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Amine-templated linear vanadium sulfates with different chain structures.

Amine-templated vanadium sulfates of the formula [HN(CH(2))(6)NH][(V(IV)O)(2)(OH)(2)(SO(4))(2)].H(2)O, I, [H(3)N(CH(2))(2)NH(3)][V(III)(OH)(SO(4))(2)].H(2)O, II, and [H(2)N(CH(2))(4)NH(2)][(V(IV)O)(H(2)O)(SO(4))(2)], III, have been prepared under hydrothermal conditions. These vanadium sulfates add to the new emerging family of organically templated metal sulfates. Compound I has a linear chain structure consisting of V(2)O(8) square-pyramid dimers connected by corner-sharing SO(4) tetrahedra, creating four-membered rings along the chain. Both II and III possess simple linear chain topologies formed by VO(6) octahedra and SO(4) tetrahedra, with II having the tancoite chain structure. Compound I crystallizes in the triclinic space group P1 (No. 2) with a = 7.4852(4) A, b = 9.5373(5) A, c = 11.9177(6) A, alpha = 77.22 degrees, beta = 76.47(2) degrees, gamma = 80.86 degrees, Z = 2. Compound II: monoclinic, space group P2(1)/c (No. 14), a = 6.942(2) A, b = 10.317(3) A, c = 15.102(6) A, beta = 90.64(4) degrees, Z = 4. Compound III: triclinic, space group P1 (No. 2) with a = 6.2558(10) A, b = 7.0663(14) A, c = 15.592(4) A, alpha = 90.46(2) degrees, beta = 90.47(2) degrees, gamma = 115.68(2) degrees, Z = 2. Magnetic susceptibility measurements reveal weak antiferromagnetic interactions in I and III and ferromagnetic interactions in II.

Journal Article↗

In vivo evidence of free radical formation in the rat lung after exposure to an emission source air pollution particle.

Exposure to air pollution particles can be associated with increased human morbidity and mortality. The mechanism(s) of lung injury remains unknown. We tested the hypothesis that lung exposure to oil fly ash (an emission source air pollution particle) causes in vivo free radical production. Electron spin resonance (ESR) in conjunction with the spin trap alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN) was used to detect radical adducts. Rats were instilled with 500 micrograms of either oil fly ash or saline. Twenty-four hours later, ESR spectroscopy of the chloroform extract from lungs of animals exposed to the oil fly ash gave a spectrum consistent with a carbon-centered radical adduct (hyperfine coupling constants alpha N = 15.0 G and alpha H beta = 2.5 G), while those spectra from lungs instilled with saline revealed a much weaker signal. This signal was reproduced by instilling animals with the soluble fraction of the oil fly ash, which contains soluble metal compounds. The same signal was observed after instillation of either a mixture of vanadium, nickel, and iron sulfates or VOSO4 alone. We conclude that, after instillation of an air pollution particle in the rat, ESR analysis of lung tissue demonstrates in vivo free radical production. This generation of free radicals appears to be associated with soluble metals in the oil fly ash.

Air Pollution↗

Vanadate induces p53 transactivation through hydrogen peroxide and causes apoptosis.

Vanadium is a metal widely distributed in the environment. Although vanadate-containing compounds exert potent toxic effects on a wide variety of biological systems, the mechanisms controlling vanadate-induced adverse effects remain to be elucidated. The present study investigated the vanadate-induced p53 activation and involvement of reactive oxygen species (ROS) in p53 activation as well as the role of p53 in apoptosis induction by vanadate. Exposure of mouse epidermal JB6 cells to vanadate led to transactivation of p53 activity in a time- and dose-dependent manner. It also caused mitochondrial damage, apoptosis, and generated ROS. Scavenging of vanadate-induced H(2)O(2) by N-acetyl-l-cysteine (a general antioxidant) or catalase (a specific H(2)O(2) inhibitor), or the chelation of vanadate by deferoxamine, resulted in inhibition of p53 activation and cell mitochondrial damage. In contract, an increase in H(2)O(2) generation in response to superoxide dismutase or NADPH enhanced these effects caused by vanadate. Furthermore, vanadate-induced apoptosis occurred in cells expressing wild-type p53 (p53+/+) but was very weak in p53-deficient (p53-/-) cells. These results demonstrate that vanadate induces p53 activation mainly through H(2)O(2) generation, and this activation is required for vanadate-induced apoptosis.

