Altered expression of HES-1, BETA2/NeuroD, and PDX-1 is involved in impaired insulin synthesis induced by glucocorticoids in HIT-T15 cells

Rat tail tendon (RTT) collagen has been reacted with a homologous series of chromium(III) complexes viz., (H2O)(4)Cr(OH)(2)Cr(H2O)(4+)(4) 1 (dimer), Cr(3)(OH)(4)(H2O)(5+)(9) 2 (trimer), and Cr(4)(OH)(4)(O2)(H2O)(4+)(12) 3 (tetramer), and the structural alterations brought about by these complexes have been investigated through atomic force microscopy (AFM) and circular dichroism (CD) studies. Examination of Cr(III)-treated tendons using AFM revealed changes in the D-periodicity of collagen, which may arise due to differences in the topological distribution of various Cr(III) complexes. Evidence for organisation of monomeric collagen into quarter staggered fibrils in the presence of Cr(III) dimer, 1, has been obtained. The quaternary structural changes induced by chromium in the protein have been correlated to the conformational changes of collagen in the absence of denaturation.     

Solution structural studies of molybdate-nucleotide polyanions

The complexation of molybdate with the nucleotides adenosine-5'-monophosphate (5'-AMP), adenosine-3'-monophosphate (3'-AMP) and guanosine-5'-monophosphate (5'-GMP) has been investigated by (1)H and (31)P NMR and Mo K-edge X-ray absorption near edge (XANES) and extended X-ray absorption fine structure (EXAFS) spectroscopy. Acidification of aqueous solutions containing molybdate and each of the nucleotides resulted in the formation of a single species characterized by (1)H resonances which are deshielded relative to those of free nucleotide. Analysis of the two-component systems indicated a Mo/nucleotide ratio of 2.5:1 for the complexation species. White compounds, characterized as Na(2)[Mo(5)O(15)(HB)(2)] (B=5'-AMP, 5'-GMP), have been isolated from the acidified molybdate/H(2)B solutions. Dissolution in D(2)O replicates the NMR spectra of the solution species observed prior to precipitation. Solution and solid state Mo K-edge XAS and EXAFS spectroscopy of Na(2)[Mo(5)O(15)(HAMP)(2)] and Na(6)[Mo(5)O(15)(PO(4))(2)] provide convincing evidence for the presence of a pentamolybdodiphosphate core in the molybdate-nucleotide complexes in both the solid and solution states.     

Three new Cu(II) and Cd(II) complexes with 3-(2-pyridyl)pyrazole-based ligand: syntheses, crystal structures, and evaluations for bioactivities

Three new complexes [Cu(L)(2)(NO(3))](NO(3))(H(2)O)(1/2)(CH(3)OH)(1/2) (1), [Cd(L)(2)(NO(3))(2)](H(2)O)(3) (2) and [Cd(L)(2)(ClO(4))(CH(3)OH)](ClO(4))(H(2)O)(1/4)(CH(3)OH) (3) (L=1-[3-(2-pyridyl)pyrazol-1-ylmethyl]naphthalene) were synthesized and characterized by elemental analyses, IR and X-ray diffraction analysis. Among them, the Cu(II) and Cd(II) ions were both coordinated by four N donors from two distinct L ligands via N,N-bidentate chelating coordination mode. Additional weak interactions, such as the face-to-face pi-pi stacking and C-Hcdots, three dots, centeredO H-bonding interactions, linked the mononuclear unit into 1D chain and further into 2D network. Complexes 1-3 were subjected to biological assays in vitro against six different cancer cell lines. All of them exhibited cytotoxic specificity and notable cancer cell inhibitory rate. The interactions of 1-3 with calf thymus DNA were investigated by thermal denaturation, viscosity measurements, spectrophotometric and electrophoresis methods. The results indicate that these complexes bound to DNA by intercalation mode via the ligand L and had different nuclease activities, which were in good agreement with their DNA-binding strength. Moreover, the central metal ions of 1-3 played a vital role in DNA-binding behaviors, DNA-cleavage activities and cytotoxicities, whereas the contribution of the different counter anions to their bioactivities also should not be ignored.     

