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  Subjects -> CHEMISTRY (Total: 837 journals)
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INORGANIC CHEMISTRY (41 journals)

Acta Polymerica     Hybrid Journal   (Followers: 6)
Additives for Polymers     Full-text available via subscription   (Followers: 20)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 4)
Advances in Polymer Technology     Hybrid Journal   (Followers: 11)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 2)
Bioinorganic Chemistry and Applications     Open Access   (Followers: 4)
Comments on Inorganic Chemistry: A Journal of Critical Discussion of the Current Literature     Hybrid Journal  
Current Methods in Inorganic Chemistry     Full-text available via subscription  
European Journal of Inorganic Chemistry     Hybrid Journal   (Followers: 7)
European Polymer Journal     Hybrid Journal   (Followers: 43)
Heterocyclic Communications     Hybrid Journal   (Followers: 2)
High Performance Polymers     Hybrid Journal  
Indian Journal of Chemistry - Section A     Open Access   (Followers: 5)
Inorganic Chemistry     Full-text available via subscription   (Followers: 20)
Inorganic Chemistry Communications     Hybrid Journal   (Followers: 8)
Inorganic Chemistry Frontiers     Full-text available via subscription   (Followers: 1)
Inorganic Materials     Hybrid Journal   (Followers: 2)
Inorganic Materials: Applied Research     Hybrid Journal   (Followers: 1)
Inorganica Chimica Acta     Hybrid Journal   (Followers: 4)
Inorganics     Open Access  
International Journal of Inorganic Chemistry     Open Access   (Followers: 1)
JBIC Journal of Biological Inorganic Chemistry     Hybrid Journal   (Followers: 3)
Journal of Inorganic and Organometallic Polymers and Materials     Partially Free   (Followers: 7)
Journal of Inorganic Biochemistry     Hybrid Journal   (Followers: 2)
Journal of Inorganic Chemistry     Open Access   (Followers: 1)
Journal of Polymer Engineering     Hybrid Journal   (Followers: 9)
Journal of Polymers and the Environment     Hybrid Journal   (Followers: 3)
Journal of Separation Science     Hybrid Journal   (Followers: 9)
Metallodrugs     Open Access  
Open Journal of Inorganic Chemistry     Open Access   (Followers: 2)
Plasmas and Polymers     Hybrid Journal  
Polymer Bulletin     Hybrid Journal   (Followers: 7)
Polymer Composites     Hybrid Journal   (Followers: 10)
Polyoxometalate Chemistry     Open Access  
Reviews in Inorganic Chemistry     Hybrid Journal  
Russian Journal of Inorganic Chemistry     Hybrid Journal  
Studies in Inorganic Chemistry     Full-text available via subscription  
Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry     Hybrid Journal   (Followers: 3)
Topics in Inorganic and General Chemistry     Full-text available via subscription  
Zeitschrift für anorganische und allgemeine Chemie     Hybrid Journal   (Followers: 1)
Zeitschrift für Kristallographie - New Crystal Structures     Open Access  
Journal Cover   Journal of Inorganic Biochemistry
  [SJR: 0.96]   [H-I: 87]   [2 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0162-0134
   Published by Elsevier Homepage  [2812 journals]
  • Novel ruthenium(II) cyclopentadienyl thiosemicarbazone compounds with
           antiproliferative activity on pathogenic trypanosomatid parasites
    • Abstract: Publication date: Available online 30 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Mariana Fernández , Esteban Rodríguez Arce , Cynthia Sarniguet , Tânia S. Morais , Ana Isabel Tomaz , Claudio Olea Azar , Roberto Figueroa , J. Diego Maya , Andrea Medeiros , Marcelo Comini , M. Helena Garcia , Lucía Otero , Dinorah Gambino
      Searching for new prospective antitrypanosomal agents, three novel Ru(II)-cyclopentadienyl compounds, [Ru(η 5-C5H5)(PPh3)L], with HL=bioactive 5-nitrofuryl containing thiosemicarbazones were synthesized and characterized in the solid state and in solution. The compounds were evaluated in vitro on the blood circulating trypomastigote form of Trypanosoma cruzi (Dm28c strain), the infective form of T. brucei brucei (strain 427) and on J774 murine macrophages and human-derived EA.hy926 endothelial cells. The compounds were active against both parasites with IC50 values in the micromolar range. Interestingly, they are much more active on T. cruzi than previously developed Ru(II) classical and organometallic compounds with the same bioactive ligands. The new compounds showed moderate to very good selectivity towards the parasites in respect to mammalian cells. The global results point at [RuCp(PPh3)L2] (L2= N-methyl derivative of 5-nitrofuryl containing thiosemicarbazone and Cp=cyclopentadienyl) as the most promising compound for further developments (IC50 T. cruzi =0.41μM; IC50 T. brucei brucei =3.5μM). Moreover, this compound shows excellent selectivity towards T. cruzi (SI >49) and good selectivity towards T. brucei brucei (SI >6). In order to get insight into the mechanism of antiparasitic action, the intracellular free radical production capacity of the new compounds was assessed by ESR. DMPO (5,5-dimethyl-1-pirroline-N-oxide) spin adducts related to the bioreduction of the complexes and to redox cycling processes were characterized. In addition, DNA competitive binding studies with ethidium bromide by fluorescence measurements showed that the compounds interact with this biomolecule.
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      PubDate: 2015-07-03T06:26:52Z
       
  • Editorial Board
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148




      PubDate: 2015-06-24T14:30:42Z
       
  • Contents
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148




      PubDate: 2015-06-24T14:30:42Z
       
  • Preface for the JIB Special Issue for the 12th European Biological
           Inorganic Chemistry Conference (EuroBIC 12) in Zurich, Switzerland, August
           24–28, 2014
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Eva Freisinger , Roland Sigel



      PubDate: 2015-06-24T14:30:42Z
       
  • Rhenium(I) polypyridine dibenzocyclooctyne complexes as phosphorescent
           bioorthogonal probes: Synthesis, characterization, emissive behavior, and
           biolabeling properties
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Alex Wing-Tat Choi , Hua-Wei Liu , Kenneth Kam-Wing Lo
      We report the development of rhenium(I) polypyridine complexes appended with a dibenzocyclooctyne (DIBO) moiety as bioorthogonal probes for azide-modified biomolecules. Three phosphorescent rhenium(I) polypyridine DIBO complexes [Re(N^N)(CO)3(py-C6-DIBO)][CF3SO3] (py-C6-DIBO=3-(N-(6-(3,4:7,8-dibenzocyclooctyne-5-oxycarbonylamino)hexyl)aminocarbonyl)pyridine; N^N=1,10-phenanthroline (phen) (1a), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me4-phen) (2a), 4,7-diphenyl-1,10-phenanthroline (Ph2-phen) (3a)) and their DIBO-free counterparts [Re(N^N)(CO)3(py-C6-BOC)][CF3SO3] (py-C6-BOC=3-(N-(6-(tert-butoxycarbonylamino)hexyl)aminocarbonyl)pyridine; N^N=phen (1b), Me4-phen (2b), Ph2-phen (3b)) were synthesized and characterized. Upon photoexcitation, all the complexes displayed intense and long-lived yellow triplet metal-to-ligand charge-transfer (3MLCT) (dπ(Re)→π*(N^N)) emission. The DIBO complexes underwent facile reactions with benzyl azide in methanol at 298K with second-order rate constants (k 2) in the range of 0.077 to 0.091M−1 s−1. As revealed from SDS-PAGE analysis, the DIBO complexes can selectively label azide-modified proteins and the resulting bioconjugates displayed strong phosphorescence upon photoexcitation. Results of inductively coupled plasma mass spectrometry (ICP-MS) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays indicated that the DIBO complexes accumulated in Chinese Hamster Ovary (CHO) cells with considerable cytotoxic activity. Upon incubation of CHO cells with these complexes, relatively weak intracellular emission was observed. In contrast, upon pretreatment of the cells with 1,3,4,6-tetra-O-acetyl-N-azidoacetyl-d-mannosamine (Ac4ManNAz), intense emission was observed from the cell membrane and some internal compartments. The results suggest that the DIBO complexes are promising candidates for imaging azide-labeled biomolecules.
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      PubDate: 2015-06-24T14:30:42Z
       
