Agnete la Cour

Chloro-substituted dipicolinate vanadium complexes: synthesis, solution, solid-state, and insulin-enhancing properties.

Three vanadium complexes of chlorodipicolinic acid (4-chloro-2,6-dipicolinic acid) in oxidation states III, IV, and V were prepared and their properties characterized across the oxidation states. In addition, the series of hydroxylamido, methylhydroxylamido, dimethylhydroxylamido, and diethylhydroxylamido complexes were prepared from the chlorodipicolinato dioxovanadium(V) complex. The vanadium(V) compounds were characterized in solution by (51)V and (1)H NMR and in the solid-state by X-ray diffraction and (51)V NMR. Density Functional Theory (DFT) calculations were performed to evaluate the experimental parameters and further describes the electronic structure of the complex. The small structural changes that do occur in bond lengths and angles and partial charges on different atoms are minor compared to the charge features that are responsible for the majority of the electric field gradient tensor. The EPR parameters of the vanadium(IV) complex were characterized and compared to the corresponding dipicolinate complex. The chemical properties of the chlorodipicolinate compounds are discussed and correlated with their insulin-enhancing activity in streptozoticin (STZ) induced diabetic Wistar rats. The effect of the chloro-substitution on lowering diabetic hyperglycemia was evaluated and differences were found depending on the compounds oxidation state similar as was observed for the vanadium III, IV and V dipicolinate complexes (P. Buglyo, D.C. Crans, E.M. Nagy, R.L. Lindo, L. Yang, J.J. Smee, W. Jin, L.-H. Chi, M.E. Godzala III, G.R. Willsky, Inorg. Chem. 44 (2005) 5416-5427). However, a linear correlation of oxidation states with efficacy was not observed, which suggests that the differences in mode of action are not simply an issue of redox equivalents. Importantly, our results contrast the previous observation with the vanadium-picolinate complexes, where the halogen substituents increased the insulin-enhancing properties of the complex (T. Takino, H. Yasui, A. Yoshitake, Y. Hamajima, R. Matsushita, J. Takada, H. Sakurai, J. Biol. Inorg. Chem. 6 (2001) 133-142).

Zinc(II) N2S2 Schiff-base complexesincorporating pyrazole: syntheses, characterization, tautomeric equilibriaand racemization kinetics

Chiral four-co-ordinate zinc(II) N 2 S 2 complexes with bi- or tetra-dentate Schiff-base ligands have been prepared and their properties investigated by spectroscopic methods. The single-crystal structures have been determined for two different crystalline modifications of bis[4-(2,6-dimethylphenyliminomethyl)-1-methyl-3-phenylpyrazole-5- thiolato-N,S]zinc(II) 1, a triclinic modification (1a) and an orthorhombic one (1b), and for bis(4-isopropyliminomethyl-3-methyl-1-phenylpyrazole-5-thiolato-N ,S)zinc(II) 2. The co-ordination geometry of 1 is similar to that found for the active site of horse liver alcohol dehydrogenase. The asymmetric units in the structures of 1 contain two pseudo-tetrahedral complexes slightly distorted towards trans-planar co-ordination geometries; the angles θ between the N–Zn–S and S′–Zn–N′ planes are 97.0 and 96.8 (modification 1a), 92.5 and 98.6 ° (1b) for the two molecules, respectively. The structure of 2 also reveals a pseudo-tetrahedral geometry and a slight distortion towards a cis-planar co-ordination (θ = 82.63°) typical of M II N 2 S 2 complexes. The racemization kinetics for the process Δ Λ have been investigated for four complexes by temperature-dependent 1 H NMR spectroscopy and the activation parameters derived for complexes 1 [ΔH ‡ = 80.7 kJ mol -1 , ΔS ‡ = -2.9 J K -1 mol -1 , ΔG ‡ (25 °C) = 81.6 kJ mol -1 ] and 2 [ΔH ‡ = 67.2 kJ mol -1 , ΔS ‡ = -57.8 J K -1 mol -1 , ΔG ‡ (25 °C) = 84.4 kJ mol -1 ]. The complexes carrying tetradentate ligands do not racemize below 90 °C. The tautomeric equilibria for the protonated pro-ligands and the preferred mesomer of the complexes have been investigated by NMR and UV spectroscopy. The pro-ligands are mainly in the thione form, while the ligands are thiolate-like when co-ordinated to zinc(II). The evolution of the electronic spectra with time, however, reveals the development of thiol- or thiolate-like forms for both pro-ligands and complexes.