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.     

Uracilato and 5-halouracilato complexes of Cu(II), Zn(II) and Ni(II). X-ray structures of [Cu(uracilato-N(1))(2)(NH(3))(2)].2(H(2)O), [Cu(5-chlorouracilato-N(1))(2)(NH(3))(2)](H(2)O)(2), [Ni(5-chlorouracilato-N(1))(2)(en)(2)].2H(2)O and [Zn(5-chlorouracilato-N(1))(NH(3))(3)].(5-chlorouracilato-N(1)).(H(2)O)

Four new complexes of uracilato and 5-halouracilato with the divalent metal ions Cu(II), Zn(II) and Ni(II) were obtained and structurally characterized. [Cu(uracilato- N(1))(2)(NH(3))(2)].2(H(2)O) (1) and [Cu(5-chlorouracilato-N(1))(2)(NH(3))(2)](H(2)O)(2) (2) complexes present distorted square planar co-ordination geometry around the metal ion. Although an additional axial water molecule is present [Cu(II)-OH(2)=2.89 A (for 1) and 2.52 A (for 2)] in both cases, only in the complex 2 would be considered in the limit of a bond distance. The Zn(II) in [Zn(5-chlorouracilato-N(1))(NH(3))(3)].(5-chlorouracilato-N(1)).(H(2)O) presents a tetrahedral co-ordination with three ammonia molecules and the N(1) of the corresponding uracilato moiety. A non-coordinated uracilato molecule is present as a counterion and a recognition between co-ordinated and free ligands, by means a tandem of H-bonds, should be mentioned. Finally, the complex [Ni(5-chlorouracilato-N(1))(2)(en)(2)] (H(2)O)(2) (where en is ethylenediamine) presents a typical octahedral trans co-ordination with additional hydrogen bonds between 5-chlorouracilato and the NH(2) groups of ethylenediamine units.     

Molecular structure, bioavailability and bioactivity of [Cu(o-phen)2(cnge)](NO3)2.2H2O and [Cu(o-phen)(cnge)(H2O)(NO3)2] complexes

Two Cu(II) complexes with cyanoguanidine (cnge) and o-phenanthroline, [Cu(o-phen)(2)(cnge)](NO(3))(2).2H(2)O (1) and [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)] (2), have been synthesized using different experimental techniques and characterized by elemental analyses, FTIR, diffuse and UV-vis spectra and EPR and magnetic moment measurements techniques. The crystal structures of both complexes were solved by X-ray diffraction methods. Complex (1) crystallizes in the monoclinic space group C2/c with a=12.621(5), b=31.968(3), c=15.39(1)A, beta=111.68(4) degrees, and Z=8 and complex (2) in the monoclinic space group P2(1)/n with a=10.245(1), b=13.923(2), c=12.391(2)A, beta=98.07(1) degrees, and Z=4. The environments of the copper(II) center are trigonal bipyramidal (TBP) for [Cu(o-phen)(2)(cnge)](2+) and an elongated octahedron for [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)]. Solution studies have been performed to determine the species distribution. The superoxide dismutase (SOD) activities of both complexes have also been tested in order to determine if these compounds mimic the enzymatic action of the enzyme SOD that protects cells against peroxide radicals.     

Influence of protic ionic liquids on the structure and stability of succinylated Con A

