Correlation between structure of polyoxotungstates and their inhibitory activity on polymerases

The 21-tungsto-9-antimonate (TA, HPA 23), a polyoxotungstate, has shown a significant antiviral activity in vivo and in vitro. It inhibits viral and bacterial DNA polymerases. In this paper, several compounds of two polyoxotungstic families, tungstoantimonates and tungstoarsenates, have been used to specify the mechanism of polymerase inhibition. It has been demonstrated that the inhibitory activity of polyoxotungstates is not related to the occupation of their coordinative sites by cations, nor to the nature of these bound cations. Kinetic studies and binding assays have shown that polyoxotungstates bind to the polymerases in competition with the nucleic acid template. This result seems to be related to their polyanionic nature. Furthermore, the size and charge of these compounds may play a prominent part in their affinity for the polymerases.     

Hydrothermal syntheses and characterizations of 0D to 3D polyoxotungstates linked by copper ions

A new family of hybrid organic-inorganic materials built from polyoxotungstates and Cu(II) ions as linkers has been synthesized by hydrothermal reactions from a mixture of sodium tungstate, copper chloride and ethylenediamine. The initial pH and the presence or absence of heteroelement (P, Si) control the nature of the polyoxotungstate clusters and their connectivity via the copper ions, and hence the dimensionality of the framework. In the absence of heteroelement, three compounds have been isolated: at low pH (5) the molecular compound [Cu(en)₂(H₂O)]₂[{Cu(en)₂}H₂W₁₂O₄₀] · 10H₂O (1) is formed, at neutral pH the 3D material [{Cu(en)₂}₃{Cu(en)}₂H₂W₁₂O₄₂] · 27H₂O (2) and at high pH (11) the 2D compound [Cu(en)₂(H₂O)₂][Cu(en)₂][{Cu(en)₂}₃H₂W₁₂O₄₂] · 15H₂O (3). In the whole range of pH (5-11.5) a single phase has been obtained with silicium as heteroelement, namely the 2D material [Cu(en)₂(H₂O)][{Cu(en)₂}₂SiW₁₁CuO₃₉] · 7H₂O (4) with chains of Keggin polyoxotungstates linked by {Cu(en)₂}²⁺ groups. Finally, a phosphotungstate with a chain-like structure has been characterized, [{Cu(en)₂}₃PW₁₁CuClO₃₉] · 6H₂O (5), at low pH (5) which differs from the phase obtained at higher pH.     

Antibacterial activity of highly negative charged polyoxotungstates, K27[KAs4W40O140] and K18[KSb9W21O86], and Keggin-structural polyoxotungstates against Helicobacter pylori

The antibacterial activity of polyoxometalates (PMs) against Helicobacter pylori was investigated based on determinations of minimum inhibitory concentration (MIC) and fractional inhibitory concentration (FIC), time-killing of the bacteria, bacterial morphology and PM-uptake into the bacteria cell. The result of MIC values revealed that, of 13 PMs used in this study, highly negative-charged polyoxotungstates, such as K27[KAs4W40O140] and K18[KSb9W21O86], and Keggin-structural polyoxotungstates exhibited a potent antibacterial activity with the MIC values of less than 256 microg/ml. The former was the most active, and superior to metronidazole (MTZ) against MTZ-susceptible and resistant strains and also to clarithromycin (CLR) against CLR-resistant strains. In contrast, most of polyoxomolybdates showed little antibacterial activity with the MIC values of more than 256 microg/ml. The result of FIC index values indicated that the antibacterial polyoxotungstates had partially synergistic effect in combination with MTZ and CLR but indifferent effect in combination with amoxicillin (AMX). From the results of the time-killing and scanning electron microscope images, K27[KAs4W40O140] and K18[KSb9W21O86] proved the concentration-dependent bactericidal activity with the morphological change from bacillary form to coccoid form, while Keggin-structural K5[SiV(V)W11O40] showed the bacteriostatic activity with small change of morphology to coccoid form. The fluorescent X-ray analysis demonstrated that these polyoxotungstates were taken into the bacteria cell. It is pointed out that the Keggin-structure and/or high negativity polyoxotungstates are an important factor for the antibacterial activity against H. pylori.     