  • Octahedral rhodium(III) complexes as kinase inhibitors: Control of the
           relative stereochemistry with acyclic tridentate ligands
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Stefan Mollin , Radostan Riedel , Klaus Harms , Eric Meggers
      Octahedral metal complexes are attractive structural templates for the design of enzyme inhibitors as has been demonstrated, for example, with the development of metallo-pyridocarbazoles as protein kinase inhibitors. The octahedral coordination sphere provides untapped structural opportunities but at the same time poses the drawback of dealing with a large number of stereoisomers. In order to address this challenge of controlling the relative metal-centered configuration, the synthesis of rhodium(III) pyridocarbazole complexes with facially coordinating acyclic tridentate ligands was investigated. A strategy for the rapid synthesis of such complexes is reported, the diastereoselectivities of these reactions were investigated, the structure of several complexes were determined by X-ray crystallography, the high kinetic stability of such complexes in thiol-containing solutions was demonstrated in 1H-NMR experiments, and the protein kinase inhibition ability of this class of complexes was confirmed. It can be concluded that the use of multidentate ligands is currently maybe the most practical strategy to avoid a large number of possible stereoisomers in the course of exploiting octahedral coordination spheres as structural templates for the design of bioactive molecules.
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      PubDate: 2015-06-24T14:30:42Z
       
  • Magnetic susceptibility of Mn(III) complexes of hydroxamate siderophores
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Stephen D. Springer , Alison Butler
      The hydroxamate siderophores putrebactin, desferrioxamine B, and desferrioxamine E bind Mn(II) and promote the air oxidation of Mn(II) to Mn(III) at pH>7.1. The magnetic susceptibility of the manganese complexes were determined by the Evans method and the stoichiometry was probed with electrospray ionization mass spectrometry (ESIMS). The room temperature magnetic moments (μeff) for the manganese complexes of desferrioxamines B and E were 4.85BM and 4.84BM, respectively, consistent with a high spin, d4, Mn(III) electronic configuration. The manganese complex of putrebactin had a magnetic moment of 4.98BM, consistent with incomplete oxidation of Mn(II), as confirmed by X band EPR spectroscopy. Mass spectra of the Mn(III) desferrioxamine B and E complexes showed complexes at m/z 613.26 and 653.26, respectively, consistent with 1:1 complexation. Mass spectral peaks for manganese putrebactin at m/z 797.31 and 1221.41 corresponds to 1:2 and 2:3 Mn:putrebactin complexation. This study directly confirms the Mn(III) oxidation state in hydroxamate siderophore complexes.
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      PubDate: 2015-06-24T14:30:42Z
       
  • Cellular organization of siderophore biosynthesis in Pseudomonas
           aeruginosa: Evidence for siderosomes
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Véronique Gasser , Laurent Guillon , Olivier Cunrath , Isabelle.J. Schalk
      Pyoverdine I (PVDI) and pyochelin (PCH) are the two major siderophores produced by Pseudomonas aeruginosa PAO1 to import iron. The biochemistry of the biosynthesis of these two siderophores has been described in detail in the literature over recent years. PVDI assembly requires the coordinated action of seven cytoplasmic enzymes and is followed by a periplasmic maturation before secretion of the siderophore into the extracellular medium by the efflux system PvdRT-OpmQ. PCH biosynthesis also involves seven cytoplasmic enzymes but no periplasmic maturation. Recent findings indicate that the cytoplasmic enzymes involved in each of these two siderophore biosynthesis pathways can form siderophore-specific multi-enzymatic complexes called siderosomes associated with the inner leaflet of the cytoplasmic membrane. This organization may optimize the transfer of the siderophore precursors between the various participating enzymes and avoid the diffusion of siderophore precursors, able to chelate metals, throughout the cytoplasm. Here, we describe these recently published findings and discuss the existence of these siderosomes in P. aeruginosa.
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      PubDate: 2015-06-24T14:30:42Z
       
  • Sunflower metallothionein family characterisation. Study of the Zn(II)-
           and Cd(II)-binding abilities of the HaMT1 and HaMT2 isoforms
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): M. Tomas , M.A. Pagani , C.S. Andreo , M. Capdevila , S. Atrian , R. Bofill
      Plant metallothioneins (MTs) constitute a family of small Cys-rich proteins capable of coordinating metal ions, significantly differing from microbial and animal MTs. They are divided into four subfamilies depending on the Cys pattern in their sequence. In this work, the MT system of the sunflower plant (Helianthus annuus) has been defined, with ten genes coding for MTs (HaMT) belonging to the four plant MT subfamilies; three HaMT1, four HaMT2, one HaMT3 and two HaMT4 isoforms. The gene expression pattern and capacity to confer metal resistance to yeast cells have been analysed for at least one member of each subfamily. The divalent metal ion-binding abilities of HaMT1-2 and HaMT2-1 (the isoforms encoded by the most abundantly expressed HaMT1 and HaMT2 isogenes) have been characterised, as HaMT3 and HaMT4 were previously studied. Those isoforms constitute an optimum material to study the effect of Cys number variability on their coordination abilities, as they exhibit additional Cys residues regarding the canonical Cys pattern of each subfamily. Our results show that the variation in the number of Cys does not drastically modify their M(II)-binding abilities, but instead modulates the degree of heterogeneity of the corresponding recombinant syntheses. Significantly, the Zn(II)–HaMT1 complexes were highly susceptible to proteolytic cleavage. The recombinant Cd–MT preparations of both isoforms exhibit significant acid-labile sulphide content-Cd6S8 or Cd7S7 species. Overall results suggest that HaMT2-1 is probably associated with Cd(II) detoxification, in contrast to HaMT1-2, which may be more related to physiological functions, such as metal ion transport and delivery.
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      PubDate: 2015-06-24T14:30:42Z
       