Acetylcysteine↗

Significance of organochlorine and heavy metal residues in wintering shorebirds at Corpus Christi, Texas, 1976-77.

Organochlorine and heavy metal residues were determined in 103 shorebirds of seven species collected at Corpus Christi, Texas, during the winter of 1976-77 to evaluate their potential effects on population survival, DDE and polychlorinated biphenyls (PCBs) were detected in most samples. Chlordane isomers, dieldrin, toxaphene, and heptachlor epoxide also occurred, but less frequently. In general, organochlorine residues were low in skinned carcasses. Geometric means on a wet weight basis ranged from 0.25 ppm to 4.76 ppm for DDE and from 0.67 ppm to 6.64 ppm for PCBs; residues of the other compounds averaged less than 1 ppm in all instances. Mercury, lead, arsenic and vanadium occurred in all shorebird livers, and selenium and cadmium were detected in all kidneys. Residues of these metals, except selenium, were low in most tissue samples. Selenium averages varied from 1.77 ppm to 5.62 ppm (wet weight) in kidneys; residues in this range may be sufficient to inhibit reproduction or to induce other forms of toxicity, especially at the higher levels.

Animals↗

Modulatory effects of peroxovanadates on insulin receptor binding.

The insulin-mimetic effects exhibited by vanadate, hydrogen peroxide, and some peroxovanadates have recently been shown to occur, at least in part, through an activation of the insulin receptor tyrosine kinase activity. In this study, we examine the effects of these compounds on insulin receptor binding using receptor preparations from human placental membranes. Among the 16 vanadium(V)-peroxo complexes studied, the [VO(O2)2(bipy)]- ion, where bipy = 2,2'-bipyridine, was found to increase insulin receptor binding by 24%, whereas the [VO(O2)2(en)]- ion, where en = ethylenediamine, was found to reduce insulin receptor binding by about the same amount under steady-state conditions. Scatchard analysis of the binding data indicates that the observed effect of the [VO(O2)2(bipy)]- ion on insulin receptor binding is exerted mainly at the high-capacity low-affinity sites. Furthermore, this modulatory effect is reversible and requires a continuous presence of the compound. By perturbing the membrane environment of the insulin receptor, we have shown that an intact membrane structure is essential for an observable effect. The observed modulation of insulin receptor binding by peroxovanadates is interpreted in terms of a ternary complex model in which the peroxovanadate acts as an allosteric effector modulating the binding equilibrium between insulin and its receptor.

Humans↗

Metals and metal compounds in cancer treatment.

Metals and metal compounds have been used in medicine for several thousands of years. In this review we summarized the anti-cancer activities of the ten most active metals: arsenic, antimony, bismuth, gold, vanadium, iron, rhodium, titanium, gallium and platinum. The first reviewed metal, arsenic, presents the anomaly of displaying anti-cancer and oncogenic properties simultaneously. Some antimony derivatives, such as Sb2O3, salt (tartrate) and organic compounds, show interesting results. Bismuth directly affects Helicobacter pylori and gastric lymphoma; the effects of bismuth complexes of 6-mercaptopurine are promising. Gold(I) and (III) compounds show anti-tumour activities, although toxicity remains high. Research into the potential use of gold derivatives is still ongoing. Several derivatives of vanadium show anti-proliferative activity, but their toxicity must be overcome. Several pieces of evidence indicate that iron deprivation could be an excellent therapeutic approach; furthermore, it is synergistic with classic anti-cancer drugs. Rhodium belongs to the same group as platinum and it also presents interesting activity, but with the same nephrotoxicity. Several rhodium compounds have entered phase I clinical trials. In contrast to the platinum complexes, titanium derivatives showed no evidence of nephrotoxicity or myelotoxicity; titanocene dichloride is undergoing clinical trial. The anti-proliferative effect of gallium could be related to its competition with the iron atom; in addition a derivative appears to reverse the multidrug resistance. The last metal reviewed, platinum, has given some of the very best anti-cancer drugs. Four derivatives are used today in the clinic; their mechanism of action and of resistance are described.