We report the synthesis of a series of ionic liquids (ILs) from various ions having different kosmotropicity including dihydrogen phosphate (H(2)PO(4)(-)), hydrogen sulfate (HSO(4)(-)) and acetate (CH(3)COO(-)) as anions and chaotropic cation such as trialkylammonium cation. To characterize the biomolecular interactions of ILs with protein, we have explored the stability of succinylated Con A (S Con A) in the presence of these aqueous ILs, which are varied combinations of kosmotropic anion with chaotropic cation such as triethylammonium dihydrogen phosphate [(CH(3)CH(2))(3)NH][H(2)PO(4)] (TEAP), trimethylammonium acetate [(CH(3))(3)NH][CH(3)COO] (TMAA), trimethylammonium dihydrogen phosphate [(CH(3))(3)NH][H(2)PO(4)] (TMAP) and trimethylammonium hydrogen sulfate [(CH(3))(3)NH][HSO(4)] (TMAS). Circular dichroism (CD) and fluorescence experiments have been used to characterize the stability of S Con A by ILs. Our data distinctly demonstrate that the long alkyl chain IL TEAP is a strong stabilizer for S Con A. Further, our experimental results reveal that TEAP is an effective refolding enhancer for S Con A from a thermally denatured protein structure.     

Synthesis, crystal structure, magnetic property and oxidative DNA cleavage activity of an octanuclear copper(II) complex showing water-perchlorate helical network

A new octanuclear copper(II) complex has been synthesized and structurally characterized by X-ray crystallography: [Cu(8)(HL)(4)(OH)(4)(H(2)O)(2)(ClO(4))(2)].(ClO(4))(2).2H(2)O (1) (H(3)L=2,6-bis(hydroxyethyliminoethyl)-4-methyl phenol). The complex is formed by the linkage of two terminal bimetallic cationic units and a tetranuclear mu(3)-hydroxo bridged dicubane core by a very short intramolecular hydrogen bond (O-H...O, 1.48(3)A and the angle 175 degrees). The coordination sphere of the terminal copper atoms is square pyramidal, the apical positions being occupied by water and a perchlorate ion. Complex 1 self-assembles to form a new type of water-perchlorate helical network [(H(2)O)(2)(ClO(4))](infinity) involving oxygen atoms of coordinated perchlorate ion and the two lattice water molecules through hydrogen-bonding interaction. The variable temperature-dependent susceptibility measurement (2-300K) of 1 reveals a strong antiferromagnetic coupling, J(1)=-220cm(-1) and J(2)=-98cm(-1) (J(1) and J(2) representing the exchange constant within [Cu(2+)](4) and [Cu(2+)](2) units, respectively). The complex binds to double-stranded supercoiled plasmid DNA giving a K(app) value of 1.2x10(7)M(-1) and displays efficient oxidative cleavage of supercoiled DNA in the presence of H(2)O(2) following a hydroxyl radical pathway.     

Requirement of calcium and phosphate ions in expression of sodium-dependent vitamin C transporter 2 and osteopontin in MC3T3-E1 osteoblastic cells

Osteoclasts dissolve mineralized bone matrix at bone resorption sites and release large amounts of calcium (Ca(2+)) and phosphate (PO(4)(3-)) ions into the extracellular fluid. However, the exact nature of Ca(2+) and PO(4)(3-) on osteoblasts remains unclear. We proposed that Ca(2+) and PO(4)(3-) ions are required for the expression of sodium-dependent vitamin C transporter (SVCT) 2 and a differentiation marker, osteopontin (OPN), in osteoblasts as a response to the osteoclastic degradation. Results from Northern blotting indicated that a deficiency of Ca(2+) or PO(4)(3-) inhibited both SVCT2 and OPN expression in a time-dependent manner, whereas elevated Ca(2+) (1 to 4 mM) or PO(4)(3-) (1 to 4 mM) dose-dependently induced SVCT2, OPN expression and OPN promoter activity. In addition, the L-type calcium channel blocker, nifedipine (5 to 20 micro M) and the phosphate transporter inhibitor, foscarnet (0.15 to 0.6 mM), dose-dependently abolished Ca(2+)- and PO(4)(3-)-induced SVCT2, OPN expression and OPN promoter activity. Furthermore, the results from L-ascorbic acid uptake assay and Western blotting indicated that the stimulatory effect of Ca(2+) and PO(4)(3-) on functional SVCT2 protein expression. These findings suggested that Ca(2+) and PO(4)(3-) regulate osteoblastic phenotype by entering into cells to stimulate SVCT2 and OPN expression.     