Two novel sandwiched-type polyoxotungstates containing Zn6 transition-metal cluster: Syntheses, structures and luminescent property

Two novel Zn6 sandwiched polyoxometalates, [Zn(phen)₂]₂[Zn₆(phen)₂(AsW₉O₃₃)₂] (1) and K₁₁H₂Zn[(ZnCl)₆(AsW₉O₃₃)₂]Cl · 27H₂O (2), have been synthesized and characterized by X-ray single-crystal analysis, IR, and fluorescence spectrum. The polyoxoanions in both compounds can be characterized as two {As^IIIW₉O₃₃}⁹⁻ moieties linked through Zn6 transition-metal cluster to form the sandwich-type polyoxotungstates. In compound 1, six Zn atoms in the equatorial part of the polyoxoanions have two different coordination environments: four Zn sites exhibit distorted octahedral geometry, and the other two Zn atoms show square pyramidal geometry. In the polyoxoanion of compound 2, all Zn atoms are square pyramidal geometry, and held together to form a hexagonal metallocycle by edge-sharing oxygen atoms. In this Zn6 cluster, the shortest distance of neighboring Zn?Zn is 3.147(1) Å. In addition, compound 2 exhibits purple photoluminescence at room temperature.     

A new host 3D copper(I/II)-pyrazinecarboxylate framework intercalated with Keggin polyoxotungstates

Two new Cu(I/II) coordination polymers based on α-Keggin polyoxotungstates, [Cu₆(2-pzc)₅(H₂O)₂(XW₁₂O₄₀)]·H₂O (X = Si, 1; Ge, 2) (2-pzc = 2-pyrazinecarboxylate), have been synthesized hydrothermally and characterized structurally. Single crystal structure analysis reveals that they are isomorphic, and exhibit a novel 3D framework constructed from Cu(I/II) ions and 2-pzc ligands, in which there exist nano-sized channels viewed along the a axis and the c axis. The [XW₁₂O₄₀]⁴⁻ anions are filled in the channels, acting as not only a template, but also a hexa-dentate ligand. Additionally, the photocatalytic hydrogen production of 1 and 2 was investigated. It is found that 1 and 2, as heterogeneous catalysts, exhibit the photocatalytic activity in the UV region.     

Synthesis and structural investigation of sandwich polyoxotungstates containing cerium (III/IV) and mono-lacunary Keggin tungstophosphate units

The two isostructural anions, [Ce^III(α-PW₁₁O₃₉)₂]¹¹⁻ and [Ce^IV(α-PW₁₁O₃₉)₂]¹⁰⁻, both composed of Ce^III/IV sandwiched by two mono-lacunary Keggin units [α-PW₁₁O₃₉]⁷⁻, were isolated as dimethylammonium salts and structurally characterized by single-crystal X-ray diffraction analysis. The structures of the [Ce^III/IV(α-PW₁₁O₃₉)₂]^11−/10− anions exhibit two enantiomers d- and l-forms due to C₂ (2) symmetry from the square-antiprismatic coordination of the central Ce^III/IVO₈ polyhedron. The Ce^III compound crystallizes in achiral space group P2₁/n, while the Ce^IV analog in chiral space group P2₁ shows spontaneous resolution without any chiral auxiliaries. The correlation between the ionic radius of the central metal (M) and twist angle of the two mono-lacunary units was studied for a series of [M(α-PW₁₁O₃₉)₂]ⁿ⁻ (M = Ce^III/IV, Eu^III, Zr^IV, Hf^IV) anions and explained in terms of steric repulsion between the O atoms in the mono-lacunary units.     

Insulin mimetic effect of a tungstate cluster. Effect of oral administration of homo-polyoxotungstates and vanadium-substituted polyoxotungstates on blood glucose level of STZ mice

Aqueous vanadate and aqueous tungstate have been known to mimic all or most of the actions of insulin in intact cell systems with respect to normalization of the blood glucose level. By carrying out oral administration in vivo experiments on the blood glucose level of streptozotocin (STZ)-induced diabetes (STZ mice), the insulin-mimetic (IM) effects of metal-oxide clusters of all-inorganic composition were examined using many types of polyoxometalates (POM) with and without vanadium substitution. Several homo-POM and vanadium-substituted POM showed hypoglycemic effects. The observed hypoglycemic effects indicated that POM with the Dawson structure [[alpha-P(2)W(18)O(62)](6-) (W-2), [alpha-P(2)W(17)V(V)O(62)](7-) (V-19) and [alpha-1,2,3-P(2)W(15)V(V)(3)O(62)](9-) (V-04)] are more effective than those with the Keggin structure [[alpha-PW(12)O(40)](3-) (W-1), [alpha-PW(11)V(V)O(40)](4-) (V-01), [alpha-1,2-PW(10)V(V)(2)O(40)](5-) (V-02), [alpha-1,2,3-PW(9)V(V)(3)O(40)](6-) (V-03) and [alpha-1,4,9-PW(9)V(V)(3)O(40)](6-) (V-13)]. The vanadate cluster [V(10)O(28)](6-) (V-15) also showed a hypoglycemic effect. (31)P and (51)V NMR measurements showed that the Dawson POM (W-2, V-04 and V-19) are stable in aqueous solution under the conditions used. The effect of all POM on the body weight of STZ mice was also examined. The decrease in body weight after administration of W-2 was much less than for V-19, V-04 and V-15. This suggests that not only monomeric tungstate and vanadate, but also the structure factors of tungstate and vanadate clusters, can play a significant role in their biological action.     