  • Spectroscopic studies on peptides and proteins with cysteine-containing
           heme regulatory motifs (HRM)
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Erik Schubert , Nicole Florin , Fraser Duthie , H. Henning Brewitz , Toni Kühl , Diana Imhof , Gregor Hagelueken , Olav Schiemann
      The role of heme as a cofactor in enzymatic reactions has been studied for a long time and in great detail. Recently it was discovered that heme can also serve as a signalling molecule in cells but so far only few examples of this regulation have been studied. In order to discover new potentially heme-regulated proteins, we screened protein sequence databases for bacterial proteins that contain sequence features like a Cysteine–Proline (CP) motif, which is known for its heme-binding propensity. Based on this search we synthesized a series of these potential heme regulatory motifs (HRMs). We used cw EPR spectroscopy to investigate whether these sequences do indeed bind to heme and if the spin state of heme is changed upon interaction with the peptides. The corresponding proteins of two potential HRMs, FeoB and GlpF, were expressed and purified and their interaction with heme was studied by cw EPR and UV–Visible (UV–Vis) spectroscopy.
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      PubDate: 2015-06-24T14:30:42Z
       
  • Photoinduced reduction of the medial FeS center in the hydrogenase small
           subunit HupS from Nostoc punctiforme
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Patrícia Raleiras , Leif Hammarström , Peter Lindblad , Stenbjörn Styring , Ann Magnuson
      The small subunit from the NiFe uptake hydrogenase, HupSL, in the cyanobacterium Nostoc punctiforme ATCC 29133, has been isolated in the absence of the large subunit (P. Raleiras, P. Kellers, P. Lindblad, S. Styring, A. Magnuson, J. Biol. Chem. 288 (2013) 18,345–18,352). Here, we have used flash photolysis to reduce the iron-sulfur clusters in the isolated small subunit, HupS. We used ascorbate as electron donor to the photogenerated excited state of Ru(II)-trisbipyridine (Ru(bpy)3), to generate Ru(I)(bpy)3 as reducing agent. Our results show that the isolated small subunit can be reduced by the Ru(I)(bpy)3 generated through flash photolysis.
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      PubDate: 2015-06-24T14:30:42Z
       
  • Synthesis, solution and crystal structure of the coenzyme B12 analogue
           Coβ-2′-fluoro-2′,5′-dideoxyadenosylcobalamin
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Miriam Hunger , Klaus Wurst , Bernhard Kräutler
      Crystal structure analyses have helped to decipher the mode of binding of coenzyme B12 (AdoCbl) in the active site of AdoCbl-dependent enzymes. However, the question of how such enzymes perform their radical reactions is still incompletely answered. A pioneering study by Gruber and Kratky of AdoCbl-dependent glutamate mutase (GLM) laid out a path for the movement of the catalytically active 5′-deoxyadenosyl radical, in which H-bonds between the protein and the 2′- and 3′-OH groups of the protein bound AdoCbl would play a decisive role. Studies with correspondingly modified coenzyme B12-analogues are of interest to gain insights into cofactor binding and enzyme mechanism. Here we report the preparation of Coβ-2′-fluoro-2′,5′-dideoxyadenosylcobalamin (2′FAdoCbl), which lacks the 2′-OH group critical for the interaction in enzymes. 2′FAdoCbl was prepared by alkylation of cob(I)alamin, obtained from the electrochemical reduction of aquocobalamin. Spectroscopic data and a single crystal X-ray analysis of 2′FAdoCbl established its structure, which was very similar to that one of coenzyme B12. 2′FAdoCbl is a 19F NMR active mimic of coenzyme B12 that may help to gain insights into binding interactions of coenzyme B12 with AdoCbl-dependent enzymes, proteins of B12 transport and of AdoCbl-biosynthesis, as well as with B12-riboswitches.
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      PubDate: 2015-06-24T14:30:42Z
       
  • An NMR study on the
           6,6′-(2-(diethylamino)ethylazanediyl)bis(methylene)bis(5-hydroxy-2-hydroxymethyl-4H-pyran-4-one)
           interaction with AlIII and ZnII ions
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Massimiliano Peana , Serenella Medici , Valeria Marina Nurchi , Joanna Izabela Lachowicz , Guido Crisponi , Miriam Crespo-Alonso , Maria Amelia Santos , Maria Antonietta Zoroddu
      Here we report about the complex formation among an amine-bearing bis-kojic acid, 6,6′-(2-(diethylamino)ethylazanediyl)bis(methylene)bis(5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) and two metal ions, the trivalent hard and not essential metal ion AlIII and the borderline and essential divalent metal ion ZnII. We carried out a thorough NMR study in order to reach the indispensable structural information on the behavior of these complexes in solution. A combination of 1D, 2D total correlation spectroscopy, heteronuclear single quantum coherence spectroscopy, nuclear Overhauser enhancement spectroscopy and rotating-frame Overhauser effect spectroscopy experiments was used to assign the signals of both free and metal-bound ligand at different pH values. Our results highlighted the different coordination behaviors of the ligand towards the different metal ions, depending on their hard or borderline character. The trivalent metal ion, AlIII, mainly forms dinuclear helicate complexes of M2L3 stoichiometry, and the coordination only involves both hydroxypyrone (O,O)-donor atoms. NMR data are in agreement with the presence of a rigid and symmetric structure of L9–AlIII complexes up to physiological pH. On the contrary, with the divalent metal ion, NMR data showed the coexistence of several species in solution though ZnII forms complexes of ML stoichiometry at physiological pH, where the metal coordination involves the nitrogen atoms of both the linker and the side-chain amine groups together with the oxygen atoms of phenolate groups. The in solution study will be of interest for providing an insight on the ligand bioavailability and on its behavior in the chelation treatments.
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      PubDate: 2015-06-24T14:30:42Z
       
  • CuII-selective bispidine–dye conjugates
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Dominik Brox , Peter Comba , Dirk-Peter Herten , Esther Kimmle , Michael Morgen , Carmen L. Rühl , Arina Rybina , Holger Stephan , Golo Storch , Hubert Wadepohl
      The substitution of tetradentate bispidine ligands with rhodamine and cyanine dye molecules, coupled to an amine donor, forming an amide as potential fifth donor, is described. Bispidines are known to lead to very stable CuII complexes, and the coordination to CuII was expected to efficiently quench the fluorescence of dye molecules. However, at physiological pH the amide is not coordinated, as shown by titration experiments and crystallographic structural data of three possible isomers of these complexes. This may be due to the specific cavity shape of bispidines and the Jahn–Teller lability of the CuII center. While CuII coordination in aqueous solution leads to efficient fluorescence quenching, experiments show that the complex stabilities are not large enough for CuII sensing in biological media, and possibilities are discussed, how this may be achieved by optimized bispidine–dye conjugates.
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      PubDate: 2015-06-24T14:30:42Z
       
