Synthesis and reactivity studies of model complexes for molybdopterin-dependent enzymes

The molybdenum cofactor (Moco)-containing enzymes are divided into three classes that are named after prototypical members of each family, viz. sulfite oxidase, DMSO reductase and xanthine oxidase. Functional or structural models have been prepared for these three prototypical enzymes: (i) The complex [MoO2(mnt)2]2- (mnt2- = 1,2-dicyanoethylenedithiolate) has been found to be able to oxidize hydrogen sulfite to HSO4- and is thus a functional model of sulfite oxidase. Kinetic and computational studies indicate that the reaction proceeds via attack of the substrate at one of the oxo ligands of the complex, rather than at the metal. (ii) The coordination geometries of the mono-oxo [Mo(VI)(O-Ser)(S2)2] entity (S2 = dithiolene moiety of molybdopterin) found in the crystal structure of R. sphaeroides DMSO reductase and the corresponding des-oxo Mo(IV) unit have been reproduced in the complexes [M(VI)O(OSiR3)(bdt)2] and [M(VI)O(OSiR3)(bdt)2] (M = Mo,W; bdt = benzene dithiolate). (iii) A facile route has been developed for the preparation of complexes containing a cis-Mo(VI)OS molybdenum oxo, sulfido moiety similar to that detected in the oxidized form of xanthine oxidase.     

Cytotoxicity studies of chromium(III) complexes on human dermal fibroblasts

The cytotoxicity of certain Cr(III) complexes, such as [Cr(salen)(H(2)O)(2)](+), [Cr(edta)(H(2)O)](-), [Cr(en)(3)](3+), [Cr(ox)(3)](3-), [Cr(pic)(3)], and CrCl(3), which differ in ionic character and ligand environment in human dermal skin fibroblasts, has been studied. After 72 h of exposure to 100 microM doses of chromium(III) complexes, the order in which the complexes had an inhibitory effect on cell viability was [Cr(en)(3)](3+) > [Cr(salen)(H(2)O)(2)](+) > [Cr(ox)(3)](3-) > [Cr(edta)(H(2)O)](-) > [Cr(pic)(3)] > CrCl(3). Based on viability studies it was confirmed that [Cr(en)(3)](3+), a triply charged cation, inhibits cell proliferation, and therefore, it was chosen to carry out further investigations. [Cr(en)(3)](3+), at a dose of 50 microM, was found to bring about surface morphological changes, evidenced by cellular blebbing and spike formation accompanied by nuclear damage. TEM analysis revealed substantial intracellular damage to fibroblasts in terms of the formation of apoptotic bodies and chromatin condensation, thus reflecting cell death. FACS analysis further revealed DNA damage by formation of a sub-G(1) peak with 84.2% DNA as aneuploid DNA and arrest of the G(2) / M phase of the cell cycle. Cellular DNA damage was confirmed by agarose gel electrophoresis with the characteristic appearance of a DNA streak in DNA isolated from [Cr(en)(3)](3+)-treated fibroblasts. The proposed mechanism suggests the plausible role of Cr(V), formed as a result of oxidation of Cr(III) by cellular oxidative enzymes, in the cytotoxic response. Consequently, any Cr(III) complex that is absorbed by cells and can be oxidized to Cr(V) must be considered a potential carcinogen. This has potential implications for the increased use of Cr(III) complexes as dietary supplements and highlights the need to consider the cytotoxicity and genotoxicity of a variety of Cr(III) complexes and to understand the potential hazards of Cr(III) complexes encountered in research laboratories.     

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.     

