Study of the antidiabetic capacity of the VO(dmpp)2 complex

In this work we report biochemical ex vivo studies with a vanadium compound containing a pyridinone ligand, the bis(1,2-dimethyl-3-hydroxy-4-pyridinonate)oxovanadium (IV), V^IVO(dmpp)₂, which has shown to have promising antidiabetic activity. The experiments were carried out on primary adipocytes of 6-8 week old Wistar rats. Insulin-stimulated glucose uptake studies were performed using a radioactive assay by measuring the (U)-¹⁴C-glucose taken up by the isolated adipocytes for 30 min. Adipocytes were incubated with and without insulin and in the presence and absence of different concentrations of V^IVO(dmpp)₂ (100-500 μM) for 45 min. We observed that in a nontoxic concentration, as demonstrated by the Alamar Blue test, V^IVO(dmpp)₂ significantly increases glucose uptake, in the absence of insulin, by 5-folds higher than basal, and it has a significant inhibitory effect of 78% on free fatty acid release in isolated adipocytes from normal rats. We also demonstrated that it promotes the phosphorylation of Akt1, a key protein in the insulin signaling cascade. These results were compared with those obtained with another vanadium compound reported in the literature, with a similar structure, the bis(maltolato)oxovanadium (IV) (BMOV), which is now in clinical trials. Our ex vivo results clearly indicate that V^IVO(dmpp)₂ is a good candidate to be a promising drug for the treatment of diabetes and other metabolic disorders.     

The Pharmacology of the Insulinomimetic Effect of Zinc Complexes

In developing new insulinomimetic zinc(II) complexes with different coordination structures and with a blood glucose-lowering effect to treat type 2 diabetic animals, we found a potent bis(maltolato)zinc(ll) complex, Zn(mal)₂. Using the complex as the leading compound, we examined the in vitro and in vivo structure-activity relationships of Zn(mal)₂ and its related complexes in respect to the inhibition of free fatty acids (FFA) release and the enhancement of glucose uptake in isolated rat adipocytes treated with epinephrine (adrenaline), and hypoglycemic activity. Among the compounds tested, a new Zn(II) complex with allixin that was isolated from garlic, bis(allixinato)Zn(II), Zn(alx)₂, was found to exhibit the highest insulin-mimetic and hypoglycemic activities in type 2 KK-A^y diabetic mice. On the basis of the results, Zn(alx)₂, complex was proposed to be a potent candidate for the treatment of type 2 diabetes.     

Synthesis and structure of cadmium and zinc complexes of dehydroacetic acid

The cadmium and zinc complexes of Dehydroacetic Acid (DHA) Zn(DHA)₂(H₂O)₂ and Cd(DHA)₂(H₂O)₂ were synthesized and the derivatives Zn(ADH)₂(DMSO)₂ and Cd(ADH)₂(DMSO)₂ were prepared through substitution of the water ligands by DMSO. To characterize structural differences between the Cd and Zn complexes, a series of analyses were carried out: ¹H, ¹³C, and ¹¹³Cd NMR in solution and ¹³C and ¹¹³Cd NMR in the solid state, infra-red spectra, thermo gravimetric analysis (TGA), differential calorimetric analysis (DSC) and elemental analysis (CHNO). The X-ray crystal structures of the complexes Zn(DHA)₂(DMSO)₂ and Cd(DHA)₂(DMSO)₂ are also reported. The coordination around the metal atoms in the solid state is best described as distorted octahedra. The two chelating DHA ligands define an equatorial plane and the axial positions are occupied by two monodentate DMSO ligands coordinated by oxygen atoms, in the trans,trans,trans configuration. Significant differences were found between the Cd and Zn coordination spheres, with the latter forming relatively looser octahedral complexes.     