Animals↗

X-ray structure, solution properties, and biological activity profile of vanadocene(IV) acetylacetonate complex,.

The structure of [V(eta5-C5H5)2(CH3C(O)CHC(O)CH3)](O3SCF3) (1) (=[VCp2(acac)](O3SCF3)), a dual-function anti-cancer agent with anti-angiogenic and anti-mitotic properties, was determined by single-crystal X-ray diffraction. The geometry is well described as a pseudo-tetrahedral like structure with the centroids of the cyclopentadienyl rings and the two oxygen atoms of the acetylacetonate ring in the ancillary positions of the central vanadium (IV) atom. The bisector of the V(acac) fragment deviates from the C2 axis of the ligand framework by only 4 degrees, compared to a deviation of 7 degrees for the V(acac) fragment in the tetramethylethano-bridged vanadocene acetyl acetonate complex. Crystal data for 1: space group, P2(1)/c; a=7.5544(9) A, b=14.936(2) A, c=16.193(2) A, beta=102.901(2) degrees, V= 1781.0(4) A3; Z=4; R=0.0506 for 2310 reflections with I> 2sigma(I). This report also details the electron paramagnetic resonance, UV/Vis spectroscopy, electrochemical properties and the biological activity profile of this potent anti-cancer agent.

Angiogenesis Inhibitors↗

Bis(allixinato)oxovanadium(IV) complex is a potent antidiabetic agent: studies on structure-activity relationship for a series of hydroxypyrone-vanadium complexes.

There is an urgent medical need for orally effective drugs to replace insulin injections for the treatment of diabetes mellitus. Vanadium complexes with insulin-mimetic activities have recently been proposed as candidates as new antidiabetic drugs. Following in vitro and in vivo studies on a group of bis(3-hydroxy-4-pyronato)oxovanadium(IV) (1) complexes with VO(O4) coordination mode, bis(allixinato)oxovanadium(IV) (3) which contains allixin, a garlic component, was found to be the most potent antidiabetic agent among them. Complex 3 with a high in vitro insulin-mimetic activity in terms of both free fatty acid (FFA)-release inhibitory and glucose-uptake enhancing activities in isolated rat adipocytes exhibited a high hypoglycemic effect in type 1 diabetic model mice by both intraperitoneal injections and oral administrations. Complex 3 is thus proposed to be one of the most effective candidates for antidiabetic therapy.

Adipocytes↗

V2Al5Ge5: first ternary intermetallic in the V-Al-Ge system accessible in liquid aluminium.

The intermetallic compound V2Al5Ge5 grown from Al flux is reported. V2Al5Ge5: orthorhombic, Cmcm, a = 5.4072(10), b = 12.978(2), and c = 11.362(2) A, the structure features distorted pentagonal prismatic columns defined by Al and Ge atoms. Vanadium atoms occupy the central axis of columns forming a chain with long-short alternation of V-V bonds. This compound is resistant to air oxidation up to 500 degrees C.

Journal Article↗

Crystal structure study of a beta'-copper vanadium bronze, Cu(x)V2O5 (x = 0.63), by X-ray and convergent beam electron diffraction.

The single-crystal structure of a beta'-copper vanadium bronze, Cu0.63V2O5, has been studied at room temperature and 9.6 K, and compared with that of the beta-sodium vanadium bronze, Na0.33V2O5, structure. No convincing evidence to oppose an assignment of centrosymmetric C2/m symmetry to the structure was identified using the X-ray data. A subsequent convergent beam electron diffraction (CBED) experiment was performed and confirmed the C2/m space group. The oxygen-vanadium atom framework of Cu0.63V2O5 is close to that of Na0.33V2O5. However, in the copper compound the Cu atoms are located in two positions: Cu1 in the 4(i) position with x=0.541, y=0 and z=0.345, and Cu2 in the 8(j) position with x=0.529, y=0.038 and z=0.357. The crystal structure changes little with temperature. Disorder of the Cu ion over two sites is seen at 9.6 K. This suggests that distribution of the Cu atoms over two sites is of a more static than dynamic nature.