Protein degradation by peroxide catalyzed by chromium (III): role of coordinated ligand

In order to understand the role of coordinated ligands in controlling the biotoxicity of chromium (III), interactions of three types of chromium (III) complexes viz. trans-diaquo [1,2 bis (salicyledeneamino) ethane chromium (III) perchlorate, [(Cr(salen)(H(2)O)(2)](ClO(4)); tris (ethylenediamine) chromium (III) chloride, [Cr(en)(3)]Cl(3), and monosodium ethylene diamine tetraacetato monoaquo chromiate (III), [Cr(EDTA)(H(2)O)]Na with BSA has been investigated. Spectroscopic and equilibrium dialysis studies show that the two cationic complexes Cr(salen)(H(2)O)(+)(2) and Cr(en)(3+)(3) bind to the protein with a protein-metal ratio of 1:8 and 1:4. The anionic complex Cr(EDTA)(H(2)O)(-) binds to the protein with a protein-metal ratio of 1:2. The binding constant K(b) as estimated from the fluorescence quenching studies has been found to be 7.6 +/- 0.4 x 10(3) M(-1), 3.1 +/- 0.2 x 10(2) M(-1), and 1.8 +/- 0.2 x 10(2) M(-1) for Cr(salen)(H(2)O)(+)(2), Cr(en)(3+)(3), and Cr(EDTA)(H(2)O)(-) respectively indicating that the thermodynamic stability of protein-chromium complex is Cr(salen)(H(2)O)(+)(2) > Cr(en)(3+)(3) approximately Cr(EDTA)(H(2)O)(-). The complexes Cr(salen)(H(2)O)(+)(2) and Cr(EDTA)(H(2)O)(-) in the presence of hydrogen peroxide have been found to bring about protein degradation, whereas Cr(en)(3+)(3) does not bring about any protein damage. This clearly shows that the nature of the chromium (III) complex plays a major role in the biotoxicity of chromium (III).     

Copper(II)-cis,cis-1,3,5-triaminocyclohexane complex-promoted hydrolysis of dipeptides: kinetic, speciation and structural studies

The hydrolysis of glycylglycine (GylGly), glycyl-L-leucine (GlyLeu), L-leucylglycine (LeuGly) and glycyl-DL-serine (GlySer) promoted by a copper(II)- cis, cis-1,3,5-triaminocyclohexane complex [Cu(II)TACH] was investigated at 70 degrees C and pH 7-10, using HPLC. The observed pseudo-first-order rate constants (k(obs)) and rate enhancing factors (REF) were as follows: 4.1x10(-3 )h(-1)(REF=23) for GylGly, 1.6x10(-3 )h(-1)(REF=21) for GlyLeu, 5.1x10(-3 )h(-1)(REF=64) for LeuGly and 9.2x10(-2 )h(-1)(REF=47) for GlySer [pH 8.1, dipeptide 2 mM, copper(II) 2 mM and TACH 2 mM]. Based on the pH dependence and dipeptide concentration dependence of the initial rates and speciation of the Cu(II)-TACH-dipeptide system at 25 degrees C and I=0.1, the reactions proceed via the formation of a ternary complex [Cu(TACH)(dipeptide)](+) as an intermediate followed by OH(-)-dependent and OH(-)-independent paths to give amino acid(s). GylGly, GlyLeu and LeuGly preferred the OH(-)-dependent path, while GlySer preferred the OH(-)-independent path. The latter can be explained by the intramolecular attack of the amide carbonyl group coordinated with its oxygen atom by the OH group in the serine residue. The X-ray crystal structure of [Cu(TACH)(GlyGly)]BPh(4).MeOH confirmed that GlyGly coordinates to copper(II) ion with its terminal amino N and amide O atoms. The crystal structures of [Cu(TACH)(Gly)]BPh(4) and [Cu(2)(TACH)(2)(OH)(2)](ClO(4))(2).NaClO(4).H(2)O are also reported.     