Nitroimidazole conjugates of bis(thiosemicarbazonato)Cu(II) - Potential combination agents for the PET imaging of hypoxia

Combination agents comprising two different pharmacophores with the same biological target have the potential to show additive or synergistic activity. Bis(thiosemicarbazonato)copper(II) complexes (e.g. ⁶⁴Cu-ATSM) and nitroimidazoles (e.g. ¹⁸F-MISO) are classes of tracer used for the delineation of tumor hypoxia by positron emission tomography (PET). Three nitroimidazole-bis(thiosemicarbazonato)copper(II) conjugates were produced in order to investigate their potential as combination hypoxia imaging agents. Two were derived from the known bifunctional bis(thiosemicarbazone) H₂ATSM/A and the third from the new precursor diacetyl-2-(4-N-methyl-3-thiosemicarbazone)-3-(4-N-ethylamino-3-thiosemicarbazone) - H₂ATSM/en. Oxygen-dependent uptake studies were performed using the ⁶⁴Cu radiolabelled complexes in EMT6 carcinoma cells. All the complexes displayed appreciable hypoxia selectivity, with the nitroimidazole conjugates displaying greater selectivity than a simple propyl derivative used as a control. Participation of the nitroimidazole group in the trapping mechanism is indicated by the increased hypoxic uptake of the 2- vs. the 4-substituted ⁶⁴Cu-ATSM/A derivatives. The 2-nitroimidazole derivative of ⁶⁴Cu-ATSM/en demonstrated superior hypoxia selectivity to ⁶⁴Cu-ATSM over the range of oxygen concentrations tested. Biodistribution of the radiolabelled 2-nitroimidazole conjugates was carried out in EMT6 tumor-bearing mice. The complexes showed significantly different uptake trends in comparison to each other and previously studied Cu-ATSM derivatives. Uptake of the Cu-ATSM/en conjugate in non-target organs was considerably lower than for derivatives based on Cu-ATSM/A.     

Evaluation of insulin-mimetic activities of vanadyl and zinc(II) complexes from the viewpoint of heterocyclic bidentate ligands

Vanadyl sulfate (VOSO₄) has been clinically tested in diabetic patients since 1995. Oral administrations of VOSO₄ improved the type 2 diabetic state with respect to plasma glucose, HbA_1c, and fructosamine levels. The development of toxicity by increasing the administration of VOSO₄ should be avoided. One method was the utilization of vanadyl complexes with coordination compounds that are low-toxic and low-molecular-weight ligands to enhance the permeation of the metal ion to lipid bilayer membrane. Over a decade we have focused on a variety of heterocyclic compounds as bidentate ligands for metal ions. Vanadyl and zinc(II) complexes of 1-substituted 3-hydroxy-2-methyl-4(1H)-pyridinethiones, 4,5,6-substituted 1-hydroxy-2(1H)-pyrimidinones, 4-(p-substituted)phenyl-3-hydroxythiazole-2(3H)-thiones, 3-hydroxypyrone, 1-alkyl- or 1-phenylalkyl-3-hydroxy-2(1H)-pyridinethiones, optically active 1-substituted 3-hydroxy-4(1H)-pyridinethiones, and 5-dialkylsulfonamido- or 5,7-bis(dialkylsulfonamido)-8-hydroxyquinolines were prepared, and their insulin-mimetic activities were evaluated in terms of IC₅₀ values which stand for a 50% inhibitory concentration of the free fatty acid release from isolated rat adipocytes. In this article, the relationship between the insulin-mimetic activity and the partition coefficient, the chirality, the substituent effect, molecular weight, the pK_a value, and the coordination mode was discussed. In vivo blood glucose-lowering effects of the vanadyl complex with 1-hydroxy-4,6-dimethyl-2(1H)-pyrimidinone in streptozotocin (STZ)-induced diabetic rats and the zinc(II) complexes with 4-(p-chlorophenyl)thiazole- and 4-methylthiazole-2(3H)-thione in KK-A^y mice were also discussed.     

Preparation, characterisation and crystal structure of two zinc(II) benzoate complexes with pyridine-based ligands nicotinamide and methyl-3-pyridylcarbamate