Diaqua­bis{3‐methyl‐1‐phenyl‐4‐[(E)‐phen­yl(phenyl­iminio)meth­yl]‐1H‐pyrazol‐5‐olato‐κ2O,N4}nickel(II) dimethyl sulfoxide disolvate

3-Methyl-1-phenyl-4-[(E)-phenyl(phenyliminio)methyl]-1Hpyrazol-5-olate (L) reacts with nickel(II) acetate to give a complex [Ni(L)2(H2O)2] 2(CH3)2SO, (I). The structure of complex (I) together with that of the free ligand was described briefly on a poster (Anderson et al., 1999). The structures of metal complexes with ligands in which the phenyl group on the imino N of L is replaced by PhOCMe in Cu(L)2 H2O (Wang et al., 2003), naphthyl in Co(L)2(DMF)2 (Zhang et al., 2004) and PhCl in Co(L)2 (Li & Yang, 2004) have been reported. The structure of the free ligand L has been described by Parsons et al. (2004) who found essentially the same structure as that found by us (la Cour & Hazell, 2006).

Tetrakis[μ-1,3-bis(4-methyl-2-pyridylimino)isoindolinato]trimercury(II) dinitrate methanol tetrasolvate

The title compound, [Hg (C H N ) ](NO ) ·4CH OH, consists of a trinuclear Hg dipositive cation, [Hg (4′-Me ) ] , two nitrate anions and four occluded methanol molecules. The Hg atoms of the cation lie on a crystallographic twofold axis and are tetrahedrally coordinated by nitrogen-donor atoms of the bridging 1,3-bis(4-methyl-2-pyridylimino)isoindoline ligands. The central Hg atom is coordinated by four pyridine N atoms, one from each of the 4′-Me ligands, while the two outer Hg atoms are each coordinated by two pyridine and two pyrrole N atoms.

Racemization kinetics and spin states of four-co-ordinatenickel(II) N2X2 Schiff-base and azacomplexes with bi- or tetra-dentate ligands incorporating pyrazole(X = NH or S)

Bis(bidentate ligand) and tetradentate ligand nickel(II) N 2 X 2 Schiff-base and aza complexes (X = NH or S) have been prepared and their properties investigated by spectroscopic methods. In the bis(bidentate ligand) complexes the aza function stabilizes the low-spin S = 0 state compared with the imine function. The aza complexes are low spin both in the solid state and in solution; the Schiff-base complexes are either low or high spin (S = 1) in the solid state, and are either in spin equilibrium (S = 0 ⇌ S = 1) or high spin in solution. The crystal structure has been solved for the high-spin complex bis(4-isopropyliminomethyl-1,3-diphenylpyrazol-5-ylaminato)nickel( II). The co-ordination of Ni is pseudo-tetrahedral, the angle between the N–Ni–NH and NH′–Ni–N′ planes being 93.8(1)°. The Ni–N (imine) bond lengths are 1.999(2) and 2.003(3) A, significantly longer than the Ni–N (amine) bond lengths of 1.919(2) A. In the tetradentate ligand complexes the two identical halves of the ligands are linked by aliphatic four-carbon chains. When the linkage is CMe 2 (CH 2 ) 2 CMe 2 the complexes are fully paramagnetic in the solid state and in solution, while complexes bridged by unsubstituted (CH 2 ) 4 are low spin in the solid state and in spin equilibrium in solution. The crystal structure of [N,N′-bis(1,3-dimethyl-5-sulfanylpyrazol-4- ylmethylene)butane-1,4-diaminato]nickel(II) reveals an almost planar co-ordination geometry, the angle between the N–Ni–S and S′–Ni–N′ planes being 7.9(3)°. The Schiff-base complexes are chiral and all show evidence of racemization in solution. Thermodynamic parameters for the spin-equilibrium process in CD 2 Cl 2 [ΔG(25 °C) from -4.32 to 0.71 kJ mol -1 for the bis(bidentate ligand) systems, from 3.72 to 11.3 kJ mol -1 for the tetradentate ligand systems] and kinetic parameters for the racemization process in CD 2 Cl 2 or CDCl 2 CDCl 2 [ΔG ‡ (25 °C) from 40.5 to 53.3 kJ mol -1 for the bis(bidentate ligand) complexes, 46.5 to 63.1 kJ mol -1 for the tetradentate ligand complexes] have been derived using variable-temperature 1 H NMR spectroscopy. Sulfur donor atoms and aryl substituents favour the low-spin state. Ligand-field parameters for the Schiff-base complexes have been derived from the electronic spectra.