  • Lights and shadows in the challenge of binding acyclovir, a synthetic
           purine-like nucleoside with antiviral activity, at an apical–distal
           coordination site in copper(II)-polyamine chelates
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Inmaculada Pérez-Toro , Alicia Domínguez-Martín , Duane Choquesillo-Lazarte , Esther Vílchez-Rodríguez , Josefa María González-Pérez , Alfonso Castiñeiras , Juan Niclós-Gutiérrez
      Several nucleic acid components and their metal complexes are known to be involved in crucial metabolic steps. Therefore the study of metal–nucleic acid interactions becomes essential to understand these biological processes. In this work, the synthetic purine-like nucleoside acyclovir (acv) has been used as a model of guanosine recognition with copper(II)-polyamine chelates. The chemical stability of the N9-acyclic arm in acv offers the possibility to use this antiviral drug to deepen the knowledge of metal–nucleoside interactions. Cu(II) chelates with cyclam, cyclen and trien were used as suitable receptors. All these copper(II) tetraamine chelates have in common the potential ability to yield a Cu–N7(apical) bond assisted by an appropriate (amine)N–H⋯O6(acv) intra-molecular interligand interaction. A series of synthesis afforded the following compounds: [Cu(cyclam)(ClO4)2] (1), {[Cu(cyclam)(μ2-NO3)](NO3)}n (2), {[Cu(cyclam)(μ2-SO4)]·MeOH}n (3), {[Cu(cyclam)(μ2-SO4)]·5H2O}n (4), [Cu(cyclen)(H2O)]SO4·2H2O (5), [Cu(cyclen)(H2O)]SO4·3H2O (6), [Cu(trien)(acv)](NO3)2·acv (7) and [Cu(trien)(acv)]SO4·0.71H2O (8). All these compounds have been characterized by X-ray crystallography and FT-IR spectroscopy. Our results reveal that the macrochelates Cu(cyclen)2+ and Cu(cyclam)2+ are unable to bind acv at an apical site. In contrast, the Cu(trien)2+ complex has proved to be an efficient receptor for acv in compounds (7) and (8). In the ternary complex [Cu(trien)(acv)]2+, the metal binding pattern of acv consists of an apical Cu–N7 bond assisted by an intra-molecular (primary amino)N–H⋯O6(acv) interligand interaction. Structural comparisons reveal that this unprecedented apical role of acv is due to the acyclic nature of trien together with the ability of the Cu(trien)2+ chelate to generate five-coordinated (type 4+1) copper(II) complexes.
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      PubDate: 2015-06-24T14:30:42Z
       
  • Connectivity patterns and rotamer states of nucleobases determine
           acid–base properties of metalated purine quartets
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Marc Sven Lüth , Eva Freisinger , Gunnar Kampf , Marta Garijo Anorbe , Rolf Griesser , Bert P. Operschall , Helmut Sigel , Bernhard Lippert
      Potentiometric pH titrations and pD dependent 1H NMR spectroscopy have been applied to study the acidification of the exocyclic amino group of adenine (A) model nucleobases (N9 position blocked by alkyl groups) when carrying trans-a2PtII (with a=NH3 or CH3NH2) entities both at N1 and N7 positions. As demonstrated, in trinuclear complexes containing central A–Pt–A units, it depends on the connectivity pattern of the adenine bases (N7/N7 or N1/N1) and their rotamer states (head–head or head–tail), how large the acidifying effect is. Specifically, a series of trinuclear complexes with (A-N7)–Pt-(N7-A) and (A-N1)–Pt–(N1-A) cross-linking patterns and terminal 9-alkylguanine ligands (9MeGH, 9EtGH) have been analyzed in this respect, and it is shown that, for example, the 9MeA ligands in trans-,trans-,trans-[Pt(NH3)2(N7-9MeA-N1)2{Pt(NH3)2(9EtGH-N7)}2](ClO4)6·6H2O (4a) and trans-,trans-,trans-[Pt(NH3)2(N7-9EtA-N1)2{Pt(CH3NH2)2(9-MeGH-N7)}2](ClO4)6·3H2O (4b) are more acidic, by ca. 1.3units (first pK a), than the linkage isomer trans-,trans-,trans-[Pt(CH3NH2)2(N1-9MeA-N7)2{Pt(NH3)2(9MeGH-N7)}2](NO3)6·6.25H2O (1b). Overall, acidifications in these types of complexes amount to 7–9units, bringing the pK a values of such adenine ligands in the best case close to the physiological pH range. Comparison with pK a values of related trinuclear PtII complexes having different co-ligands at the Pt ions, confirms this picture and supports our earlier proposal that the close proximity of the exocyclic amino groups in a head–head arrangement of (A-N7)–Pt–(N7-A), and the stabilization of the resulting N6H–⋯H2N6 unit, is key to this difference.
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      PubDate: 2015-06-24T14:30:42Z
       
  • Properties of the indole ring in metal complexes. A comparison with the
           phenol ring
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Yuichi Shimazaki , Tatsuo Yajima , Osamu Yamauchi
      Tryptophan (Trp), an essential amino acid, has an indole ring with a high electron density and is frequently seen at the proximal position of the metal site in metalloproteins. For example, the indole ring of Trp has been reported to interact weakly with Cu(I) in a Cu chaperone CusF. Another aromatic amino acid, tyrosine (Tyr), has a phenol ring, which is an important metal binding site in various metalloproteins. Although the structures of the aromatic rings are different, they both have a weakly acidic moiety and perform some similar roles in biological systems, such as radical formation and electron transfer. In this review, we focus on these and other properties of the indole and phenol rings in metal-containing systems.
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      PubDate: 2015-06-24T14:30:42Z
       
  • A tridentate “click” nucleoside for metal-mediated base
           pairing
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Stefanie Litau , Jens Müller
      A new silver(I)-mediated base pair comprising an artificial nucleoside with the tridentate ligand 6-(1H-1,2,3-triazol-4-yl)-2,2′-bipyridine and a complementary imidazole nucleoside has been established within a B-DNA double helix. In the absence of any transition metal ion, a DNA duplex containing one such hetero base pair is slightly less stable than a comparable duplex with canonical base pairs. Upon the addition of AgNO3, a silver(I)-mediated base pair with a [3+1] coordination environment is formed, accompanied by an increase in thermal stability of about 5°C. UV and CD spectroscopic analyses provide clear proof for the coordination of the silver(I) ion to the DNA. In contrast, a DNA duplex comprising a central homo base pair of two 6-(1H-1,2,3-triazol-4-yl)-2,2′-bipyridine entities does not form a stabilizing metal-mediated base pair, as this would require a non-planar [3+3] coordination environment and a concomitant loss of π stacking interactions. The artificial nucleoside carrying the tridentate ligand belongs to a new family of “click” nucleosides, which are conveniently accessible from 2-deoxy-β-d-glycosyl azide via a copper-catalyzed Huisgen 1,3-dipolar cycloaddition with an alkyne-bearing ligand, and significantly extends the applicability of these “click” nucleosides.
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      PubDate: 2015-06-24T14:30:42Z
       