Two benzoate complexes namely tetrakis(μ₂-benzoato-O,O^′)-bis(μ₂-benzoato-O,O)-bis(nicotinamide-N)-tri-zinc(II), [Zn₃(benz)₆(nia)₂] (I) and bis(benzoato-O)-bis(methyl-3-pyridylcarbamate-N)-zinc(II), [Zn(benz)₂(mpcm)₂] (II) (benz=benzoate anion, nia=nicotinamide, mpcm=methyl-3-pyridylcarbamate) were prepared and characterised by elemental analysis, IR spectroscopy, thermal analysis and X-ray structure determination. The structure of the complex I is centrosymmetric, formed by a linear array of three zinc atoms. The central zinc atom shows octahedral coordination and is bridged to each of the terminal zinc atoms by three benzoate anions. Two of them act as bidentate, one as monodentate ligand. By additional coordination of the nia ligand, the terminal Zn atoms adopt tetrahedral surrounding. The structure of complex II contains two crystallographically independent [Zn(benz)₂(mpcm)₂] molecules. In each molecule, the zinc atom is tetrahedrally coordinated by two monodentate benzoate and two methyl-3-pyridylcarbamate ligands. Intermolecular hydrogen bonds of the N-H?O type connect molecules in the structures of complexes I and II to form a two-dimensional network. The three different types of carboxylate binding found in the complexes were distinguished also by values of carboxylate stretching vibrations in FT-IR spectra as well as by thermal decomposition of the complexes in nitrogen.     

A new insulin-mimetic bis(allixinato)zinc(II) complex: structure–activity relationship of zinc(II) complexes

During the investigation of the development of insulin-mimetic zinc(II) complexes with a blood glucose-lowering effect in experimental diabetic animals, we found a potent bis(maltolato)zinc(II) complex, Zn(ma)₂, exhibiting significant insulin-mimetic effects in a type 2 diabetic animal model. By using this Zn(ma)₂ as the leading compound, we examined the in vitro and in vivo structure–activity relationships of Zn(ma)₂ and its related complexes. The in vitro insulin-mimetic activity of these complexes was determined by the inhibition of free fatty acid release and the enhancement of glucose uptake in isolated rat adipocytes treated with epinephrine. A new Zn(II) complex with allixin isolated from garlic, Zn(alx)₂, exhibited the highest insulin-mimetic activity among the complexes analyzed. The insulin-mimetic activity of the Zn(II) complexes examined strongly correlated (correlation coefficient=0.96) with the partition coefficient (logP) of the ligand, indicating that the activity of Zn(ma)₂-related complexes depends on the lipophilicity of the ligand. The blood glucose-lowering effects of Zn(alx)₂ and Zn(ma)₂ were then compared, and both complexes were found to normalize hyperglycemia in KK-A^y mice after a 14-day course of daily intraperitoneal injections. However, Zn(alx)₂ improved glucose tolerance in KK-A^y mice much more than did Zn(ma)₂, indicating that Zn(alx)₂ possesses greater in vivo anti-diabetic activity than Zn(ma)₂. In addition, Zn(alx)₂ improved leptin resistance and suppressed the progress of obesity in type 2 diabetic KK-A^y mice. On the basis of these observations, we conclude that the Zn(alx)₂ complex is a novel potent candidate for the treatment of type 2 diabetes mellitus.Electronic Supplementary Material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00775-004-0590-8     

Model complexes of the active site of galactose oxidase. Effects of the metal ion binding sites

Model compounds of the active site of galactose oxidase have been developed by using new cofactor model ligands, L1H (2-methylthio-4-tert-butyl-6-[{bis(pyridin-2-ylmethyl)amino}methyl]phenol) and L2H (2-methylthio-4-tert-butyl-6-[{bis(6-methylpyridin-2-ylmethyl)amino}methyl]phenol). Treatment of the ligands with copper(II) and zinc(II) perchlorate in the presence of triethylamine followed by anion exchange reaction with NaPF₆ or NaBPh₄ provided the corresponding copper(II) and zinc(II) complexes, the crystal structures of which have been determined by X-ray crystallographic analysis. All the copper(II) and zinc(II) complexes have been isolated as a dimeric form in which the phenolate oxygen of each ligand acts as the bridging ligand to form a rhombic M₂(OAr)₂ core (M=Cu or Zn). The dimeric complexes can be converted into the corresponding monomer complexes by the treatment with exogenous ligand such as acetate ion. The redox potential and the spectroscopic features of the monomer complexes have also been examined. Furthermore, the copper(II)- and zinc(II)-complexes of the phenoxyl radical species of the ligands have been generated in situ by the oxidation of the phenolate complexes with (NH₄)₂[Ce^IV(NO₃)₆] (CAN) in CH₃CN, and their spectroscopic features have been explored. The structures and physicochemical properties of the phenolate and phenoxyl radical complexes of L1 and L2 have been compared to those of the previously reported copper(II) and zinc(II) complexes of L3 (2-methylthio-4-tert-butyl-6-[{bis(2-pyridin-2-ylethyl)amino}methyl]phenol) in order to get insights into the interaction between the metal ions and the organic cofactor moiety.     