The preparation,characterisation and in vitro cytotoxicity of potentially chemotherapeutic heterobimetallic complexes containing early and late transition metals

The reactions of phosphine Ph(2)P(CH(2))(2)SO(3)Na with Cp(2)M'Cl(2) (M'=Ti, Zr) in aqueous solution give the metallophosphines, Cp(2)Ti(OSO(2)(CH(2))(2)PPh(2))(2) (Cp=cyclopentadienyl) and CpZr(OH)(OSO(2)(CH(2))(2)PPh(2))(2). These react with CODM"Cl(2) (M"=Pd, Pt) (COD=1,5-cyclooctadiene) in dichloromethane to give heterobimetallic complexes Cp(2)Ti(OSO(2)(CH(2))(2)PPh(2))(2)M"Cl(2) and CpZr(OH)(OSO(2)(CH(2))(2) PPh(2))(2)M"Cl(2) respectively. The compounds are characterised by infrared and NMR spectroscopies and elemental analysis. Electrospray mass spectra of the complexes are reported and compared to those of Cp(2)M'Cl(2) in water and dimethylsulfoxide (DMSO). For zirconocene dichloride and its product heterobimetallic complexes, the addition of ethylenediamine tetraacetic acid disodium salt (Na(2)H(2)EDTA) was found to be an effective ionisation enhancement agent for the electrospray mass spectral studies. Cytotoxicity studies for the previously reported Cl(2)Pt(PPh(2)(CH(2))(2)SO(3)H)(2).3.5H(2)O (Wedgwood et al., Inorg. Chim. Acta 290 (1999) 189), and the compounds Cp(2)Ti(OSO(2)(CH(2))(2) PPh(2))(2).1.5H(2)O and Cp(2)Ti(OSO(2)(CH(2))(2)PPh(2))(2)PtCl(2).4H(2)O reported here, have been evaluated by colony formation assay against cisplatin-sensitive and -resistant cell lines L929 and L929/R to highlight potential chemotherapeutic activity. The compound Cl(2)Pt(PPh(2)(CH(2))(2)SO(3)H)(2).3.5H(2)O overcomes cisplatin resistance.     

The interaction of 5-fluoroorotic acid with transition metals: synthesis and characterisation of Ni(II), Cu(II) and Zn(II) complexes

5-Fluoroorotic acid (H(3)FOro) is a potent inhibitor for some metalloproteins such as dihydroorotase and dihydroorotate dehydrogenase and for thymidylate synthase (nonmetalloprotein) in the human malaria parasite Plasmodium falciparum. To study the coordination chemistry of H(3)Foro, the ammonium salt [NH(4)(+)][H(2)FOro(-)].1H(2)O (1) and the first coordination compounds of H(3)FOro with transition metals [Ni(HFOro(2-))(H(2)O)(4)].1H(2)O (2), [Cu(HFOro(2-))(NH(3))(H(2)O)](n) (3) and [Cu(3)(FOro(3-))(2)(NH(3))(6)(H(2)O)(2)] (4) have been synthesised and characterised by single-crystal X-ray diffraction, IR spectroscopy and by thermogravimetry. Three different coordination modes of 5-fluoroorotic acid have been established. In all cases the ligand is chelated to the metal via an amido-nitrogen and a carboxylate-oxygen but for (3), there is also a carboxylate oxygen from another HFOro(2-) ligand resulting in a polymeric structure and for (4), the second amido-nitrogen in the ororotic acid ring coordinates to give a trinuclear complex. The metal coordination polyhedra are octahedral in (2), square-pyramidal in (3) and square-planar and approximately square-pyramidal in (4). An octahedral coordination geometry including a N(1)/O(61)-chelating HFOro(2-) ligand with four aqua ligands is proposed for the Zn complex [Zn(HFOro(2-)) (H(2)O)(4)].0.5H(2)O (5), based on IR and thermogravimetric data. Extensive hydrogen bonded networks and some ring-ring stacking interactions are observed in each of the structures.     