The uptake and fate of vanadyl ion in ascidian blood cells and a detailed hypothesis for the mechanism and location of biological vanadium reduction. A visible and X-ray absorption spectroscopic study

Vanadium K-edge X-ray absorption spectroscopy (XAS) has been used to track the uptake and fate of VO(2+) ion in blood cells from Ascidia ceratodes, following exposure to dithiothreitol (DTT) or to DTT plus VO(2+). The full range of endogenous vanadium was queried by fitting the XAS of blood cells with the XAS spectra of model vanadium complexes. In cells exposed only to DTT, approximately 0.4% of a new V(III) species was found in a site similar to Na[V(edta)(H(2)O)]. With exposure to DTT and VO(2+), average intracellular [VO(aq)](2+) increased from 3% to 5%, and 6% of a new complexed form of vanadyl ion appeared evidencing a ligand array similar to [VO(edta)](2-). At the same time, the relative ratio of blood cell [V(H(2)O)(6)](3+) increased at the expense of [V(H(2)O)(5)(SO(4))](+) in a manner consistent with a significant increase in endogenous acidity. In new UV/Visible experiments, VO(2+) could be reduced to 7-coordinate [V(nta)(H(2)O)(3)] or [V(nta)(ida)](2-) with cysteine methyl ester in pH 6.5 solution. Ascorbate reduced [VO(edta)](2-) to 7-coordinate [V(edta)(H(2)O)](-), while [VO(trdta)](2-) was unreactive. These results corroborate the finding that the reductive EMF of VO(2+) is increased by the availability of a 7-coordinate V(III) product. Finally, a new and complete hypothesis is proposed for an ascidian vanadate reductase. The structure of the enzyme active site, the vanadate-vanadyl-vanadic reduction mechanism, the cellular locale, and elements of the regulatory machinery governing the biological reduction of vanadate and vanadyl ion by ascidians are all predicted. Together these constitute the new field of vanadium redox enzymology.     

C4' sugar oxidation of deoxyribonucleotide triphosphates by chromium(V) complexes

The Cr(V) complexes, bis(2-ethyl-2-hydroxybutyrato)oxochromate(V) ([OCr(V)(ehba)(2)](-)) and (2,2-bis(hydroxymethyl)-2-(bis(2-hydroxyethyl)amino)ethanolato)oxochromate(V) ([OCr(V)(BT)](2-)), were reacted with a series of deoxyribonucleotide triphosphates. Oxidation of deoxyribose at C4' was observed by measuring the amount of thiobarbituric acid reactive species (TBARS) produced in these reactions. For both compounds, the TBARS obtained with purine nucleotides was between 2.25 and 3.5 times greater than what was observed with pyrimidine nucleotide. This result suggests that the identity of the nucleic acid base can influence the hydrogen atom abstraction at C4'. Overall, the amount of product obtained with [OCr(V)(BT)](2-) was significantly less than what was observed with [OCr(V)(ehba)(2)](-), indicating that these two Cr(V) model complexes may oxidize DNA differently.     

Intermediates formed by laser flash photolysis of [PtCl(6)](2-) in aqueous solutions.

The stationary photolysis of [PtCl(6)](2-) in aqueous solutions (10(-5)-10(-4) M) at the region of 313 nm leads to its photoaquation with a quantum yield of 0.19. Laser flash photolysis experiments (308 nm) provided evidence of the formation of Pt(iii) intermediates, namely [PtCl(4)(OH)(H(2)O)](2-) and [PtCl(4)](-), and Cl(2) (-) radical anions. The Pt(iii) complexes formed as a result of an intrasphere electron transfer from Cl(-) ligands to the excited Pt(iv) ion. However, the main ( approximately 90%) photolysis channel was not accompanied by the transfer of Cl atoms to the solvent bulk. The photoaquation of [PtCl(6)](2-) results from the back electron transfer in the secondary geminate pair, [PtCl(5)(H(2)O)](2-)-Cl. The relative yield of Pt(iii) intermediates, recorded after the completion of all processes in the geminate pair, was less than 10% of the number of disappearing initial [PtCl(6)](2-) complexes.     

