Dieter Rehder

The coordination chemistry of vanadium as related to its biological functions

Abstract The binding of vanadium to protein side-chains such as provided by tyrosinate, serinate, aspartate, glutamate, cysteinate, methionine and histidine is modelled by complexes with ligand sets containing phenolate, alkoxide, carboxylate, thiolate, thioether and enamine functions. The complexes mimic possible intermediates and structural motifs of the coordination environment of vanadium in vanadium–nitrogenase, vanadate-dependent haloperoxidases, the interaction with phosphorylation enzymes, and the redox-interaction with cysteinyl residues. The solid state investigations are supplemented by solution studies on vanadate–dipeptide and vanadate–adenosine systems, based on combined 51 V-NMR and potentiometric measurements. Model reactions for the function of haloperoxidases and vanadium–nitrogenase (including the alkyne–reductase and isonitrile–reductase/ligase activities) are described, and the impact of these investigations for corresponding in vitro applications is dealt with. The relevance of catecholatovanadium complexes for the accumulation of vanadium by ascidians is also addressed.

Biological and medicinal aspects of vanadium

Abstract The importance of vanadium in life processes is addressed, emphasising the vanadium cofactors in vanadate-dependent haloperoxidases and vanadium-nitrogenases. Structural and functional model compounds for these enzymes are introduced, and the use of haloperoxidase models in the enantioselective oxygenation of thioethers is discussed. Specific attention is given to the redox interaction on the one hand, and stabilisation by coordination on the other hand, in the systems vanadium(III, IV and V) plus (bio-related) thiofunctional compounds, since these interactions should be of some importance in vanadium speciation under physiological conditions. With respect to the medicinal potential of vanadium compounds, their insulin-mimetic behaviour and hence efficacy in the oral treatment of both forms of diabetes mellitus is extemporated.

The medicinal and catalytic potential of model complexes of vanadate-dependent haloperoxidases

Abstract Vanadium(V) complexes predominantly of composition VO( O 3 N ), modeling the active center of vanadate-dependent haloperoxidases, are investigated with respect to (i) their catalytic potential in enantio-selective oxidation by peroxide of prochiral sulfides, and (ii) their in vitro cytotoxicity and insulin-mimetic ability towards fibroblast cell cultures. The peroxidation of methyl-tolylsulfide with cumyl-hydroperoxide, which is related to the sulfideperoxidase activity of haloperoxidases, is catalyzed by ( RRR )-[VO(OMe)L] [H 2 L=( R , R )-bis(2-phenylethanol)-( R )-1-phenylethylamine] as well as by a mixture of [VO(O i Pr) 3 ] and H 2 L to an enantiomeric excess (ee) of 25%. The crystal and molecular structures of ( RRR )-[VO(OMe)L] · 1/2MeOH are reported. In the context of the phosphatase activity of the apo-haloperoxidases, possible modes of action of vanadium compounds in insulin-mimesis are addressed. In vitro results for seven oxovanadium(IV) and -(V) coordination compounds show that, at essentially non-toxic concentrations [ c (V)

Interactions of oxovanadium(IV) and the quinolone family member--ciprofloxacin.

The interactions of quinolone ciprofloxacin (cfH) and oxovanadium(IV) were studied by various methods. Green crystals of a complex [V(IV)O(cf)(2)(H(2)O)] were isolated and the molecular connectivities established, although the crystal structure was not perfectly refined due to the instability of the crystals. Based on a plausible interpretation of the data sets, two cf anions bidentately coordinate to a vanadyl cation through carboxylate and carbonyl oxygen atoms; in addition, there is a water molecule in the coordination sphere. Solution techniques (cyclic voltammetry, electronic and electron paramagnetic resonance spectroscopy, potentiometric measurements) confirmed the presence of various species in the solution, the composition of which strongly depends on the conditions in the system. The antibacterial activity of the complex against various microorganisms was tested and it was established that its activity is similar to that of free ciprofloxacin.

