: models for activation of pyruvate decarboxylase

Metal complexes of thiamine pyrophosphate (TPP) of the general formula [M₂(TPPH)₂Cl₂].4H₂O (M =Zn²⁺, Cd²⁺) were isolated from methanolic solutions and characterized by elemental analysis, FT-IR, and multinuclear NMR spectroscopies. The data provide evidence for the bonding of the metals to the N(1') atom of the pyrimidine ring and to the pyrophosphate group. The stability constant measurements of TPP and 2-(α-hydroxyethyl)thiamine pyrophosphate (HETPP) metal complexes in aqueous solution imply the formation of dimeric complex species similar to the isolated solid products. They indicate also that HETPP forms more stable metal complexes than does TPP. To evaluate the coenzyme action of TPP and HETPP metal complexes, enzymic studies have been done using pyruvate decarboxylase apoenzyme. TPP metal complexes do not bind to the apoenzyme, unlike the Zn(II)-HETPP complex which can act as coenzyme. Considering these results, possible functional implications for thiamine involvement in catalysis are discussed. Received 13 September 1999 / Accepted 4 January 2000     

Cis-diammineplatinum(II) forms a macrochelate with 2′-deoxycytidine 5′-monophosphate (dCMP2–)! Reactivity and acid-base properties of cis-Pt(NH3)2(dCMP)

 The synthesis of cis-Pt(NH₃)₂(dCMP) is reported and by various physico-chemical methods it is demonstrated that it is a macrochelate in which Pt(II) is bound simultaneously to the N3 site of cytosine in dCMP^2– and to a phosphate-oxygen atom. According to the NOESY spectra (cross-peaks between cytosine H6 and H2′ and H3′) the cytosine ring adopts an anti orientation. Highly unusual is the significant (1 ppm) downfield shift of the sugar proton H5″ in the ¹H-NMR spectrum and the sensitivity of the cytosine H6 resonance on the protonation state of the phosphate group. Based on these three features a geometry for the macrochelate is proposed. The compound is a major product of the reaction of cis-[Pt(NH₃)₂(H₂O)₂]²⁺ with dCMP^2– at neutral pH, but it even forms at pH 5. By applying pD-dependent NMR spectroscopy (¹H, ³¹P) and potentiometric pH titration, it is demonstrated that the Pt-coordinated phosphate group can be protonated (pK _a/1=3.21±0.10 and 3.31±0.05, respectively), and ¹H- and ³¹P-NMR spectra also indicate deprotonation (pK _a/2=13.35±0.25) of the exocyclic amino group of the cytosine moiety. The metal ion binding affinity of cis-Pt(NH₃)₂(dCMP) is very small, as shown for Cu²⁺ (log K<0.6). The cis-Pt(NH₃)₂(dCMP) complex reacts with nucleosides and nucleotides (L′) by losing its chelate structure and forming mixed ligand complexes, cis-Pt(NH₃)₂(dCMP)(L′); this means that the phosphate group is released from the coordination sphere of Pt(II), indicating that the Pt(II)-O(phosphate) bond is not very strong. Received: 23 October 1997 / Accepted: 17 February 1998     

Speciation of binary complexes of Co(II), Ni(II) and Cu(II) with L-aspartic acid in propylene glycol–water mixtures

Abstract

Speciation of binary complexes of Co(II), Ni(II) and Cu(II) with L-aspartic acid in (0-60% v/v) propylene glycol-water mixtures was studied pH metrically at 303.0±0.1 K and at an ionic strength of 0.16 mol L^-1. The binary species refined were ML, ML₂, ML₂H₂, ML₂H₃ and ML₂H₄. The stabilities of the complexes followed the Irving-Williams order i.e.Co(II) <Ni(II) < Cu(II). The linear variation of stability constants as a function of dielectric constant of the medium indicated the dominance of electrostatic forces over non-electrostatic forces. Some species were stabilised due to electrostatic interactions and some were destabilised due to the decreased dielectric constant. The order of ingredients influencing the magnitudes of stability constants due to incorporation of errors in their concentrations was alkali > acid > ligand > metal. Equilibria for the formation of binary complexes were proposed based on the forms of the ligand and their existence at different pH values.     