Vanadium(V) complexes with salicylaldehyde semicarbazone derivatives bearing in vitro anti-tumor activity toward kidney tumor cells (TK-10): crystal structure of [VVO2(5-bromosalicylaldehyde semicarbazone)

As a contribution to the development of novel vanadium complexes with pharmacologically interesting moieties, new dioxovanadium(V) semicarbazone complexes with the formula cis-VO(2)L, where L=5-bromosalicylaldehyde semicarbazone and 2-hydroxynaphtalen-1-carboxaldehyde semicarbazone have been synthesized and characterized by (1)H and (13)C NMR, Raman and FTIR spectroscopies. Results were compared with those previously reported for other three analogous complexes of this series. The five complexes were tested in three different human tumor cell lines for bioactivity as potential anti-tumor agents, showing selective cytotoxicity on TK-10 cell line. Results showed that structural modifications on the semicarbazone moiety could have a significant effect on the anti-tumor activity of the vanadium complexes. In addition, the electrochemical behavior of all the complexes was studied. No apparent correlation could be demonstrated between reduction potentials of the complexes and their anti-tumor activities. The molecular structure of the novel [V(V)O(2)(5-bromosalicylaldehyde semicarbazone)] complex was solved by X-ray diffraction methods. The vanadium atom shows a distorted square pyramidal coordination sphere. The (VO(2))(+) cation is coordinated to a nearly planar (L)(-) anion acting as a tridentate ligand through both oxygen and one nitrogen atoms.     

Interactions of glucose oxidase with various metal polypyridine complexes as mediators of glucose oxidation

The interaction between glucose oxidase (GOx) and a typical metal complex, which is chemically stable in both oxidized and reduced forms, has been investigated by a voltammetric method. The evaluation of an electron-transfer mediator useful for glucose oxidation is discussed from thermodynamic and kinetic points of view, i.e. the redox potentials of various metal complexes and the second-order rate constants for the electron transfer between GOx in reduced form and the metal complexes in oxidized form. No mediation of glucose oxidation by [Co(bpy)(3)](2+) (bpy=2,2'-bipyridine) or [Cu(bpy)(2)](2+) occurred, in spite of their appropriate redox potentials. This was attributed mainly to the lower electron-self-exchange rates of the mediator and the reaction with GOx. All three types of osmium(II) complexes, [Os(PP) (n)](2+) ( n=2 or 3; PP=polypyridine), [OsL(2)(PP)(2)](2+) (L=imidazole and its derivatives), and [OsClL(bpy)(2)](+), acted as excellent electron-transfer mediators for the glucose oxidation. Mixed ligand complexes, [OsL(2)(PP)(2)](2+) and [OsClL(bpy)(2)](+), have been concluded to be more efficient electron-transfer mediators. The electron-transfer rates between the mediator and GOx have been found to be accelerated by intermolecular electrostatic interactions or hydrogen bonds.     

FeFe]-Hydrogenase active site models with relatively low reduction potentials: Diiron dithiolate complexes containing rigid bridges

Three diiron dithiolate complexes containing rigid and conjugated bridges, [mu-SC(6)H(4)-2-(CO)S-mu]Fe(2)(CO)(6) (1), [2-mu-SC(5)H(3)N-3-(CO)S-mu]Fe(2)(CO)(6) (2), and the PPh(3)-monosubstituted complex [mu-SC(6)H(4)-2-(CO)S-mu]Fe(2)(CO)(5)(PPh(3)) (1-P), were prepared as biomimetic models for the [FeFe]-hydrogenase active site. The structures of complexes 1 and 2 were determined by single crystal X-ray analysis, which shows that each complex features a rigid coplanar dithiolate bridge with a 2-3 degrees deviation from the bisect plane of the molecule. The influence of the rigid bridge on the reduction potentials of complexes 1, 2 and 1-P was investigated by electrochemistry. The cyclic voltammograms of complexes 1 and 2 display large positive shifts for the primary reduction potentials, that is, 380-480mV in comparison to that of the pdt-bridged (pdt=propane-1,3-dithiolato) complex (mu-pdt)Fe(2)(CO)(6) and 160-260mV to that of the bdt-bridged (bdt=benzene-1,2-dithiolato) analogue (mu-bdt)Fe(2)(CO)(6).     