Synthesis, characterisation, reactivity and in vitro antiamoebic activity of hydrazone based oxovanadium(IV), oxovanadium(V) and µ-bis(oxo)bis{oxovanadium(V)} complexes

Binuclear, mu-bis(oxo)bis{oxovanadium(V)} complexes [(VOL)2(mu-O)2](2 and 7)(where HL are the hydrazones Hacpy-nah I or Hacpy-fah II; acpy = 2-acetylpyridine, nah = nicotinic acid hydrazide and fah = 2-furoic acid hydrazide) were prepared by the reaction of [VO(acac)2] and the ligands in methanol followed by aerial oxidation. The paramagnetic intermediate complexes [VO(acac)(acpy-nah)](1) and [VO(acac)(acpy-fah)](6) have also been isolated. Treatment of [VO(acac)(acpy-nah)] and [VO(acac)(acpy-fah)] with aqueous H2O2 yields the oxoperoxovanadium(V) complexes [VO(O2)(acpy-nah)](3) and [VO(O2)(acpy-fah)](8). In the presence of catechol (H2cat) or benzohydroxamic acid (H2bha), 1 and 6 give the mixed chelate complexes [VO(cat)L](HL =I: 4, HL =II: 9) or [VO(bha)L](HL =I: 5, HL =II: 10). Complexes 4, 5, 9 and 10 slowly convert to the corresponding oxo-mu-oxo species 2 and 7 in DMF solution. Ascorbic acid enhances this conversion under aerobic conditions, possibly through reduction of these complexes with concomitant removal of coordinated catecholate or benzohydroxamate. Acidification of 7 with HCl dissolved in methanol afforded a hydroxo(oxo) complex. The crystal and molecular structure of 2.1.5H2O has been determined, and the structure of 7 re-determined, by single crystal X-ray diffraction. Both of these binuclear complexes contain the uncommon asymmetrical {VO(mu-O)}2 diamond core. The in vitro tests of the antiamoebic activity of ligands I and II and their binuclear complexes 2 and 7 against the protozoan parasite Entamoeba histolytica show that the ligands have no amoebicidal activity while their vanadium complexes 2 and 7 display more effective amoebicidal activity than the most commonly used drug metronidazole (IC50 values are 1.68 and 0.45 microM, respectively vs 1.81 microM for metronidazole). Complexes 2 and 7 catalyse the oxidation of styrene and ethyl benzene effectively. Oxidation of styrene, using H2O2 as an oxidant, gives styrene epoxide, 2-phenylacetaldehyde, benzaldehyde, benzoic acid and 1-phenyl-ethane-1,2-diol, while ethyl benzene yields benzyl alcohol, benzaldehyde and 1-phenyl-ethane-1,2-diol.

Structure and function of vanadium compounds in living organisms.

Vanadium has been recognized as a metal of biological importance only recently. In this mini-review, its main functions uncovered during the past few years are addressed. These encompass (i) the regulation of phosphate metabolizing enzymes (which is exemplified for the inhibition of ribonucleases by vanadate), (ii) the halogenation of organic compounds by vanadate-dependent non-heme peroxidases from seaweeds, (iii) the reductive protonation of nitrogen (nitrogen fixation) by alternative, i.e. vanadium-containing, nitrogenases from N2-fixing bacteria, (iv) vanadium sequestering by sea squirts (ascidians), and (v) amavadine, a low molecular weight complex of V(IV) accumulated in the fly agaric and related toadstools. The function of vanadium, while still illusive in ascidians and toadstools, begins to be understood in vanadium-enzyme interaction. Investigations into the structure and function of model compounds play an increasingly important role in elucidating the biological significance of vanadium.

A water-soluble, neutral {aqua-VV}2 complex with a biomimetic ONO ligand set

Abstract The water-soluble complex [{VO(van-L-ser)H2O}2μ-O], where van-L-ser is the Schiff base formed from o-vanillin and L-serine, has been prepared and structurally characterised. Characteristics, including the hydrogen bonding network, are addressed in the context of biologically relevant vanadium compounds.

A Potentiometric and51V NMR Study of the Aqueous H+/H2VO4−/H2O2/L-α-Alanyl-L-histidine System

The speciation in the quaternary aqueous H+/H2VO4−/H2O2/L-α-alanyl-L-histidine (Ah) system has been determined from quantitative 51V NMR measurements and potentiometric data (glass electrode). The study was performed in 0.150 M Na(Cl) medium at 25 °C. Data were evaluated with the computer program LAKE, which is able to treat combined EMF and NMR data. The pKa values for Ah were determined as 8.06, 6.72 and 2.64. In the ternary H+/H2VO4−/Ah system, two complexes, (H+)p(H2VO4−)q(Ah)r, for which (p, q, r) values of (0, 1, 1) and (1, 1, 1) with log β0,1,1=2.52±0.03 and log β1,1,1=9.40±0.05 (pKa=6.88), respectively, explain all data. The errors given are 3σ. In the quaternary H+/H2VO4−/H2O2/Ah system, eight complexes were determined in addition to all binary and ternary complexes, four with a V/X/Ah ratio 1:1:1 and four with a ratio 1:2:1 (X=peroxo ligand). VX2Ah2− and VX2Ah− (pKa=8.19) are the main complexes and predominate in the pH range 5 to 9. Three additional minor species have also been found but their compositions could not be determined owing to their small amounts. Equilibria are slow, significant decomposition of peroxide occurs only in acidic solutions. Data in the pH range 5 to 10 have been used for the LAKE calculations. Chemical shifts, compositions, and formation constants for the eight quaternary complexes are given, and equilibrium conditions are illustrated in distribution diagrams. Structural proposals for VX2Ah2− and VX2Ah− are made from 1H and 13C NMR measurements.