  • Copper(II) complexes with new fluoroquinolones: Synthesis, structure,
           spectroscopic and theoretical study, DNA damage, cytotoxicity and
           antiviral activity
    • Abstract: Publication date: Available online 23 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Sandra Dorotíková , Júlia Kožíšková , Michal Malček , Klaudia Jomová , Peter Herich , Kristína Plevová , Katarína Briestenská , Anna Chalupková , Jela Mistríková , Viktor Milata , Dana Dvoranová , Lukáš Bučinský
      Copper(II) complexes with fluoroquinolones in the presence of the nitrogen donor heterocyclic ligands 1,10-phenanthroline have been considered in detail. The phenanthroline moiety was introduced into the ligand environment with the aim to determine whether the nuclease activity is feasible. All suitable X-ray structures of the complexes under study reveal a distorted square pyramidal coordination geometry for Cu(II) atom. The conformational and spectroscopic (FT-IR and UV–visible) behavior has been analyzed and has been interpreted with respect to B3LYP/6-311G* calculations including molecular dynamics. The ability of the complexes to cleave DNA was studied by agarose gel electrophoresis with plasmid DNA pBSK+. The results have confirmed that the complexes under study behave as the chemical nucleases. Nuclease like activity in the absence of hydrogen peroxide allows us to deduce an interaction of the complexes with the DNA resulting in the conversion of supercoiled circular DNA to the nicked form. The DNA cleavage activity enhanced by the presence of hydrogen peroxide demonstrates the participation of reactive oxygen species, such as superoxide radical anions and hydroxyl radicals which presence was confirmed independently using the standard radical scavenging agents. It has been suggested that the radical formation through the Fenton/Haber–Weiss reaction is mediated by the redox cycling mechanisms with the participation of cupric/cuprous ions. Cytotoxic activity was evaluated as the 50% cytotoxic concentration (CC50). The potential effects of tested compounds on replication of murine gammaherpesvirus 68 (MHV-68) under in vitro conditions were also evaluated. However, no antiviral activity against MHV-68 was observed.
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      PubDate: 2015-06-24T14:30:42Z
       
  • Iron(II) porphyrins induced conversion of nitrite into nitric oxide: A
           computational study
    • Abstract: Publication date: Available online 22 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Ting Ting Zhang , Yong Dong Liu , Ru Gang Zhong
      Nitrite reduction to nitric oxide by heme proteins was reported as a protective mechanism to hypoxic injury in mammalian physiology. In this study, the pathways of nitrite reduction to nitric oxide mediated by iron(II) porphyrin (P) complexes, which were generally recognized as models for heme proteins, were investigated by using density functional theory (DFT). In view of two type isomers of combination of nitrite and Fe(II)(P), N-nitro- and O-nitrito-Fe(II)-porphyrin complexes, and two binding sites of proton to the different O atoms of nitrite moiety, four main pathways for the conversion of nitrite into nitric oxide mediated by iron(II) porphyrins were proposed. The results indicate that the pathway of N-bound Fe(II)(P)(NO2) isomer into Fe(III)(P)(NO) and water is similar to that of O-bound isomer into nitric oxide and Fe(III)(P)(OH) in both thermodynamical and dynamical aspects. Based on the initial computational studies of five-coordinate nitrite complexes, the conversion of nitrite into NO mediated by Fe(II)(P)(L) complexes with 14 kinds of proximal ligands was also investigated. Generally, the same conclusion that the pathways of N-bound isomers are similar to those of O-bound isomer was obtained for iron(II) porphyrin with ligands. Different effects of ligands on the reduction reactions were also found. It is notable that the negative proximal ligands can improve reactive abilities of N-nitro-iron(II) porphyrins in the conversion of nitrite into nitric oxide compared to neutral ligands. The findings will be helpful to expand our understanding of the mechanism of nitrite reduction to nitric oxide by iron(II) porphyrins.
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      PubDate: 2015-06-24T14:30:42Z
       
  • The key role of coligands in novel ruthenium(II)-cyclopentadienyl
           bipyridine derivatives: ranging from non-cytotoxic to highly cytotoxic
           compounds
    • Abstract: Publication date: Available online 20 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Leonor Côrte-Real , M. Paula Robalo , Fernanda Marques , Guilherme Nogueira , Fernando Avecilla , Tiago J.L. Silva , Filipa C. Santos , A. Isabel Tomaz , M. Helena Garcia , Andreia Valente
      A new family of eight ruthenium(II)-cyclopentadienyl bipyridine derivatives, bearing nitrogen, sulphur, phosphorous and carbonyl sigma bonded coligands, has been synthesized. Compounds bearing nitrogen bonded coligands were found to be instable in aqueous solution, while the others presented appropriate stabilities for the biologic assays and pursued for determination of IC50 values in ovarian (A2780) and breast (MCF7 and MDAMB231) human cancer cell lines. These studies were also carried out for the [ 5 :HSA] and [ 6 :HSA] adducts (HSA=Human Serum Albumin) and a better performance was found for the first case. Spectroscopic, electrochemical studies by cyclic voltammetry and Differential Functional Theory calculations allowed to get some understanding on the electronic flow directions within the molecules and to find a possible clue concerning the structural features of coligands that can activate bipyridyl ligands towards an increased cytotoxic effect. X-ray structure analysis of compound [Ru(η5-C5H5)(bipy)(PPh3)][PF6] ( 7 ; bipy=bipyridine) showed crystallization on C2/c space group with two enantiomers of the [Ru(η5-C5H5)(bipy)(PPh3)]+ cation complex in the racemic crystal packing.
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      PubDate: 2015-06-24T14:30:42Z
       
  • Cyclam glycoconjugates as lectin ligands and protective agents of
           metal-induced amyloid aggregation
    • Abstract: Publication date: Available online 19 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Valeria Lanza , Roberta D’Agata , Giuseppe Iacono , Francesco Bellia , Giuseppe Spoto , Graziella Vecchio
      Transition metal ion complexes of a number of chelators have been widely investigated due to their biological properties. The sugar conjugation of metal complexes has resulted in improved properties of the systems, such as solubility and lectin recognition. In this paper, we report the synthesis, the characterization of new glucose and galactose conjugates of 1,4,8,11-tetraazacyclotetradecane (cyclam) and their CuII complexes. The glycoconjugates were proved to be protective agents of metal-induced amyloid aggregation. The binding constants of the galactose conjugate KA1 =(3.07±0.16)×107 and KA2 =(2.13±0.04)×107 M−1 with the lectin Ricinus communis agglutinin (RCA120) as a model of galactose-specific human lectin were obtained with surface plasmon resonance.
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      PubDate: 2015-06-19T15:48:49Z
       
  • Electron Self-Exchange in Hemoglobins Revealed by Deutero-Hemin
           Substitution
    • Abstract: Publication date: Available online 18 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Navjot Singh Athwal , Jagannathan Alagurajan , Ryan Sturms , D. Bruce Fulton , Amy H. Andreotti , Mark S. Hargrove
      Hemoglobins (phytoglobins) from rice plants (nsHb1) and from the cyanobacterium Synechocystis (PCC 6803) (SynHb) can reduce hydroxylamine with two electrons to form ammonium. The reaction requires intermolecular electron transfer between protein molecules, and rapid electron self-exchange might play a role in distinguishing these hemoglobins from others with slower reaction rates, such as myoglobin. A relatively rapid electron self-exchange rate constant has been measured for SynHb by NMR, but the rate constant for myoglobin is equivocal and a value for nsHb1 has not yet been measured. Here we report electron self-exchange rate constants for nsHb1 and Mb as a test of their role in hydroxylamine reduction. These proteins are not suitable for analysis by NMR ZZ exchange, so a method was developed that uses cross-reactions between each hemoglobin and its deutero-hemin substituted counterpart. The resulting electron transfer is between identical proteins with low driving forces and thus closely approximates true electron self-exchange. The reactions can be monitored spectrally due to the distinct spectra of the prosthetic groups, and from this electron self-exchange rate constants of 880 (SynHb), 2,900 (nsHb1), and 0.05M−1 s−1 (Mb) have been measured for each hemoglobin. Calculations of cross-reactions using these values accurately predict hydroxylamine reduction rates for each protein, suggesting that electron self-exchange plays an important role in the reaction.
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      PubDate: 2015-06-19T15:48:49Z
       