Synthesis and characterization of binuclear molybdenum-polycarboxylate complexes with sulfur bridges

A group of four binuclear sulfur-bridged molybdenum-polycarboxylato complexes with homocitrate, citrate, cysteine, ethylenediaminetetraacetate ligands, respectively, have been synthesized and characterized. These complexes were prepared in order to study the interaction of Mo and homocitrate in the FeMo-co of nitrogenases. In the structures of K4(NH4)2[Mo2O2S2(C6H4O7)2].10H2O (2), (NH4)2[Mo2O2S2(C3H5SNO2)2].5H2O (3) and (NH4)2[Mo2O2S2(C10H12N2O8)].3.5H2O (4), molybdenum (V) atom adopts a distorted octahedral arrangement through a terminal oxygen atom, two bridging sulfur atoms and three atoms from the ligand (hydroxyl, alpha-, beta-carboxylates, sulfide or amine). The coordination mode of homocitrate ligand in K5(NH4)[Mo2O2S2(C7H5O7)2].3H2O.CH3OH (1) has been proposed in a tridentate fashion via its hydroxyl and a pair of carboxylate groups (alpha-, beta-carboxylates). The electrochemical properties of these complexes have been discussed.     

Reactivity of potential anti-diabetic molybdenum(VI) complexes in biological media: a XANES spectroscopic study

The application of Mo(VI) complexes as anti-diabetic agents is a subject of considerable recent interest. The stability and speciation of [Mo(VI)O(4)](2-) and three analogs of known anti-diabetic V(IV) complexes ([Mo(VI)O(2)L(2)]; where LH=2,4-pentanedione, l-cysteine ethyl ester or N,N-diethyldithiocarbamic acid) in natural and simulated biological fluids (including blood and its components, cell culture media, and artificial digestion systems) were studied using MoK-edge XANES (X-ray absorption near-edge structure) spectroscopy of freeze-dried samples at 20K. All of the studied [MoO(2)L(2)] complexes decomposed extensively under simulated gastric and intestinal digestion conditions (3 h at 310 K), as well as in blood plasma or in cell culture medium (24 h at 310 K). The reaction products of [MoO(4)](2-) and [MoO(2)L(2)] with biological fluids could be satisfactorily modelled (using multiple linear regression analyses) as mixtures of tetrahedral and octahedral Mo(VI) species (with O-donor ligands) in various ratios, which were dependent on the nature of the medium rather than that of the initial Mo(VI) compounds. Red blood cells take up Mo(VI) predominantly in the form of [MoO(4)](2-). Implications of these results to the development of Mo(VI)-based anti-diabetics and to the mechanisms of natural uptake and metabolism of Mo(VI) are discussed.     

Synthesis, structure, and nuclease properties of several binary and ternary complexes of copper(II) with norfloxacin and 1,10 phenantroline

Three new binary Cu(II) complexes of norfloxacin have been synthesized and characterized. We also report the synthesis, characterization and X-ray crystallographic structures of a new binary compound, [Cu(HNor)(2)]Cl(2).2H(2)O (2) and two new ternary complexes norfloxacin-copper(II)-phen, [Cu(Nor)(phen)(H(2)O)](NO(3)).3H(2)O (4), and [Cu(HNor)(phen)(NO(3))](NO(3)).3H(2)O (5). The structure of 2 consists of two crystallographically independent cationic monomeric units of [Cu(HNor)(2)](2+), chloride anions, and uncoordinated water molecules. The Cu(II) ion is placed at a center of symmetry and is coordinated to two norfloxacin ligands which are related through the inversion center. The structures of 4 and 5 consist of cationic units ([Cu(Nor)(phen)(H(2)O)](+) for 4 and [Cu(HNor)(phen)(NO(3))](+) for 5), nitrate counteranions, and lattice water molecules that provide crystalline stability through a network of hydrogen-bond interactions. The complexes exhibit a five coordinated motif in a square pyramidal environment around the metal center. The ability of compounds 4 and 5 to cleave DNA has also been studied. Mechanistic studies with different inhibiting reagents reveal that hydroxyl radicals, singlet oxygen, and superoxide radicals are all involved in the DNA scission process mediated by these compounds.     