DNA cleavage studies of mononuclear and dinuclear copper(II) complexes with benzothiazolesulfonamide ligands

Copper-based transition metal complexes performing single- and double-strand scission of DNA have been studied. The dinuclear complexes [Cu(2)(L)(2)(OCH(3))(2)(NH(3))(2)] and [Cu(2)(L)(2)(OCH(3))(2)(DMSO)(2)] are more active than the corresponding mononuclear [Cu(L)(2)(py)(2)] (where HL= N-(4-methylbenzothiazol-2-yl)benzenesulfonamide), suggesting that the dinuclearity is an important factor in the oxidative cleavage of DNA. The cleavage efficiency of the complexes depends on the reducing agent used in the process, the tandem ascorbate/H(2)O(2) being the most efficient. PAGE analyses have shown that these complexes cleave DNA without sequence selectivity. The DNA degradation process takes place mainly by C1' oxidation, but C4' and C5' oxidations cannot be ruled out as minor pathways. These copper complexes preferably oxidize guanine under mild conditions, but under more drastic conditions the oxidation reactivity appears to be T>G>C>A, suggesting the intervention of hydroxyl radicals as active species.     

Spectroscopic and structural characterization of copper(II) and palladium(II) complexes of a lichen substance usnic acid and its derivatives. Possible forms of environmental metals retained in lichens

The metal binding properties of a phenolic lichen substance usnic acid (UA) and its acetyl and enamine derivatives 9-O-acetylusnic acid (MAUA), 7,9-di-O-acetylusnic acid (DAUA), Delta(2,11)-enaminousnic acid (EUA), and N-substituted Delta(2,11)-enaminousnic acids have been studied by synthetic and spectroscopic methods, and the structures of copper(II) and palladium(II) complexes have been established by the X-ray diffraction method. Cu(II) reacted with UA and DAUA to give the binary complexes Cu(UA)(2) x H(2)O and Cu(DAUA)(2), respectively, and Cu(bpy) (bpy=2,2'-bipyridine) formed ternary complexes with UA and DAUA. Pd(II) also reacted with UA, DAUA, EUA, and N-substituted Delta(2,11)-enaminousnic acids to give the corresponding binary complexes. All the isolated complexes are insoluble in water and soluble in most organic solvents. They exhibited very strong absorption and circular dichroism spectral peaks in the UV region. The (1)H-NMR spectrum in CDCl(3) of the Pd(II) complex of N-phenyl-Delta(2,11)-enaminousnic acid (PEUA), Pd(PEUA)(2) x C(6)H(6), showed that the C(4)-proton signal suffered a large upfield shift (0.86 ppm) due to the ring current effect of the N-phenyl moiety. X-Ray crystal structure analysis has been performed for Cu(bpy)(UA)(ClO(4)) x CH(3)OH, Pd(MEUA)(2) x C(6)H(6), and Pd(PEUA)(2) x C(6)H(6). Cu(bpy)(UA)(ClO(4)) x CH(3)OH has a square-pyramidal structure with the two nitrogen atoms of bpy and the two oxygen atoms of the mono-deprotonated B ring of UA in the equatorial positions, while Pd(II) binds with two molecules of MEUA or PEUA in the trans configuration through the nitrogen and oxygen atoms with deprotonation. The N-phenyl ring of PEUA in Pd(PEUA)(2).C(6)H(6) was revealed to be located close to the C(4) proton as indicated by (1)H-NMR. Isolation of Cu(2)(bpy)(2)(UA)(NO(3))(2) x 2H(2)O suggests that UA has two metal binding sites that can form polymeric complexes. The present results substantiate the metal binding ability and the structures of the complexes of usnic acid and other substances from lichens as biomonitors of environmental metal ions.     