A spherical 24 butyrate aggregate with a hydrophobic cavity in a capsule with flexible pores: confinement effects and uptake-release equilibria at elevated temperatures.

Compounds like zeolites exhibiting nanoscale holes and channels can serve as filters and traps or hosts for molecular guests. They play an important role in many areas of chemistry and materials science as they can be used for different tasks, for example, for separation and storage purposes. 2] Our related interest concerns molecular (i.e., discrete) porous metal oxide based capsule analogues, which specifically allow encapsulation of a large number of different guests; for general remarks regarding inorganic host–guest chemistry, see Ref. [3]. It was our aim to integrate within a capsule s cavity an unprecedented structurally well-defined, mostly hydrophobic aggregate. This goal was achieved with a robust, spherical, porous capsule of the type [{pentagon}12{linker}30] [{(Mo)Mo5O21(H2O)6}12{Mo2O4(ligand)}30] [4–7] allowing, generally speaking, a wide range of applications. 8] The capsules interiors can be modified by introducing a variety of species coordinating weakly to the 30 dinuclear {Mo2} linkers. This approach has now allowed, as intended, the encapsulation of the quasi-spherical, partly compact 24butyrate aggregate, whose constituents show under the confined conditions interesting interactions (an attractive, up-to-date research field) detectable by ROESY NMR spectroscopy in agreement with the related distances. Remarkably, the present scenario automatically generates an unprecedented hydrophobic cavity and shell at the center of the capsule that is spanned by 72 H atoms originating from 24 butyrate CH3 groups. Furthermore, the resulting capsule skeleton is stable even at rather high temperatures, which allows the observation of a strong uptake–release exchange of the butyrates with the future option to introduce into the capsule system different species that can react with one another under confined conditions. The pictorial title “flexible” refers to one of the important properties of the capsules, that is, the option of reversible pore widening, which will be discussed in comparison with formally related scenarios of spherical viruses. Compound 1 containing the capsule 1 a loaded with the 24butyrate aggregate (Figure 1) is obtained by the reaction of an aqueous solution of heptamolybdate with hydrazinium sulfate (as reducing agent) and butyric acid and a subsequent recrystallization process. (The product s recrystallization was primarily performed to obtain higher-quality crystals.) This synthetic procedure is similar to that which led to the first published related capsule-type compound with 30 acetate ligands obtained in a facile high-yield synthesis, while the

Polyoxovanadates with Organic Ligands

Polyoxovanadates are inhibitors to various phosphate-metabolizing enzymes. The question arises of how the cluster is bound to the protein matrix. This paper describes oxovanadates with carboxylate and hydroxide ligands in the periphery of the cluster, which may be considered to model oxovanadate binding to carboxylic and alcoholic side-chain functions of the protein. Examples for complexes carrying alkoxo ligands dealt with in this article are dinuclear vanadate(V) esters, and hexa-, octa-and decanuclear, mixed-valence (VV/VIV) clusters, the latter related to decavanadate. The possible role of dimeric vanadate esters as transition state anologues in enzymatic phosphoester cleavage is addressed. Examples for carboxylate complexes are the mononuclear, seven-coordinate mixed anhydride between orthovanadic acid and pivalic acid, containing the carboxylate in the bidentate mode, tetra-, penta-and hexanuclear VIV/VV clusters with bridging carboxylate, and trinuclear VIV and VII/VIII clusters, bridged by carboxylates and trebly bridged by O2-. Special attention is given to a comparison of the bowls containing a V4(µ-O)3(µ-OH)(O2CR)4 and V4(µ-O4(O2CR)4 core, respecitvely, which can accomodate a K+ or a NO3 -. 51V NMR spectroscopy is shown to be a useful tool, in many cases, for the vanadium speciation of complex systems.