Synthesis, structure and spectroscopic properties of two models for the active site of the oxygenated state of cytochrome P450 [corrected

Two dioxygen adducts of thiolato-iron(II) porphyrins, [K(222)][Fe(TPpivP)(SC6HF4)(O2)] 1a and [Na(18c.6)][Fe(TPpivP)(SC6HF4)(O2)] 2 were synthesized by reaction of O2 with five-coordinate, high-spin, cryptated alkali metal thiolato-iron(II) 'picket fence' porphyrinate. They were characterized by visible and infrared spectroscopy: lambda max (log epsilon) = 360 nm (4), 427 nm (4.69), 560 nm (3.69), 610 nm (3.40) for both compounds; v(16O-16O) = 1139 cm-1 in chlorobenzene and fluorobenzene for 1a and 2. Single crystals of composition [K(222)][Fe(TPpivP)(SC6HF4)(O2)].[K(222)](SC6HF4)(C 6H5Cl)(H2O) 1b were obtained by diffusion of pentane/xylene mixtures into chlorobenzene solutions of 1a at -5 degrees C. Single crystals of composition [Na(18c.6)][Fe(TPpivP)(SC6HF4)(O2)] were obtained by slow diffusion of pentane into benzene solutions of 2. Structures of 1b and 2 were studied at 20 degrees C (1b) and -100 degrees C (1b and 2). 1b: space group P2(1)/c (monoclinic), a = 16.806(5) A (1.6806 nm), b = 14.331(4) A (1.4331 nm), c = 52.000(15) A (5.2000 nm), beta = 92.95(2) degrees, V = 12.507 A3 (12.507 nm3), Z = 4, Dcal = 1.28 g.cm-3 (t = 20 degrees C). The final R1 factor was 0.085 for 5238 reflections having I greater than 3 sigma(I). 2: space group P2(1)/c (monoclinic), a = 13.107(3) A (1.3107 nm), b = 27.055(4) A (2.7055 nm), c = 25.029(4) A (2.5029 nm), beta = 96.84(2) degrees, V = 8812 A3 (8.812 nm3), Z = 4, Dcal = 1.18 g.cm-3 (t = -100 degrees C). The final R1 factor was 0.088 for 6587 reflections having I greater than 3 sigma(I). The iron atom is, in both compounds, bonded to the four porphyrinato nitrogens (Np), the sulfur atom of the axial thiolate and one oxygen atom of the axially end-on bonded dioxygen molecule. The average Fe-Np distance found in 1b [1.994(4) A, 0.1994 nm] is not significantly different from that found in 2 [1.993(3) A, 0.1993 nm]. The Fe-S bond length is 2.367(3) A (0.2367 nm) in 1b and 2.365(2) A (0.2365 nm) in 2. The Fe-O1 distances with the oxygen atom of O2 bonded to iron are respectively 1.837(9) A (0.1837 nm) and 1.850(4) A (0.1850 nm). The end-on bonded O2 molecule is disordered in both complexes 1b and 2.(ABSTRACT TRUNCATED AT 400 WORDS)     

Characterization and crystal structure of cadmium(II) halide complexes with amino acids and their derivatives: VII. Crystal structures of aquadibromo(3-aminopropanoic acid)cadmium(II), dichloro(4-aminobutanoic acid)cadmium(II), diaquabis(aminohexanoic acid)cadmium(II) tetrachlorocadmium(II), and dibromo(azetidine-3-carboxylic acid)cadmium(II)

Seven cadmium complexes: [CdX2(Hapro)(H2O)n] (X: Cl(1), Br(2)), [CdX2(Hgaba)] (X: Cl(3), Br(4)), [Cd(Hahex)2(H2O)2][CdCl4] (5), and [CdX2(Haze-3)](H2O)n (X: Cl(6), Br(7)) have been prepared and investigated by means of IR and FT Raman spectra. The crystal and molecular structures of 2, 3, 5 and 7 were determined by a single-crystal X-ray diffraction method. In complex 2, the cadmium atom is in a distorted octahedral geometry, ligated by two carboxyl oxygen atoms of Hapro, a water molecule, and three bromine atoms; one is terminal and each of the other two is bridging two cadmium atoms to make a polymer. The structure of 3 consists of one-dimensional polymers bridged by two chlorine atoms and a carboxyl group. The carboxyl oxygen atoms of Hgaba coordinate forkedly to two cadmium atoms. The cadmium atom of [Cd(Hahex)2(H2O)2]2+ in complex 5 is in a distorted octahedral geometry, ligated by four carboxyl oxygen atoms of two molecules of Hahex and by two water molecules. [Cd(Hahex)2(H2O)2]2+ exists between two layers which are formed of infinite [CdCl4]2- chains. The carboxyl oxygen atoms of Hahex coordinate to the same cadmium atom. In complex 7, the cadmium atom is ligated by two carboxyl oxygen atoms and four bridging bromine atoms to make a polymer.     