Single diastereomers of unsymmetrical tris-spirocyclic cyclotriphosphazenes based on 1,1'-bi-2-naphthol--synthesis and structures

Diastereoselective synthesis and characterization of chiral unsymmetrical tris-spirocyclic cyclotriphosphazenes based on chiral 1,1'-bi-2-naphthol (BINOL) are reported. Specifically, the chiral compounds (-)N(3)P(3)[1,1'-O(2)(C(10)H(6))(2)](O-2,2'C(6)H(4)-C(6)H(4)O)Cl(2) [(-)-4] and (-)N(3)P(3)[1,1'-O(2)(C(10)H(6))(2)](OCH(2)CH(2)NMe)(2) [(-)-5] are prepared by starting with the chiral mono-spiro compound (-)N(3)P(3)[1,1'-O(2)(C(10)H(6))(2)]Cl(4) [(-)-3]. Synthesis of four other chiral spirocyclics, N(3)P(3)[1,1'-O(2)(C(10)H(6))(2)](OCH(2)CH(2) NMe)(O-2,2'C(6)H(4)-C(6)H(4)O)[(-)-6 and (+)-6], N(3)P(3)[1,1'-O(2)(C(10)H(6))(2)](NMe(2))(4) [(-)-7], N(3)P(3)[1,1'-O(2)(C(10)H(6))(2)](O-2,2'C(6)H(4)-C(6)H(4)O)(NMeCH(2)CH(2)OH)(2) [(-)-8 and (+)-8], and N(3)P(3)[1,1'-O(2)(C(10)H(6))(2)](O-2,2'C(6)H(4)-C(6)H(4)O)[NHCH(2)CH(2)CH(2)Si(OEt)(3)](2) (9) is also reported herein. Compounds 4-6 are obtained in the solid state diastereoselectively and their X-ray structures have been determined and discussed. The diastereoselectivity is also shown by structural characterization of two distinct isomers in the case of 6 [(-)-6 and (+)-6, respectively] by starting with precursor of 3 having (R) or (S)-BINOL residue. The (1)H NMR spectra of 7 and 8 exhibit doublets with virtual coupling for the methyl protons, consistent with the chiral nature of the binaphthoxy residue. The potential of 9, which hydrolyzes readily in CDCl(3) solution, as a useful precursor for chiral polymer applications is highlighted.     

Biomineralization of carbonate and phosphate by moderately halophilic bacteria

We investigated the precipitation of carbonate and phosphate minerals by 19 species of moderately halophilic bacteria using media with variable Mg(2+)/Ca(2+) ratios. The precipitated minerals were calcite, magnesium (Mg) calcite, and struvite (MgNH(4)PO(4) x 6H(2)O) in variable proportions depending on the Mg(2+)/Ca(2+) ratio of the medium. The Mg content of the Mg-calcite decreased with increasing Ca(2+) concentration in the medium. According to the saturation indices, other minerals could also have precipitated. We observed important differences between the morphology of carbonate and phosphate, which may help us to recognize these minerals in natural systems. We studied the growth and pH curves of four bacteria in media specific for carbonate and struvite precipitation. We consider the biomineralization processes that produce carbonate and phosphate minerals, and propose a hypothesis for the lack of struvite in natural environments and ancient rocks.     

Unusual coordinating behavior by three non-steroidal anti-inflammatory drugs from the oxicam family towards copper(II). Synthesis, X-ray structure for copper(II)-isoxicam, -meloxicam and -cinnoxicam-derivative complexes, and cytotoxic activity for a copper(II)-piroxicam complex