  • Thermodynamics of Binding of a Sulfonamide Inhibitor to Metal-Mutated
           Carbonic Anhydrase as Studied by Affinity Capillary Electrophoresis
    • Abstract: Publication date: Available online 17 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Yosuke Sato , Hitoshi Hoshino , Nobuhiko Iki
      By affinity capillary electrophoresis (ACE), the thermodynamic binding constants of a sulfonamide (SA) inhibitor to bovine carbonic anhydrase II (CA) and metal mutated variants (M-CAs) were evaluated. 1-(4-Aminosulfonylphenylazo)-2-naphthol-6,8-disulfonate was used as the SA in the electrophoretic buffer for ACE. The Scatchard analysis of the dependence of the electrophoretic mobility of native CA on the SA concentration provided the binding constant to be K b =(2.29±0.05)×106 M−1 (at pH8.4, 25°C). On the other hand, apoCA showed far smaller value (K b =[3.76±0.14]×102 M−1), suggesting that the coordination of SA to the ZnII center controlled the binding thermodynamics. ACE of M-CAs showed the same behaviors as native CA but with different K b values. For example, Co-CA adopting the same tetrahedral coordination geometry as native CA exhibited the largest K b value ([2.55±0.05]×106 M−1) among the M-CAs. In contrast, Mn- and Ni-CA, which adopted the octahedral coordination geometry, had K b values that were about two orders of magnitude lower. Because the hydrophobic cavity of CA around the active center pre-organized the orientation of SA, thereby fixing the ligating NH− moiety to the apex of the tetrahedron supported by three basal His3 of CA, metals such as Zn and Co at the center of M-CA gave the most stable CA-SA complex. However, pre-organization was not favored for octahedral geometry. Thus, pre-organization of SA was the key to facilitating the tetrahedral coordination geometry of the ZnII active center of CA.
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      PubDate: 2015-06-19T15:48:49Z
       
  • A molecular level mechanism for uranium (VI) toxicity through Ca2+
           displacement in pyrroloquinoline quinone-dependent bacterial dehydrogenase
           
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Katherine A. Burbank , Robert A. Walker , Brent M. Peyton
      Dipicolinic acid (DPA), a small molecule analogue for the pyrroloquinoline quinone (PQQ) bacterial dehydrogenase cofactor, was used to model displacement of the complexing ion, Ca2+, by a uranium (VI) dioxo-cation, UO2 2+ . Complexation of UO2 2+ with DPA through the displacement of Ca2+ was examined with UV/visible spectroscopy, ESI (electrospray ionization)-Mass spectrometry, and density functional theory based-modeling. The UO2 2+ displacement of other biologically important metal cations (Zn2+, Cu2+, Ni2+, and Fe3+) from DPA was also examined. Results show that UO2 2+ has a distinctly higher binding affinity (logβ=10.2±0.1) for DPA compared to that of Ca2+ (logβ=4.6±0.1), and provide molecular level insight into the mechanism of uranium toxicity associated with the {ONO} site. These results support those of VanEngelen et al. (2011) where a key interaction between PQQ and UO2 2+ produced significant uranium toxicity in bacteria. The observed toxicity mechanism was determined to be the displacement of a Ca2+ cation bound to the {ONO} site on PQQ and was observed even at submicromolar UO2 2+ concentrations. Here we couple experimental findings with density functional theory (DFT) calculations to investigate the electronic and structural properties that make the {ONO} site so distinctively favorable for UO2 2+ binding. This novel approach using integrated experimental and fundamental atomic based models opens the path to identify a library of potential uranium interactions with critical biological molecules.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Editorial Board
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149




      PubDate: 2015-06-11T17:30:20Z
       
  • Contents
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149




      PubDate: 2015-06-11T17:30:20Z
       
  • Metals in the active site of native protein phosphatase-1
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Ewald Heroes , Jens Rip , Monique Beullens , Luc Van Meervelt , Stefan De Gendt , Mathieu Bollen
      Protein phosphatase-1 (PP1) is a major protein Ser/Thr phosphatase in eukaryotic cells. Its activity depends on two metal ions in the catalytic site, which were identified as manganese in the bacterially expressed phosphatase. However, the identity of the metal ions in native PP1 is unknown. In this study, total reflection X-ray fluorescence (TXRF) was used to detect iron and zinc in PP1 that was purified from rabbit skeletal muscle. Metal exchange experiments confirmed that the distinct substrate specificity of recombinant and native PP1 is determined by the nature of their associated metals. We also found that the iron level associated with native PP1 is decreased by incubation with inhibitor-2, consistent with a function of inhibitor-2 as a PP1 chaperone.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Copper(II) complexes with the non-steroidal anti-inflammatory drug
           tolfenamic acid: Structure and biological features
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Alketa Tarushi , Spyros Perontsis , Antonios G. Hatzidimitriou , Athanasios N. Papadopoulos , Dimitris P. Kessissoglou , George Psomas
      Copper(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid (Htolf) with the oxygen-donor ligands methanol (MeOH) or N,N-dimethylformamide (DMF) and/or the nitrogen-donor heterocyclic ligands 2,2′-bipyridine (bipy), 2,2′-bipyridylamine (bipyam), 1,10-phenanthroline (phen) or pyridine (py) were synthesized and characterized. The crystal structures of five novel complexes were determined by X-ray crystallography where tolfenamic acid is deprotonated being in different binding modes. Equimolar quantities of CuCl2, tolf−1 and bipy led to the formation of [Cu(tolf-O,O′)(bipy)Cl] (1), while with a 1:2 Cu(II):tolf ratio, complexes [Cu(tolf-O,O′)2(bipy)] (2), [Cu(tolf-O,O′)2(bipyam)]·0.5MeOH (3 0.5MeOH), [Cu(tolf-O,O′)(tolf-O)(phen)(MeOH)] (4) and [Cu(tolf-O)2(py)2(MeOH)2] (5) were isolated. The interaction of the complexes with serum albumin proteins was studied by fluorescence spectroscopy with the determined binding constant bearing relative high values. The scavenging ability of the complexes towards 1,1-diphenyl-picrylhydrazyl, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals was investigated and the in vitro inhibitory activity against soybean lipoxygenase was evaluated and complexes 4 and 5 were the more active compounds among those tested. Spectroscopic (UV), electrochemical (cyclic voltammetry) and physicochemical (viscosity measurements) techniques were employed in order to study the binding mode and strength of the complexes to calf-thymus (CT) DNA suggesting intercalation as the most possible mode of binding. Competitive studies with ethidium bromide (EB) revealed the ability of the complexes to displace the DNA-bound EB. The biological properties of complexes 1–5 were evaluated in regard to previously reported complex [Cu2(tolf-O,O′)4(DMF)2] (6).
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      PubDate: 2015-06-11T17:30:20Z
       