Synthesis, structural characterization, antiradical and antidiabetic activities of copper(II) and zinc(II) Schiff base complexes derived from salicylaldehyde and beta-alanine

A series of copper(II) and zinc(II) complexes involving a tridentate O,N,O'-donor Schiff base derived from salicylaldehyde and beta-alanine {i.e. N-salicylidene-beta-alanine(2-), (L)}, having the composition [Cu(2)(L)(2)(H(2)O)].H(2)O (1), [Cu(L)(H(2)O)](n) (2), and [Zn(L)(H(2)O)](n) (3), have been prepared and characterized by elemental analyses, UV-visible (UV-VIS), FT-IR and ESI-MS spectra, and thermal analyses. Complexes 1 and 2 have been investigated by single crystal X-ray analysis and also by temperature dependent magnetic susceptibility measurements (294-80K). All prepared complexes have been evaluated by the antiperoxynitrite activity assay and alloxan-induced diabetes model. The significant antioxidant and antidiabetic activities have been found in the case of both copper(II) complexes 1 and 2. In spite of first two complexes, the zinc(II) complex 3, as well as the potassium salt of the ligand (KHL) showed only insignificant protective effect against the tyrosine nitration in vitro.     

In vitro study of the insulin-mimetic behaviour of vanadium(IV, V) coordination compounds

A representative set of vanadium(IV and V) compounds in varying coordination environments has been tested in the concentration range 1 to 10(-6) mM, using transformed mice fibroblasts (cell line SV 3T3), with respect to their short-term cell toxicity (up to 36 hours) and their ability to stimulate glucose uptake by cells. These insulin-mimetic tests have also been carried out with non-transformed human fibroblasts (cell line F26). The compounds under investigation comprise established insulin-mimetic species such as vanadate ([H(2)VO(4)](-)), [VO(acetylacetonate)(2)], [VO(2)(dipicolinate)](-) and [VO(maltolate)(2)], and new systems and coordination compounds containing OO, ON, OS, NS and ONS donor atom sets. A vitality test assay, measuring the reduction equivalents released in the mitochondrial respiratory chain by intracellular glucose degradation, is introduced and the results are counter-checked with (3)H-labelled glucose. Most compounds are toxic at the 1 mM concentration level, and most compounds are essentially non-toxic and about as effective as or more potent than insulin at concentrations of 0.01 mM and below. V(V) compounds tend to be less toxic than V(IV)compounds, and complexes containing thio functional ligands are somewhat more toxic than others. Generally, ON ligation is superior in insulin-mimetic efficacy to OO or O/ NS coordination, irrespective of the vanadium oxidation state. There is, however, no striking correlation between the nature of the ligand systems and the insulin-mimetic potency in these cell culture tests, encompassing 41 vanadium compounds, the results on 22 of which are reported in detail here. The syntheses and characteristics of various new compounds are provided together with selected speciation results. The crystal and molecular structures of [[VO(naph-tris)](2)] [where naph-tris is the Schiff base formed between o-hydroxynaphthaldehyde and tris(hydroxymethyl)amine] are reported. Electronic supplementary material to this paper can be obtained by using the Springer Link server located at http://dx.doi.org/10.1007/s00775-001-0311-5.     

Oxidation--reduction potentials of turkey liver xanthine dehydrogenase and the origins of oxidase and dehydrogenase behaviour in molybdenum-containing hydroxylases.