Synthesis and characterization of two new triazolate-aliphatic dicarboxylate bridged Zn(II) coordination polymers based on 2D layer motifs with different crystal packing

Two new zinc(II)-triazole-aliphatic dicarboxylate coordination polymers, [Zn(trz)(Hsuc)]_n (1), [Zn₂(trz)₂(tar)]_n (2), have been hydrothermally synthesized by reaction of Zn salt, Htrz with H₂suc and H₂tar, respectively (Htrz = 1,2,4-triazole, H₂suc = succinic acid, H₂tar = tartaric acid).Their structures were determined by single-crystal X-ray diffraction analyses and further characterized by X-ray powder diffraction, elemental analyses, IR spectra and TG analyses. Compound 1 displays a 2D layer structure containing {[Zn₄(trz)₄]⁴⁺}_n layers decorated by the suc ligand. Compound 2 is in a 3D structure formed by the interconnection of 2D {[Zn₄(trz)₄]⁴⁺}_n layers with tar ligand, resulting a 3,4-connected topological network. Due to the different coordination mode and conformation of aliphatic carboxylate ligand, the similar 2D {[Zn₄(trz)₄]⁴⁺}_n layers stack in the -AAA- fashion in 1, while the {[Zn₄(trz)₄]⁴⁺}_n layers hold together in the -ABAB- stacking sequence in 2. Additionally, the two compounds show strong fluorescence in the solid state at room temperature.     

Preferential azido bridging regulating the structural aspects in cobalt(III) and copper(II)-Schiff base complexes: Syntheses, magnetostructural correlations and catalytic studies

A tridentate NNO donor Schiff base ligand [(1Z,3E)-3-((pyridin-2-yl)methylimino)-1-phenylbut-1-en-1-ol = LH] in presence of azide ions coordinates with cobalt(II) and copper(II) ions giving rise to three new coordination complexes [Co₂(L)₂(μ_1,1-N₃)₂(N₃)₂] (1), [Cu₂(L)₂(μ_1,3-N₃)]·ClO₄ (2) and [(μ_1,1-N₃)₂Cu₅(μ-OL)₂(μ_1,1-N₃)₄(μ_1,1,1-N₃)₂]_n (3). The complexes have been characterized by elemental analysis, FT-IR, UV-Vis spectral studies, and single crystal X-ray diffraction studies. These complexes demonstrate that under different synthetic conditions the azide ions and the Schiff base ligand (LH) show different coordination modes with cobalt(II) and copper(II) ions, giving rise to unusual dinuclear and polynuclear species (1, 2 and 3) whose structural variations are discussed. Magneto-structural correlation for the very rare singly μ_1,3-N₃ bridged Cu^II-Schiff base dinuclear species (2) has been studied. In addition, the catalytic properties of 1 for alkene oxidation and the general catalase-like activity behavior of 2 have been discussed.     

Coordination properties of ethyl bis(pyridin-2-ylmethyl)phosphate ligand with copper and zinc chloride. X-ray crystal structure of Cu(II) complex

A new ethyl bis(pyridin-2-ylmethyl)phosphate (2-bis(pm)Ope) ligand has been synthesized and used for synthesis of copper(II) and zinc(II) complexes of the formula [MCl₂(2-bis(pm)Ope)] [M = Cu(II), Zn(II)]. Despite having the same general formula, Cu(II) and Zn(II) complexes are not isostructural. The Zn(II) complex is four coordinated (MCl₂N₂) forming probably tetrahedral structure whereas the Cu(II) complex of distorted square pyramidal geometry is five coordinated (MCl₂ON₂). The later compound not only coordinates by two nitrogen atoms of pyridine rings but also by the oxygen atom of pyridin-2-ylmethoxyl residue. The compound (2-bis(pm)Ope) has been obtained as the product of diethyl (pyridin-2-ylmethyl)phosphate’s (2-pmOpe) transestrification. The compounds have been identified and characterized by IR, far-IR, ¹H NMR, ³¹P NMR and elemental analyses. The crystal structure of copper(II) complex i.e. [CuCl₂(2-bis(pm)Ope)] has been determined by the X-ray diffraction method. The low temperature magnetic study reveals significant antiferromagnetic interaction between copper centers through the H-bond system.     