Alloys↗

Modeling reactive metal oxides. Kinetics, thermodynamics, and mechanism of M(3) cap isomerization in polyoxometalates.

An investigation of M(3)O(13) unit ("M(3) cap") isomerization in the classical polytungstodiphosphates alpha- and beta-P(2)W(18)O(62)(6)(-) has been undertaken because cap isomerism is an important and structurally well-studied phenomenon in many polyoxometalate families. The relative thermodynamic stabilities of the alpha (more stable) versus beta isomers were established both in the solid state by differential scanning calorimetry (4.36 +/- 0.64 kcal/mol) and in solution by (31)P NMR (3.80 +/- 0.57 kcal/mol). The isomerization of beta-P(2)W(18)O(62)(6)(-) to alpha-P(2)W(18)O(62)(6)(-), followed by (31)P NMR, has a bimolecular rate constant k(2) of 9.3 x 10(-)(1) M(-)(1) s(-)(1) at 343 K in pH 4.24 acetate buffer. Several lines of evidence establish the validity of suggestions in the literature that isomerization goes through a lacunary (defect) intermediate. First, the rate is proportional to [OH(-)]. Second, isomerization increases at higher ionic strengths, and a Debye-Hückel plot is consistent with a rate-limiting reaction between beta-P(2)W(18)O(62)(6)(-) and OH(-) (two species with a charge product of 6). Third, alkali-metal cations stabilize the bimolecular transition state (K(+) > Na(+) > Li(+)), consistent with recent ion-pairing studies in polyoxometalate systems. Fourth, the monovanadium-substituted products alpha(1)- and alpha(2)-P(2)VW(17)O(62)(7)(-) ((51)V NMR delta -554 ppm) form during isomerization in the presence of VO(2+). The known lacunary compounds (alpha(1)- and alpha(2)-P(2)W(17)O(61)(10)(-)) also react rapidly with the same vanadium precursor. Fifth, solvent studies establish that isomerization does not occur when OH(-) is absent. A mechanism is proposed involving attack of OH(-) on beta-P(2)W(18)O(62)(6)(-), loss of monomeric W(VI) from the M(3) (M(3)O(13)) terminal cap, isomerization of the resulting lacunary compound to alpha-P(2)W(17)O(61)(10)(-), and finally reaction of this species with monomeric W(VI) to form the thermodynamic and observed product, alpha-P(2)W(18)O(62)(6)(-).

Journal Article↗

Complexes of metals other than platinum as antitumour agents.

The earliest reports on the therapeutic use of metals or metal-containing compounds in cancer and leukemia date from the sixteenth and nineteenth centuries. They were forgotten until the 1960s, when the anti-tumour activity of the inorganic complex cis-diammine-dichloroplatinum(II) (cisplatin) was discovered. This led to the development of other types of non-organic cytostatic drugs. Cisplatin has developed into one of the most frequently used and most effective cytostatic drugs for the treatment of solid carcinomas. Numerous other metal compounds containing platinum, other platinum metals, and even non-platinum metals were then shown to be effective against tumours in man and experimental tumours in animals. These compounds comprise main-group metallic compounds of gallium, germanium, tin, and bismuth, early-transition metal complexes of titanium, vanadium, niobium, molybdenum, and rhenium, and late-transition metal complexes of ruthenium, rhodium, iridium, platinum, copper, and gold. Several platnium complexes and four non-platnium-metal antitumour agents have so far entered early clinical trials. Gallium trinitrate and spirogermanium have already passed phase II clinical studies and have shown limited cytostatic activity against certain human carcinomas and lymphomas. The two early-transition metal complexes budotitane and titanocene dichloride have just reached the end of phase I clinical trials and have been found to have an unusual pattern of organ toxicity in man. Titanocene dichloride will soon enter phase II clinical studies.

Animals↗

Vanadate inhibition of brain (Ca + Mg)-ATPase.