  • Synthesis, crystal structure and anaerobic DNA photocleavage of ruthenium
           complexes [Ru(tpy)(dpoq)Cl]+ and [Ru(tpy)(dpoq)CH3CN]2+
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Hui-juan Yu , Shu-mei Huang , Hui Chao , Liang-nian Ji
      Two new Ru(II) complexes [Ru(tpy)(dpoq)Cl]+ 1 and [Ru(tpy)(dpoq)CH3CN]2+ 2 (tpy=2,2':6',2''-terpyridine; dpoq=dipyrido[1,2,5]oxadiazolo[3,4-b]quinoxaline) have been synthesized and characterized by elemental analysis, 1H NMR, electrospray ionization mass spectra (ESI-MS) and X-ray crystallographic study. The experimental results of spectra titration, thermal denaturation and viscosity measurements suggest that the two complexes intercalatively bind to DNA. When irradiated under light, the two complexes could efficiently photocleave DNA both under aerobic and anaerobic condition. The mechanism studies reveal that the photocleavage reaction functions through both oxygen-independent (photoinduced electron transfer, type III reaction) and oxygen-dependent (singlet oxygen generation, type II reaction) pathways and the oxygen-independent pathway is the major process. These complexes will be more promising photodynamic therapy (PDT) candidates used for treating hypoxic tumors.
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      PubDate: 2015-06-11T17:30:20Z
       
  • A novel resting form of the trinuclear copper center in the double mutant
           of a multicopper oxidase, CueO, Cys500Ser/Glu506Ala
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Takao Kajikawa , Ryosuke Sugiyama , Kunishige Kataoka , Takeshi Sakurai
      A multicopper oxidase, CueO was doubly mutated at its type I copper ligand, Cys500 and an acidic amino acid residue located in the proton transfer pathway, Glu506, to Ser and Ala, respectively. Cys500Ser/Glu506Ala was mainly in a novel resting form to afford the absorption band at ca. 400nm and an EPR signal with a highly anisotropic character derived from type III copper. However, Cys500Ser/Glu506Ala gave the same reaction intermediate (peroxide intermediate) as that from Cys500Ser and Cys500Ser/Glu506Gln.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Cis-[RuCl(BzCN)(N–N)(P–P)]PF6 complexes: Synthesis and in
           vitro antitumor activity (BzCN=benzonitrile;
           N–N=2,2′-bipyridine; 1,10-phenanthroline;
           P–P=1,4-bis(diphenylphosphino) butane,
           1,2-bis(diphenylphosphino)ethane, or
           1,1′-(diphenylphosphino)ferrocene)
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Flávia de C. Pereira , Benedicto A.V. Lima , Aliny P. de Lima , Wanessa C. Pires , Thallita Monteiro , Lorena F. Magalhães , Wanderson Costa , Angélica E. Graminha , Alzir A. Batista , Javier Ellena , Elisângela de P. Siveira-Lacerda
      The motivation to use ruthenium complexes in cancer treatment has led our research group to synthesize complexes with this metal and test them against several types of tumor cells, yielding promising results. In this paper the results of biological tests, assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, were carried out on the complexes cis-[RuCl(BzCN)(bipy)(dppe)]PF6 (1), cis-[RuCl(BzCN)(bipy)(dppb)]PF6 (2), cis-[RuCl(BzCN)(bipy)(dppf)]PF6 (3) and cis-[RuCl(BzCN)(phen)(dppb)]PF6 (4) which are described [BzCN=benzonitrile; bipy=2,2′-bipyridine; phen=1,10-phenanthroline; dppe=1,2-bis(diphenylphosphino) ethane; dppb=1,4-bis-(diphenylphosphino)butane; dppf=1,1′-bis(diphenylphosphino)ferrocene]. The present study is focused on the cytotoxic activity of complexes (1)–(4) against four tumor cell lines and on the apoptosis and changes in the cell cycle and gene expression observed in the sarcoma 180 (S180) tumor cell line treated with complex (1). The results demonstrated that this complex inhibits S180 cell growth, with an IC50 of 17.02±8.21μM, while exhibiting lower cytotoxicity (IC50 =53.73±5.71μM) towards lymphocytes (normal cells). Flow cytometry revealed that the complex inhibits the growth of tumor cells by inducing apoptosis as evidenced by an increase in the proportion of cells positive for annexin V staining and G0/G1 phase cell-cycle arrest. Further investigation showed that complex (1) induces a drop in the mitochondrial membrane potential and provokes a decrease in Bcl-2 protein expression and increase in caspase 3 activation, while the increased activation of caspase 8 caused a decrease in the gene expression in caspases 3 and 9. Increases in Tp53 and Bax expressions were also observed.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Reactions of model proteins with aurothiomalate, a clinically established
           gold(I) drug: The comparison with auranofin
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Farivash Darabi , Tiziano Marzo , Lara Massai , Federica Scaletti , Elena Michelucci , Luigi Messori
      Aurothiomalate (AuTm) is an old, clinically established, antiarthritic gold drug that is currently being reconsidered as a candidate drug for cancer treatment and for other therapeutic indications within a more general drug repositioning program. As the biological effects of gold drugs seem to be mediated, mainly, by their interactions with protein targets we have analyzed here, in detail, the metalation patterns produced by aurothiomalate in a few model proteins. In particular, the reactions of aurothiomalate with the small proteins ribonuclease A, cytochrome c and lysozyme were explored through ESI MS (electrospray ionization mass spectrometry) analysis. Notably, characteristic and rather constant features emerged in the protein metalation patterns induced by AuTm that are markedly distinct from those caused by auranofin; a non-covalent interaction mode is invoked for AuTm binding to the mentioned proteins. The affinity constants of AuTm toward the three mentioned proteins were also initially assessed. The implications of the present findings are discussed.
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      PubDate: 2015-06-11T17:30:20Z
       