Cytotoxic tests recently performed at National Cancer Institute, NCI (USA), on [Cu(HPIR)(2)(DMF)(2)], 1, (H(2)PIR=piroxicam, 4-hydroxy-2-methyl-N-pyridin-2-yl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide) a widely used non-steroidal anti-inflammatory drug, NSAID [see R. Cini, G. Giorgi, A. Cinquantini, C. Rossi, M. Sabat, Inorg. Chem. 29 (1990) 5197-5200, for synthesis and structural characterization, DMF=dimethylformamide] (NSC #624662) by using a panel of ca. 50 human cancer cells, showed growth inhibition factor GI(50) values as low as 20microM against several cancer lines, with an average value 54.4microM. The activity of 1 is larger against ovarian cancer cells, non-small lung cancer cells, melanoma cancer cells, and central nervous system cancer cells. The widely used anticancer drug carboplatin (cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II)) (NSC #241240) has average GI(50) value of 102microM. The reactions of copper(II)-acetate with other NSAIDs from the oxicam family were tested and crystalline complexes were obtained and characterized. Isoxicam (H(2)ISO=4-hydroxy-2-methyl-N-(5-methylisoxazol-3-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide) produced [Cu(HISO)(2)].0.5DMF, 2.0.5DMF (DMF=dimethylfomamide). The coordination arrangement is square-planar and the HISO(-) anions behave as ambi-dentate chelators via O(amide),N(isoxazole) and O(enolate),O(amide) donors. Meloxicam (H(2)MEL=4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide) produced [Cu(HMEL)(2)(DMF)].0.25H(2)O, 3.0.25H(2)O. The coordination arrangement is square-pyramidal, the equatorial donors being O(amide),N(thiazole) from two HMEL(-) anions and the apical donor being O(DMF). Unexpectedly, cinnoxicam (HCIN=2-methyl-1,1-dioxido-3-[(pyridin-2-ylamino)carbonyl]-2H-1,2-benzothiazin-4-yl-(3-phenylacrylate)) produced [Cu(MBT)(2)(PPA)(2)] (MBT=3-(methoxycarbonyl)-2-methyl-2H-1,2-benzothiazin-4-olate 1,1-dioxide, PPA=3-phenyl-N-pyridin-2-ylacrylamide).     

Reduction of uranium(VI) phosphate during growth of the thermophilic bacterium Thermoterrabacterium ferrireducens

The thermophilic, gram-positive bacterium Thermoterrabacterium ferrireducens coupled organotrophic growth to the reduction of sparingly soluble U(VI) phosphate. X-ray powder diffraction and X-ray absorption spectroscopy analysis identified the electron acceptor in a defined medium as U(VI) phosphate [uramphite; (NH4)(UO2)(PO4) . 3H2O], while the U(IV)-containing precipitate formed during bacterial growth was identified as ningyoite [CaU(PO4)2 . H2O]. This is the first report of microbial reduction of a largely insoluble U(VI) compound.     

Synthesis, structure and biomimetic properties of Cu(II)-Cu(II) and Cu(II)-Zn(II) binuclear complexes: possible models for the chemistry of Cu-Zn superoxide dismutase

Four imidazolate-bridged binuclear copper(II)-copper(II) and copper(II)-zinc(II) complexes viz., [(Bipy)(2)Cu-Im-Cu(Bipy)(2)](ClO(4))(3).CH(3)OH, [(Phen)(2)Cu-Im-Cu(Phen)(2)](BF(4))(3).2CH(3)OH, [(Bipy)(2)Cu-Im-Zn(Bipy)(2)](BF(4))(3), and [(Phen)(2)Cu-Im-Zn(Phen)(2)](BF(4))(3), (Bipy=2,2'-Bipyridyl, Phen=1-10-Phenanthroline and Im=imidazolate ion) were synthesized as a possible models for superoxide dismutase (SOD). Complex [(Bipy)(2)Cu-Im-Cu(Bipy)(2)](ClO(4))(3).CH(3)OH has been structurally characterized. This complex crystallizes in the triclinic space group P1, with the unit parameters a=8.88(5) A, b=13.79(17) A, c=20.18(18) A, alpha=76.424(8)(o), beta=85.888(6)(o), gamma=82.213(7). The metal-nitrogen bond length from 1.972-2.273 A and the distance Cu-Cu is 5.92 A. The five-coordinate geometry about the copper(II) ion is square pyramidal. Magnetic moment and electron paramagnetic resonance (e.p.r.) spectral measurements of the homobinuclear complexes have shown an antiferromagnetic exchange interaction. From the e.p.r. and UV-Vis spectral measurement studies, these complexes have been found to be stable (pH 8.5-10.5 for 1, 10.5 for 2,3 and 8.5 for 4). These complexes catalyse the dismutation of superoxide radical (O(2)(-)) at biological pH. All the observations indicate that these complexes act as good possible models for superoxide dismutase.