Vanadate was a potent inhibitor of the membrane-bound (Ca + Mg)-ATPase from rat brain, the concentration required for 50% inhibition under conditions optimal for enzymatic activity being 3 mu M. Vanadate inhibition increased with the MgCl2 concentration, half-maximal inhibition occurring at 2 mM MgCl2, near the MgCl2 concentration required for half-maximal activation of the ATPase activity. MnCl2 could substitute for MgCl2, and at concentrations of 1 mM (Ca + Mn)-ATPase activity was greater than (Ca + Mg)-ATPase activity, although sensitivity to vanadate was less. Vanadate inhibition increased also with the KCl concentration, half-maximal inhibition occurring at 8 mM, again near the concentration required for half-maximal activation of ATPase activity. By contrast, NaCl stimulated (Ca + Mg)-ATPase activity without potentiating vanadate inhibition. These effects of cations on ATPase activity and vanadate inhibition resemble properties of certain transport ATPases and thus suggest mechanistic and functional similarities.

Animals↗

Ferrous iron uptake by Bifidobacterium bifidum var. pennsylvanicus: the effect of metals and metabolic inhibitors.

Ferrous iron uptake studies in Bifidobacterium bifidum var. pennsylvanicus were carried out in a well-defined salt solution termed "modified Hanks solution" at both high iron concentrations (LAFIUS conditions) and low concentrations (HAFIUS conditions). Various divalent metals, Mn2+, Zn2+, Ni2+ and Cu2+, inhibited iron uptake under HAFIUS conditions in a non-competitive manner, and in a pseudo-competitive manner under LAFIUS conditions. Cr2+ had no effect. Co2+ inhibited iron uptake competitively under HAFIUS conditions. Metabolic affectors that inhibited iron uptake both under HAFIUS and LAFIUS conditions were: tetraphenylphosphonium chloride, diethylstilbesterol, vanadate, carbonylcyanide-m-chlorophenyl-hydrazone, and a mixture of valinomycin and nigericin. Substances that stimulated iron uptake were KCl, valinomycin, and nigericin. Iron uptake under LAFIUS conditions in piperazine-buffered modified Hanks solution was higher than that in the acetate-buffered solution, and acetate inhibited iron uptake in the piperazine buffer. HAFIUS showed no difference. It is concluded that iron uptake in bifidobacteria is driven by an ATPase-dependent proton-motive force and that both the pH gradient and membrane potential are involved in this process. Mn2+, Zn2+, Ni2+, and Cu2+ may be transported via LAFIUS, but not HAFIUS. HAFIUS may transport only Co2+ in addition to Fe2+.

Bifidobacterium↗

1,2,4,5-Tetra([5]trovacenyl)benzene: an organometallic tetraradical displaying pronounced electro- and magnetocommunication.

The organometallic tetraradical 1,2,4,5-[(eta)7-C7H7)V(all eta]5-C5H4)]4C6H2 has been prepared and structurally characterized. The isotropic EPR spectrum displays 29 a(51V) hyperfine lines, the intensity distribution slightly deviating from binomial. Exchange coupling therefore approaches the strong exchange limit, J(ortho) not equal to J(meta) not equal to J(para) greater or approximately 50 a(51V) with a(51V)= 0.0067 cm(-1). According to magnetic susceptometry, the interaction is antiferromagnetic. While redox splittings deltaE(1/2) are resolved for the four reduction steps this is not the case for oxidation.

Electrochemistry↗

Metals and metal compounds in carcinogenesis.

Several metals and metal containing compounds are potent mutagens and carcinogens. The most often blamed are chromium, arsenic, nickel, vanadium, iron, copper and manganese. Although each of them has its own mechanism of action, it is believed that most of their mechanisms of action involve reactive oxygen species (ROS). Furthermore, nickel modulates gene expression by induction of DNA methylation and/or suppression of histone acetylation. Arsenic activity on cell metabolism is multiple; it seems that cell transformation is induced by long-term exposure to a low level of arsenic. The paradox of arsenic is that it has also a valuable therapeutic efficacy in cancer treatment. Manganese is known to cause DNA damage, although it does not represent a significant carcinogenic risk. Magnesium deficiency and iron excess are not exactly carcinogenetic, but certain concentrations of these metal ions are needed to prevent cancer.

Carcinogens↗