Rearrangement of unsaturated 2,4-O-benzylidenehexitol derivatives into C-glycosylbenzene derivatives.

Acetolysis of (Z)-1,3-di-O-acetyl-2,4-O-benzylidene-6-C-(2,4-dichlorophenyl)-D-xylo-he x- 5-enitol (3) afforded (E)-1,2,3,4-tetra-O-acetyl-6-C-(2,4-dichlorophenyl)-D-xylo-hex-5-enit ol and 2-C-[(R)-acetoxy(2,4-dichlorophenyl)methyl]-3,4,6-tri-O-acetyl-2-deoxy- beta-L-galacto- and -beta-L-gulo-hexopyranosylbenzene. The mechanism of this new rearrangement was studied by exchanging the substituents at C-1 and C-3 in 3 and those of the aromatic ring attached to C-6.     

Steroid derivatives

Mycobacterium flavum was used to effect the transformation of 16β-methyl-16,17-oxido-7β,11α-dihydroxypregn-4-ene-3,20-dione (I) and the final products were isolated and identified as 16β-methyl-16,17-oxido-7β,11α-dihydroxypregna-1,4-diene-3,20-dione (II) and 16β-methyl-16,17-oxido-11α-hydroxypregna-1,4,6-triene-3,20-dione (IV), and the intermediate product as 16β-methyl-16,17-oxido-11α-hydroxypregna-4,6-diene-3,20-dione (III).     

Steroid derivatives

It was found in a study of the hydroxylating capacity of one of theFungi imperfecti, the genusBeauveria, some of the species of which are able to introduce the oxygen function into position 11α of various steroid compounds, that the enzyme activity ofBeauveria globulifera gives rise both to the corresponding 11α-hydroxy-derivative and to the 5β-saturated 11α-hydroxy-compound or a 5β-saturated 7β,11α-dihydroxy-compound. The isolation and the identification of the products of biotransformation of some steroids of the pregnane and androstane series byBeauveria globulifera is described.     

Steroid derivatives

The microorganismsBacillus sphaericus, Septomyxa affinis andProactinomyces globerulus dehydrogenate 17β-hydroxy-17α-methyl-5α-androstan-3-one to corresponding 1-, or 1,4-unsaturated derivatives. However, the biotransformation of the cited compound byArthrobacter simplex andMycobacterium flavum simultaneously introduced one atom of oxygen into the 17a-position and resulted in the formation of 17β hydroxy-17α-methyl-17a-oxa-D-homo-5α-1-androsten-3-one.     

Steroid derivatives

Microbial transformation of some steroid 19-hydroxy compounds and 1(10),5-dienes, substituted by a hydroxyl group in position 3, by the action ofProactinomyces globerulus, yielded substances with aromatic A ring. Substrates with 17-keto group underwent simultaneously a partial reduction resulting in the formation of 17β-hydroxyl.     

Steroid derivatives

Biotransformation of dehydroepiandrosterone (I) and methylandrostenediol (VI) by means of the microorganismAbsidia orchidis yielded a mixture of epimeric 7-hydroxyderivatives II or VII. Microbial oxidation of these mixtures byFlavobacterium peregrinum afforded epimeric 7-hydroxyderivatives of 4-androsten-3,17-dione III and IV, or of methyltestosterone VIII and IX. The structure of these compounds was confirmed by partial synthesis.     

Steroid derivatives

The dependence of the course of hydroxylation of steroid compounds substituted differently in positions 16 and 17 was studied, using several economically important 11α-hydroxylating microorganisms. All the steroid substrates used yielded the 11α-hydroxy-derivative as the main product, with the exception of 16β-methyl-16α, 17-oxidoprogesterone, during the biotransformation of which the formation of the 11α-hydroxy-derivative was accompanied by appreciable amount of its 7β,11α-dihydroxyderivative. In the transformation achieved byBeauveria bassiana, the last-named dihydroxy-compound was formed as the main product, whereas the biotransformation carried out with the aid ofBeauveria globulifera yielded the 5-saturated analogue of 7β,11α-dihydroxy-methylepoxyprogesterone as the main product.     

Steroid derivatives

Hydroxylation of l7α-acetoxy-6-chloro-16-methylene-4,6-pregnadiene-3,20-dione (Chlorosuperlutin, I) byCunninghamella blakesleeana yielded a 15β-hydroxyderivative II. Analogous transformation of 17α-acetoxy-16-methylene-4,6-pregnadiene-3,20-dione (Superlutin, IV) included a hydroxylation in position 15β and probably also in 11β with a concomitant reduction of the 6,7-double bond.