Preparation, separation and characterisation of two regioisomers of a N-hydroxyalkylpyridylpyrazole ligand: A structural investigation of their coordination to Pd(II), Pt(II) and Zn(II) centres

The reaction of the β-diketone 1-phenyl-3-(pyridyn-2-yl)propane-1,3-dione, and the monosubstituted hydrazine 2-hydroxyethylhydrazine has been investigated. Two regioisomers were identified, 2-(3-phenyl-5-(pyridyn-2-yl)-1H-pyrazol-1-yl)ethanol (pzol.1) and 2-(5-phenyl-3-(pyridyn-2-yl)-1H-pyrazol-1-yl)ethanol (pzol.2) in 57:43 ratio. The separation of the regioisomers was done by silica column chromatography using ethyl acetate as eluent.Palladium(II) and platinum(II), [MCl₂(pzol.1)₂], [MCl₂(pzol.2)], and zinc(II), [ZnCl₂(pzol.1)], [ZnCl₂(pzol.2)] complexes were synthesised and characterised. The crystals and molecular structures of [PdCl₂(pzol.2)]·H₂O and [ZnCl₂(pzol.2)] were solved by X-ray diffraction, and consist of mononuclear complexes. In complex [PdCl₂(pzol.2)]·H₂O, the Pd(II) centre has a typical square planar geometry, with a slight tetrahedral distortion. The tetra-coordinated atom is bonded to one pyridinic nitrogen, one pyrazolic nitrogen and two chlorine atoms in cis disposition. The pzol.2 ligand acts as a bidentate chelate forming a five-membered metallocycle ring. In complex [ZnCl₂(pzol.2)], the Zn(II) is five-coordinated with two Zn-N bonds (Zn-N_pz and Zn-N_py), one Zn-OH bond and two Zn-Cl bonds. The coordination geometry is intermediate between a trigonal bipyramid and a square pyramid. In this complex, the ligand pzol.2 is tridentated and forms two metallocycle rings.     

Complexation of 2-hydroxynicotinic and 3-hydroxypicolinic acids with zinc(II). Solution state study and crystal structure of trans-diaqua-bis-(3-hydroxypicolinato)zinc(II)

The interactions between zinc(II) and the two ligands 2-hydroxynicotinic acid (HNic) and 3-hydroxypicolinic acid (HPic) have been investigated by means of potentiometric titrations in aqueous 0.6 m (Na)Cl at 25 °C. In both cases, only mononuclear complexes are formed. The qualitative and quantitative results obtained have been confirmed in part by UV-Vis spectrophotometry and ¹H NMR spectroscopy. The complex trans-diaqua-bis-(3-hydroxypicolinato)zinc(II) was obtained as a crystal and examined by X-ray crystallography. The thermodynamic results allow drawing some conclusions regarding the extent of Zn(II) interference in a hypothetical chelation therapy treatment of aluminium or iron overload with these two ligands.     

Synthesis and crystal structure of one-dimensional zinc(II) polymer constructed by salicylate and trans-1,2-bis(4-pyridyl)ethylene

A new zinc(II) compound, [Zn₂(Hsal)₄(4,4′-bpe)₂] · [Zn(Hsal)₂(4,4′-bpe)(DMF)(H₂O)] · CH₃OH (1) (Hsal = salicylate and 4,4′-bpe = trans-1,2-bis(4-pyridyl)ethylene) has been synthesized and characterized by elemental analysis, infrared spectroscopy, thermogravimetric analysis, and single crystal X-ray diffraction. The crystal structure consists of three independent moieties: [Zn₂(Hsal)₄(4,4′-bpe)₂], [Zn(Hsal)₂(4,4′-bpe)(DMF)(H₂O)], and non-coordinated CH₃OH molecule. In the compound two independent moieties which are connected by 4,4′-bpe to form 1-D chains, respectively, are further expended to accomplish 2-D network through hydrogen-bonding interactions between non-coordinated methanol and coordinated water molecule or carboxylate oxygen atoms of Hsal ligands.     