Redox potentials for the various centres in the enzyme xanthine dehydrogenase (EC 1.2.1.37) from turkey liver determined by potentiometric titration in the presence of mediator dyes, with low-temperature electron-paramagnetic-resonance spectroscopy. Values at 25 degrees C in pyrophosphate buffer, pH 8.2, are: Mo(VI)/Mo(V)(Rapid),-350 +/- 20mV; Mo(V) (Rapid)/Mo(IV), -362 +/- 20mV; Fe-S Iox./Fe-S Ired., -295 +/- 15mV; Fe-S IIox./Fe-S IIred., -292 +/- 15mV; FAD/FADH,-359+-20mV; FADH/FADH2, -366 +/- 20mV. This value of the FADH/FADH2 potential, which is 130mV lower than the corresponding one for milk xanthine oxidase [Cammack, Barber & Bray (1976) Biochem. J. 157, 469-478], accounts for many of the differences between the two enzymes. When allowance is made for some interference by desulpho enzyme, then differences in the enzymes' behaviour in titration with xanthine [Barber, Bray, Lowe & Coughlan (1976) Biochem. J. 153, 297-307] are accounted for by the potentials. Increases in the molybdenum potentials of the enzymes caused by the binding of uric acid are discussed. Though the potential of uric acid/xanthine (-440mV) is favourable for full reduction of the dehydrogenase, nevertheless, during turnover, for kinetic reasons, only FADH and very little FADH2 is produced from it. Since only FADH2 is expected to react with O2, lack of oxidase activity by the dehydrogenase is explained. Reactivity of the two enzymes with NAD+ as electron acceptor is discussed in relation to the potentials.     

Synthesis,crystal structure,and nuclease activity of planar mono-heterocyclic base copper(II) complexes

A series of mononuclear copper(II) complexes having a 1:1 molar ratio of copper and the planar heterocyclic base like 1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) are prepared from a reaction of copper(II) nitrate.trihydrate and the base (L) in ethanol or aqueous ethanol at different temperatures. The complexes [Cu(dpq)(NO(3))(2)] (2), [Cu(dpq)(NO(3))(H(2)O)(2)](NO(3)) (3), [Cu(dpq)(NO(3))(2)(H(2)O)(2)].2H(2)O (4.2H(2)O) and [Cu(dppz)(NO(3))(2)(H(2)O)].H(2)O (5.H(2)O) have been characterized by X-ray crystallography. The crystal structures show the presence of the heterocyclic base in the basal plane. The coordination geometries of the copper(II) centers are axially elongated square-pyramidal (4+1) in 2, 3 and 5, and octahedral (4+2) in 4. The nitrate anion in the coordination sphere displays unidentate and bidentate chelating bonding modes. The axial ligand is either H(2)O or NO(3) in these structures giving a Cu-L(ax) distance of approximately 2.4 A. The one-electron paramagnetic complexes (mu approximately 1.8 mu(B)) exhibit axial EPR spectra in DMF glass at 77 K giving g(parallel)>g( perpendicular ) with an A(parallel) value of approximately 170G indicating a [d(x)2(-y)2](1) ground state. The complexes are redox active and display a quasireversible cyclic voltammetric response for the Cu(II)/Cu(I) couple near 0.0 V vs. SCE giving an order of the E(1/2) values as 5(dppz)>2-4 (dpq)>[Cu(phen)(2)(H(2)O)](2+)>1 (phen). The complexes bind to calf thymus DNA giving an order 5 (dppz)>2 (dpq)>[Cu(phen)(2)(H(2)O)](2+)>1 (phen). An effect of the extended planar ring in dpq and dppz is observed in the DNA binding. The complexes show nuclease activity with pUC19 supercoiled DNA in DMF/Tris-HCl buffer containing NaCl in presence of mercaptopropanoic acid as a reducing agent. The extent of cleavage follows the order: [Cu(phen)(2)(H(2)O)](ClO(4))(2)>5>2 approximately 3 approximately 4>1. The bis-phen complex is a better cleaver of SC DNA than 1-5 having mono-heterocyclic base. Mechanistic investigations using distamycin reveal minor groove biding for the phen, dpq complexes, and a major groove binding for the dppz complex 5. The cleavage reactions are found to be inhibited in the presence of hydroxyl radical scavenger DMSO and the reactions are proposed to proceed via sugar hydrogen abstraction pathway. The ancillary ligand is found to have less effect in DNA binding but are of importance in DNA cleavage reactions.     