Structural diversity of neutral bis-(β-iminoaldehyde) complexes of nickel(II)

Series of Ni^II and Cu^II complexes with dianionic [N₂O₂] ligands were synthesized and characterised applying spectroscopic and X-ray diffraction techniques. The ligands were obtained by 1:2 condensation of ethylene- and propylenediamine with malonic aldehyde derivatives (R² = H, R¹ = H or OCH₃). Although the molecular formulae of the complexes are quite similar, the X-ray investigations have proved a significant structural diversity in the solid state. Among others, we found some simple nearly planar molecules stacked in the crystal lattice with electron density of six-membered rings delocalised over the chelate rings as well as some very complex polymeric or nickel acetate bridged trinuclear complexes. The coordination of the nickel ion by surrounding oxygen and nitrogen atoms is square-planar in the simplest case and octahedral in the most complex one. Small topological differences in similar molecules generate completely different crystal structures.From magnetic studies, a small, negative value of J obtained confirms the occurrence of weak antiferromagnetic interactions between the Ni^II ions in polymeric chain of the propylenediamine dialdehyde substituted derivative.     

Free metal ion depletion by “good's” buffers: II. N-(2-acetamido)-2-aminoethanesulfonic acid (ACESH): Complexes with Calcium(II), Magnesium(II), Manganese(II), Cobalt(II), Zinc(II), Nickel(II), and Cooper(II)

Potentiometric, visible, and infrared studies of the complexation of N-(2-acetamido)-2-aminoethanesulfonic acid (ACESH) by Ca(II), Mg(II), Mn(II), Co(II), Zn(II), Ni(II), and Cu(II) are reported. Ca(II), Mg(II), and Mn(II) were found not to complex with ACES^?, while Co(II), Zn(II), Ni(II), and Cu(II) were found to form 2:1, ACES^? to M²⁺, complexes, and [Cu(ACES)₂] was found to undergo stepwise deprotonation of the amide groups to form [Cu(H_?1ACES)₂^2?]. Formation (affinity) constants for the various metal complexes are reported, and the probable structures of the various metal chelates in solution are discussed.     

Binuclear metal complexes. 59. Synthesis and magnetism of dicopper(II) and copper(II)-nickel(II) complexes with N,N′-ethylenedisalicylamidatocuprate(II)

The complexes [Cu(samen)Cu(L)] and [Cu(samen)Ni(L)₂] (Lbpy, phen) have been synthesized by the reaction of sodium N,N′-ethylenedisalicylamidatocuprate(II) pentahydrate (Na₂- [Cu(samen)]·5H₂O), a divalent metal ion, and 2,2′- dipyridyl or 1,10-phenanthroline. Cryomagnetic data for the CuCu complexes did not fit the Bleaney- Bowers equation; but the data did fit a modified Bleaney-Bowers equation

with a large negative J and a significant negative θ, suggesting that a considerable magnetic interaction operates between essentially planar [Cu(samen)Cu(L)] molecules. The magnetisms of the CuNi complexes were well interpreted in terms of the susceptibility equation based on the Heisenberg model. An antiferromagnetic spin-exchange interaction (J= −13∼−14 cm⁻¹) was suggested between the metal ions.     

pH-dependence of the specific binding of Cu(II) and Zn(II) ions to the amyloid-β peptide

Metal ions like Cu(II) and Zn(II) are accumulated in Alzheimer's disease amyloid plaques. The amyloid-β (Aβ) peptide involved in the disease interacts with these metal ions at neutral pH via ligands provided by the N-terminal histidines and the N-terminus. The present study uses high-resolution NMR spectroscopy to monitor the residue-specific interactions of Cu(II) and Zn(II) with (15)N- and (13)C,(15)N-labeled Aβ(1-40) peptides at varying pH levels. At pH 7.4 both ions bind to the specific ligands, competing with one another. At pH 5.5 Cu(II) retains its specific histidine ligands, while Zn(II) seems to lack residue-specific interactions. The low pH mimics acidosis which is linked to inflammatory processes in vivo. The results suggest that the cell toxic effects of redox active Cu(II) binding to Aβ may be reversed by the protective activity of non-redox active Zn(II) binding to the same major binding site under non-acidic conditions. Under acidic conditions, the protective effect of Zn(II) may be decreased or changed, since Zn(II) is less able to compete with Cu(II) for the specific binding site on the Aβ peptide under these conditions.     