Crystal structure of zinc citrate

The crystal structure of zinc citrate [Zn(II) (C₆H₅O₇)₂·4NH₄⁺] shows isolated zinc ions octahedrally coordinated to two equivalent citrates via a central hydroxyl, central carboxyl, and one terminal carboxyl from each citrate. The clusters are linked through hydrogen bonds to ammonium ions in the lattice. The structure is distinctly different from that of other divalent cation triply ionized citrate complexes, which are polymeric. Crystal data : space group P2₁/C, a = 8.784(3) Å, b = 13.499(4) Å, c = 9.083(3) Å, β = 113.4°(1), V = 988(1) ų. Citrate has been identified as the low molecular weight ligand that complexes zinc in human milk; this may be of interest in relation to intestinal zinc absorption.     

Metal complexes of cyclic hydroxamates. Synthesis and crystal structures of 3-hydroxy-2-methyl-3H-quinazolin-4-one (ChaH) and of its Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) complexes

The attempted acetylation of anthranilic hydroxamic acid (2-aminobenzohydroxamic acid) as a possible dual inhibitor of the catalytic sites in prostaglandin-H-synthase (PGHS) gave the cyclic hydroxamic acid 3-hydroxy-2-methyl-3H-quinazolin-4-one (ChaH) which was characterised by spectroscopy and X-ray crystallography. The length of the hydroxamic acid C-N bond, 1.3998(17) Å, in ChaH is longer than normal (∼1.33 Å) indicative of reduced delocalisation of the nitrogen lone pair of electrons into the hydroxamic acid π system. This is confirmed by the appearance of the ν(CO) band at a considerably higher wavenumber in the IR spectrum than normal. The complexes Fe(Cha)₂(Cl)(H₂O)·⁷/₂H₂O, Co(Cha)₂(EtOH)₂, Ni(Cha)₂(EtOH)₂, Cu(Cha)(H₂O)(Cl) and Zn(Cha)₂(H₂O), have been synthesised and their structures determined by X-ray crystallography. The X-ray data confirmed coordination by Cha^- through the carbonyl and deprotonated hydroxamate oxygen in all cases. The M-O (hydroxamate) bonds are shorter than the M-O (carbonyl) bonds by between 0.0930 Å for the Co(II) complex and 0.0448 Å for the Ni(II) complex. The geometries of all complexes conform to the coordination requirements of the particular metal ion involved. Speciation studies for ChaH and its complexes with Ni(II) and Zn(II) were carried out using pH-metric methods. The results show that ChaH is much more acidic than related acyclic hydroxamic acids and that its metal complexes are correspondingly less stable.     

On the possible roles of N-terminal His-rich domains of Cu,Zn SODs of some Gram-negative bacteria

The Cu,Zn superoxide dismutases (Cu,Zn SOD) isolated from some Gram-negative bacteria possess a His-rich N-terminal metal binding extension. The N-terminal domain of Haemophilus ducreyi Cu,Zn SOD has been previously proposed to play a copper(II)-, and may be a zinc(II)-chaperoning role under metal ion starvation, and to behave as a temporary (low activity) superoxide dismutating center if copper(II) is available. The N-terminal extension of Cu,Zn SOD from Actinobacillus pleuropneumoniae starts with an analogous sequence (HxDHxH), but contains considerably fewer metal binding sites. In order to study the possibility of the generalization of the above mentioned functions over all Gram-negative bacteria possessing His-rich N-terminal extension, here we report thermodynamic and solution structural analysis of the copper(II) and zinc(II) complexes of a peptide corresponding to the first eight amino acids (HADHDHKK-NH₂, L) of the enzyme isolated from A. pleuropneumoniae. In equimolar solutions of Cu(II)/Zn(II) and the peptide the MH₂L complexes are dominant in the neutral pH-range. L has extraordinary copper(II) sequestering capacity (K_D,Cu = 7.4 × 10^− 13 M at pH 7.4), which is provided only by non-amide (side chain) donors. The central ion in CuH₂L is coordinated by four nitrogens {NH₂,3N_im} in the equatorial plane. In ZnH₂L the peptide binds to zinc(II) through a {NH₂,2N_im,COO⁻} donor set, and its zinc binding affinity is relatively modest (K_D,Zn = 4.8 × 10^− 7 M at pH 7.4). Consequently, the presented data do support a general chaperoning role of the N-terminal His-rich region of Gram-negative bacteria in copper(II) uptake, but do not confirm similar function for zinc(II). Interestingly, the complex CuH₂L has very high SOD-like activity, which may further support the multifunctional role of the copper(II)-bound N-terminal His-rich domain of Cu,Zn SODs of Gram-negative bacteria. The proposed structure for the MH₂L complexes has been verified by semiempirical quantum chemical calculations (PM6), too.     