Equilibrium characterization of the As(III)-cysteine and the As(III)-glutathione systems in aqueous solution

Some arsenic compounds were the first antimicrobial agents specifically synthesized for the treatment of infectious diseases such as syphilis and trypanosomiasis. More recently, arsenic trioxide has been shown to be efficient in the treatment of acute promyelocytic leukemia. The exact mechanism of action has not been elucidated yet, but it seems to be related to arsenic binding to vicinal thiol groups of regulatory proteins. Glutathione is the major intracellular thiol and plays important roles in the cellular defense and metabolism. This paper reports on a study of the interactions between arsenic(III) and either cysteine or glutathione in aqueous solution. The behavior observed for the As(III)-glutathione system is very similar to that of As(III)-cysteine. In both cases, the formation of two complexes in aqueous solution was evidenced by NMR and electronic spectroscopies and by potentiometry. The formation constants of the cysteine complexes [As(H(-1)Cys)(3)], log K = 29.84(6), and [As(H(-2)Cys)(OH)(2)](-), log K = 12.01(9), and of the glutathione complexes [As(H(-2)GS)(3)](3-), log K = 32.0(6), and [As(H(-3)GS)(OH)(2)](2-), log K = 10(3) were calculated from potentiometric and spectroscopic data. In both cases, the [As(HL)(3)] species, in which the amine groups are protonated, predominate from acidic to neutral media, and the [As(L)(OH)(2)] species appear in basic medium (the charges were omitted for the sake of simplicity). Spectroscopic data clearly show that the arsenite-binding site in both complexes is the sulfur atom of cysteine. In the [As(L)(OH)(2)] species, the coordination sphere is completed by two hydroxyl groups. In both cases, arsenic probably adopts a trigonal pyramidal geometry. Above pH 10, the formation of [As(OH)(2)O](-) excludes the thiolates from arsenic coordination sites. At physiological pH, almost 80% of the ligand is present as [As(HL)(3)].     

Characterization and crystal structure of cadmium(II) halide complexes with amino acids and their derivatives VI. The comparison of crystal structures of cadmium(II) halide complexes with three kinds of piperidine carboxylic acids

Six cadmium(II) halide complexes with dl-piperidine-2-carboxylic acid (DL-Hpipe-2), dl-piperidine-3-carboxylic acid (DL-Hpipe-3), and piperidine-4-carboxylic acid (Hpipe-4), have been prepared and characterized by means of IR and Raman spectra and thermal analysis. The crystal structures of [CdCl2(DL-Hpipe-2)(H2O)], [CdBr2(DL-Hpipe-3)], and [CdCl2(Hpipe-4)] have been determined by X-ray diffraction. These three complexes have one-dimensional polymer structures bridged by halide atoms. The crystal of [CdCl2(DL-Hpipe-2)(H2O)] is orthorhombic with the space group Pca2(1). The cadmium atom is in an octahedral geometry, ligated by a carboxyl oxygen atom, two bridging chlorine atoms, a terminal chlorine atom, a water molecule and a carboxyl oxygen atom of a neighboring molecule. The carboxyl oxygen atoms of DL-Hpipe-2 are coordinated to two cadmium atoms. The unit cell consists of two types of one-dimensional polymer structures: [CdCl2(D-Hpipe-2)(H2O)] and [CdCl2(L-Hpipe-2)(H2O)]. Therefore, it is better to write [CdCl2(DL-Hpipe-2)(H2O)] as [CdCl2(D-Hpipe-2)(H2O)][CdCl2(L-Hpipe-2)(H2O)]. The crystal structure of [CdBr2(DL-Hpipe-3)] is monoclinic with space group P2(1). The cadmium atom is in a distorted octahedral geometry ligated by two carboxyl oxygen atoms and four bridging bromine atoms. This complex consists of either D-Hpipe-3 or L-Hpipe-3. Therefore [CdBr2(DL-Hpipe-3)] is written as [CdBr2(D or L-Hpipe-3)]. The crystal of [CdCl2(Hpipe-4)] is monoclinic with space group P2(1)/n. The structure is similar to that of [CdBr2(D or L-Hpipe-3)].