X-ray absorption spectroscopic analysis of Fe(II) and Cu(II) forms of a herbicide-degrading α-ketoglutarate dioxygenase

 The first step in the degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) by Ralstonia eutropha JMP134 is catalyzed by the α-ketoglutarate (α-KG)-dependent dioxygenase TfdA. Previously, EPR and ESEEM studies on inactive Cu(II)-substituted TfdA suggested a mixture of nitrogen/oxygen coordination with two imidazole-like ligands. Differences between the spectra for Cu TfdA and α-KG- and 2,4-D-treated samples were interpreted as a rearrangement of the g–tensor principal axis system. Herein, we report the use of X-ray absorption spectroscopy (XAS) to further characterize the metal coordination environment of Cu TfdA as well as that in the active, wild-type Fe(II) enzyme. The EXAFS data are interpreted in terms of four N/O ligands (two imidazole-like) in the Cu TfdA sample and six N/O ligands (one or two imidazole-like) in the Fe TfdA sample. Addition of α-KG results in no significant structural change in coordination for Cu or Fe TfdA. However, addition of 2,4-D results in a decrease in the number of imidazole ligands in both Cu and Fe TfdA. Since this change is seen both in the Fe and Cu EXAFS, loss of one histidine ligand upon 2,4-D addition best describes the phenomenon. These XAS data clearly demonstrate that changes occur in the atomic environment of the metallocenter upon substrate binding. Received: 3 July 1998 / Accepted: 13 October 1998     

The mechanism of antimalarial action of the ruthenium(II)–chloroquine complex [RuCl2(CQ)]2

The mechanism of antimalarial action of the ruthenium-chloroquine complex [RuCl(2)(CQ)](2) (1), previously shown by us to be active in vitro against CQ-resistant strains of Plasmodium falciparum and in vivo against P. berghei, has been investigated. The complex is rapidly hydrolyzed in aqueous solution to [RuCl(OH(2))(3)(CQ)](2)[Cl](2), which is probably the active species. This compound binds to hematin in solution and inhibits aggregation to beta-hematin at pH approximately 5 to a slightly lower extent than chloroquine diphosphate; more importantly, the heme aggregation inhibition activity of complex 1 is significantly higher than that of CQ when measured at the interface of n-octanol-aqueous acetate buffer mixtures under acidic conditions modeling the food vacuole of the parasite. Partition coefficient measurements confirmed that complex 1 is considerably more lipophilic than CQ in n-octanol-water mixtures at pH approximately 5. This suggests that the principal target of complex 1 is the heme aggregation process, which has recently been reported to be fast and spontaneous at or near water-lipid interfaces. The enhanced antimalarial activity of complex 1 is thus probably due to a higher effective concentration of the drug at or near the interface compared with that of CQ, which accumulates strongly in the aqueous regions of the vacuole under those conditions. Furthermore, the activity of complex 1 against CQ-resistant strains of P. falciparum is probably related to its greater lipophilicity, in line with previous reports indicating a lowered ability of the mutated transmembrane transporter PfCRT to promote the efflux of highly lipophilic drugs. The metal complex also interacts with DNA by intercalation, to a comparable extent and in a similar manner to uncomplexed CQ and therefore DNA binding does not appear to be an important part of the mechanism of antimalarial action in this case.     

Preparation and characterization of oxovanadium(IV), acetatomanganese(III), chloroiron(III), nickel(II), copper(II), zinc(II) and palladium(II) complexes of 3,3′-(1,2-phenylenediimino)diacrolein

The oxovanadium(IV), acetatomanganese(III), chloroiron(III), nickel(II), copper(II), zinc(II) and palladium(II) of 3,3′-(1,2-phenylenediimino)diacrolein were prepared and investigated by means of mass, electronic, vibrational, NMR and ESR spectroscopy as well as magnetic susceptibility measurements. The acetatomanganese(III) and chloroiron(III) complexes were confirmed to be of high spin type. The absorption bands appearing in the energy range greater than 23 000 cm⁻¹ were attributed to π→π^* transitions within a ligand molecule and charge- transfer transitions from metal to ligand. The metal complexes assume the square-planar configuration type since the ligand-field bands were detected in the 12 700–18 500 cm⁻¹ region. Strong bands appearing at 1601 and 1627 cm⁻¹ were assigned to the CC and CO stretching vibrational modes, respectively, and were shifted to lower frequency upon metal-coordination. A VO stretching band was observed at 982 cm⁻¹ for the oxovanadium(IV) complex and a CO stretching band was observed at 1547 cm⁻¹ for the acetatomanganese(III) complex. Upon complex formation the amine proton signal is found to vanish and the aldehydic methine proton signal in the lowest field is shifted upfield for the nickel(II), zinc(II) and palladium(II) complexes. ¹³C NMR spectra support the coordination structure of the complexes which is revealed by ¹H NMR spectra. As judged by the spin Hamiltonian parameters, the oxovanadium(IV) complex is of a square- planar type with an unpaired electron in the d_xy orbital and the copper(II) complex assumes a distorted square-planar coordination due to the presence of five- and six-membered chelate rings with an unpaired electron in the d_x2−y2 orbital.