Metal(II) N2S2 Schiff-base complexesincorporating pyrazole or isoxazole (M = Ni, Cu or Zn). Spinstates, racemization kinetics and electrochemistry

Schiff-base complexes incorporating a five-membered aromatic heterocycle (isoxazole or pyrazole) and biologically important 3d metal(II) ions (M = Ni, Cu or Zn) have been synthesized. The crystal structures have been determined for [N,N′-bis(3-phenyl-5-sulfanylisoxazol-4- ylmethylene)butane-1,4-diaminato]copper(II) 1b and for [N,N′-bis(1-methyl-3-phenyl-5-sulfanylpyrazol-4- ylmethylene)butane-1,4-diaminato]nickel(II) 2a. In both structures the metal atom is co-ordinated to two nitrogen and to two sulfur atoms which form a flattened tetrahedron with the dihedral angles between the two N–M–S planes being 48.6(1) and 12.7(1)° respectively. Their physicochemical properties have been studied in solution. The spin-equilibrium process S = 0 S = 1 and the racemization process Δ Λ for the nickel(II) complexes have been investigated by temperature-dependent 1 H NMR spectroscopy. Complex 2a (ΔG = 7.8 kJ mol -1 at 25 °C) is more stabilized in the low-spin state than is 1a (ΔG = 3.2 kJ mol -1 ). The racemization rates are 2.3 × 10 4 and 1.7 × 10 4 s -1 at 25 °C for 1a and 2a, respectively. The stereochemistry of the zinc(II) and copper(II) complexes in solution seems to be independent of the ligand. For the former the configurations were evaluated from the chemical shift differences between diastereotopic protons. For the latter structural similarities are seen in the electronic and ESR spectra. The electrochemical properties have been investigated by cyclic voltammetry. The isoxazole ligand stabilizes a high potential for the M II –M I reduction (E ½ ≈ 0 for Cu) compared with the pyrazole ligand (E ½ = -407 mV for Cu).

Nickel(II) N2O2 Schiff-base complexes incorporating pyrazole: syntheses, characterization and acidity of the metal centre towards co-ordinating solvents

A series of four-co-ordinate nickel(II) complexes have been prepared containing a tetradentate N2O2 aldimine or ketoimine Schiff-base ligand formed by condensation of 4-formyl-5-hydroxy- or 4-benzoyl-5-hydroxypyrazoles with aliphatic diamines containing two or three carbon atoms (n= 2 or 3). In non-donor solvents the low-spin (S= 0) state is favoured. The complexes with n= 2 are fully diamagnetic; the spin-equilibrium process (S= 0)⇌(S= 1) is, however, induced when n= 3. The crystal structure has been determined of {N,N′-bis[(5-hydroxy-1,3-diphenylpyrazolyl)phenylmethylene]propane-1,3-diaminato}nickel(II)1a which has a flattened tetrahedral geometry, and the spin-equilibrium process has been investigated for selected complexes by spectroscopic methods [ΔH 16–21 kJ mol–1, ΔS 2–22 J K–1 mol–1, and ΔG(50 °C) 14–19 kJ mol–1]. The four-co-ordinate complexes reversibly increase their co-ordination numbers in donor solvents (all) or by molecular association in non-donor solvents (the aldimine complexes only). Solid six-co-ordinate products from the reactions with dimethylsulfoxide (dmso), pyridine and water have been isolated, and the crystal structures determined of the product (1b) from the reaction of 1a with dmso and of that (3b) from the reaction of {N,N′-bis[(5-hydroxy-1,3-diphenylpyrazolyl)(p-tolyl)methylene]propane-1,3-diaminato}nickel(II) with dmso. Complexes 1b and 3b have trans distorted-octahedral geometries with O-bound dmso molecules in axial positions. The adduct formation with dmso [–ΔH 10–27 kJ mol–1, –ΔS 57–107 J K–1 mol–1, ΔG(25 °C) 0.9–7.0 kJ mol–1] and with pyridine [ΔG(25 °C)– 19 kJ mol–1] has been investigated for selected complexes by spectroscopic methods. Angular overlap model ligand-field parameters have been derived from the electronic absorption spectra.