Formation of coordination polymer and molecular complex of 4,4′-bipyridyl-N,N′-dioxide of manganese and zinc

A 1D-coordination polymer [{Mn₃(C₆H₅COO)₆(BPNO)₂(MeOH)₂}(MeOH)₂]_n (1) having benzoate as the anionic ligand and 4,4′-bipyridyl-N,N′-dioxide (BPNO) as bridging ligand is synthesized by reacting benzoic acid with manganese(II) acetate tetrahydrate followed by reaction with 4,4′-bipyridyl-N N′-dioxide. The bridging bidentate BPNO ligands in this coordination polymer along with the benzoate bridges hold the repeated units. The chain like structure in one dimension by benzoate bridges are connected to each other through the μ³-η²:η¹ bridges of BPNO ligands. This coordination polymer can be transformed to a molecular complex [Mn(H₂O)₆](C₆H₅COO)_2.4BPNO (2). In this complex the BPNO remains outside the coordination sphere but they are hydrogen bonded to water molecules to form self assembled structure. The reaction of 3,5-pyrazoledicarboxylic acid (L₁H2) and BPNO with manganese(II) acetate or zinc(II) acetate led to molecular complexes with composition [M₂(L₁)₂(H₂O)₆].BPNO·xH₂O {where M = Mn(II) (3), Zn(II)(4)}. These molecular complexes of BPNO are characterised by X-ray crystallography. The complexes 3-4 are binuclear carboxylate complexes having M₂O₂ core formed from carboxylate ligands with two metal ions.     

Synthesis,characterization and bioactivity of four novel trinuclear copper(II) and nickel(II) complexes with pentadentate ligands derived from N-acylsalicylhydrazide

Four novel trinuclear copper(II)/nickel(II) complexes with four trianionic pentadentate ligands, N-(3-t-butylbenzoyl)-5-nitrosalicylhydrazide (H₃3-t-bbznshz), N-(3,5-dimethylbenzoyl)salicylhydrazide (H₃3,5-dmbzshz), N-(phenylacetyl)-5-bromosalicylhydrazide (H₃pabshz) and N-(3-t-butylbenzoyl)salicylhydrazide (H₃3-t-bbzshz) have been synthesized and characterized by X-ray crystallography. These trinuclear compounds all have an M–N–N–M–N–N–M core formed by three metal ions and two ligands. The geometries of three Cu(II) ions in compound Cu₃(3-t-bbznshz)₂(H₂O)(DMF)(py)₂ · DMF (1) alternate between distorted square pyramidal and square planar, while in compound Cu₃(3,5-dmbzshz)₂(py)₂ (2), they are all square planar. Three Ni(II) ions in compound Ni₃(pabshz)₂(DMF)₂(py)₂ (3) and Ni₃(3-t-bbzshz)₂(py)₄ · 2H₂O (4) follow square-planar/octahedral/square-planar coordination geometry. Compounds 1, 2 and 4 are bent trinuclear, with the bend angles of 156.4°, 141.49° and 127.1°, respectively, while the three nickel ions in compound 3 are strictly linear, with an angle of 180°. Studies on the trinuclear Ni(II) complexes show that the β-branched N-acylsalicylhydrazide ligands with sterically flexible Cα methylene groups are easier to yield linear trinuclear Ni(II) complexes, while α-branched N-acylsalicylhydrazides ligands tend to form bent trinuclear Ni(II) complexes. Antibacterial screening data indicate that the trinuclear Cu(II) compound 2 is more active than 1 and mononuclear Cu(II) compound, bent trinuclear Ni(II) compound 4 is more active than linear compound 3 and less active than tetranuclear nickel compound in the previous study.