  • HSA-based phosphorescent probe for two-photon in vitro visualization
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Pavel S. Chelushkin , Natalia V. Nukolova , Alexei S. Melnikov , Pavel Yu. Serdobintsev , Pavel A. Melnikov , Dmitry V. Krupenya , Igor O. Koshevoy , Sergey V. Burov , Sergey P. Tunik
      Two-photon microscopy reveals several advantages over conventional one since it provides higher spatial resolution as well as deeper penetration into the sample under study. The development of suitable two-photon probes is one of the most challenging tasks in this area. Here we present phosphorescent non-covalent adduct of human serum albumin and Au-Ag alkynyl-diphosphine complex, [Au14Ag4(C2Ph)12(PPh2C6H4PPh2)6][PF6]4, which exhibits high cross section of two-photon-induced luminescence (δ TPE) within large near-infrared excitation wavelength region (700–800nm) with maximum δ TPE about 38 GM at 740nm. This feature makes it a promising probe for multiphoton bioimaging as demonstrated by successful visualization of glioma C6 cells and various tissues by two-photon confocal microscopy both in planar and z-stacking modes. Additionally, the broad excitation region enables optimization of the signal-to-background auto-fluorescence ratio via variation of excitation wavelength.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Solution structures of chloroquine-ferriheme complexes modeled using MD
           simulation and investigated by EXAFS spectroscopy
    • Abstract: Publication date: Available online 11 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): David Kuter , Victor Streltsov , Natalia Davydova , Gerhard A. Venter , Kevin J. Naidoo , Timothy J. Egan
      The interaction of chloroquine (CQ) and the μ-oxo dimer of iron(III) protoporphyrin IX (ferriheme) in aqueous solution was modeled using molecular dynamics (MD) simulations. Two models of the CQ-(μ-oxo ferriheme) complex were investigated, one involving CQ π-stacked with an unligated porphyrin face of μ-oxo ferriheme and the other in which CQ was docked between the two porphyrin rings. The feasibility of both models was tested by fitting computed structures to the experimental extended X-ray absorption fine structure (EXAFS) spectrum of the CQ-(μ-oxo ferriheme) complex in frozen aqueous solution. The docked model produced better agreement with experimental data, suggesting that this is the more likely structure in aqueous solution. The EXAFS fit indicated a longer than expected Fe-O bond of 1.87Å, accounting for the higher than expected magnetic moment of the complex. As a consequence, the asymmetric Fe-O-Fe stretch shifts much lower in frequency and was identified in the precipitated solid at 744cm−1 with the aid of the O18 isomer shift. Three important CQ-ferriheme interactions were identified in the docked structure. These were a hydrogen bond between the oxide bridge of μ-oxo ferriheme and the protonated quinolinium nitrogen atom of CQ; π-stacking between the quinoline ring of CQ and the porphyrin rings; and a close contact between the 7-chloro substituent of CQ and the porphyrin methyl hydrogen atoms. These interactions can be used to rationalize previously observed structure-activity relationships for quinoline-ferriheme association.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Recent advances on antimony(III/V) compounds with potential activity
           against tumor cells
    • Abstract: Publication date: Available online 10 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): S.K. Hadjikakou , I.I. Ozturk , C.N. Banti , N. Kourkoumelis , N. Hadjiliadis
      Antimony one of the heavier pnictogens, has been in medical use against microbes and parasites as well. Antimony-based drugs have been prescribed against leishmaniasis since the parasitic transmission of the tropical disease was understood in the beginning of the 20th century. The activity of arsenic against visceral leishmaniasis led to the synthesis of an array of arsenic-containing parasitic agents, among them the less toxic pentavalent antimonials: Stibosan, Neostibosan, and Ureastibamine. Other antimony drugs followed: sodium stibogluconate (Pentostam) and melglumine antimoniate (Glucantim or Glucantime); both continue to be in use today despite their toxic side effects and increasing loss in potency due to the growing resistance of the parasite against antimony. Antimony compounds and their therapeutic potentials are under consideration from many research groups, while a number of early reviews recording advances of antimony biomedical applications are also available. However, there are only few reports on the screening for antitumor potential of antimony compounds. This review focuses upon results obtained on the anti-proliferative activity of antimony compounds in the past years. This survey shows that antimony(III/V) complexes containing various type of ligands such as thiones, thiosemicarbazones, dithiocarbamates, carboxylic acids, or ketones, nitrogen donor ligands, exhibit selectivity against a variety of cancer cells. The role of the ligand type of the complex is elucidated within this review. The complexes and their biological activity are already reported elsewhere. However quantitative structure-activity relationship (QSAR) modeling studies have been carried out and they are reported for the first time here.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Copper(II) Complexation of Tacrine Hybrids with Potential
           Anti-Neurodegenerative Roles
    • Abstract: Publication date: Available online 10 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Catarina Quintanova , Rangappa S. Keri , Sílvia Chaves , M. Amélia Santos
      The complexity and multifactorial nature of neurodegenerative diseases turn quite difficult the development of adequate drugs for their treatment. Multi-target analogues, in conjugation with natural moieties, have been developed in order to combine acetylcholinesterase (AChE) inhibition with antioxidant properties, metal-binding capacity and inhibition of amyloid-β (Aβ) aggregation. Due to the recent interest on natural-based drugs and also the importance of studying the role of transition metal ions in the disease process, we herein evaluate the copper chelating capacity and inhibitory ability for self- and Cu-induced Aβ1–42 aggregation of two nature-base hybrid model compounds obtained from conjugation of a tacrine moiety with a S-allylcystein (1) or S-propargylcystein (2) moiety. Both compounds show a moderate chelating power towards Cu(II) (pCu 7.13-7.51, C L/C Cu =10, C Cu =10−6 M, pH7.4), with predominant formation of 1:1 complex species (CuL, CuH−1 L) for which the coordination sphere involves the N-amide and the NH2 amine of the cysteine derivative as well as the NH of tacrine. The compounds are able to improve the inhibition of Aβ aggregation in the presence of Cu(II) and this is slightly more relevant for the allyl derivative (1), a stronger copper chelator, than for the propargyl (2). Moreover, the presence of a chloro atom in the tacrine moiety and the size of the chain length between the two NH groups appeared also to improve the inhibition capacity for Aβ aggregation.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Antitumor and antiparasitic activity of novel ruthenium compounds with
           polycyclic aromatic ligands
    • Abstract: Publication date: Available online 9 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Helena Guiset Miserachs , Micaella Cipriani , Jordi Grau , Marta Vilaseca , Julia Lorenzo , Andrea Medeiros , Marcelo A. Comini , Dinorah Gambino , Lucía Otero , Virtudes Moreno
      Five novel ruthenium(II)–arene complexes with polycyclic aromatic ligands were synthesized, comprising three compounds of the formula [RuCl(η6-p-cym)(L)][PF6], where p-cym=1-isopropyl-4-methylbenzene and L are the bidentate aromatic ligands 1,10-phenanthroline-5,6-dione, 1, 5-amine-1,10-phenanthroline, 4, or 5,6-epoxy-5,6-dihydro- phenanthroline, 5. In the other two complexes, [RuCl2(η6-p-cym)(L')], the metal is coordinated to a monodentate ligand L', where L' is phenanthridine, 2, or 9-carbonilanthracene, 3. All compounds were fully characterized by mass spectrometry and elemental analysis, as well as NMR and IR spectroscopic techniques. Obtained ruthenium compounds as well as their respective ligands were tested for their antiparasitic and antitumoral activities. Even though all compounds showed lower T. brucei activity than the free ligands, they also resulted less toxic on mammalian cells. Cytotoxicity assays on HL60 cells showed a moderate antitumoral activity for all ruthenium compounds. Compound 1 was the most potent antitumoral (IC50 =1.26±0.78μM) and antiparasitic (IC50 =0.19μM) agent, showing high selectivity towards the parasites (selectivity index>100). As complex 1 was the most promising antitumoral compound, its interaction with ubiquitin as potential target was also studied. In addition, obtained ruthenium compounds were found to bind DNA, and they are thought to interact with this macromolecule mainly through intercalation of the aromatic ligand.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Molecular mechanisms of apoptosis and cell selectivity of zinc
           dithiocarbamates functionalized with hydroxyethyl substituents
    • Abstract: Publication date: Available online 9 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Yee Seng Tan , Kah Kooi Ooi , Kok Pian Ang , Abdah Md Akim , Yoke-Kqueen Cheah , Siti Nadiah Abdul Halim , Hoi-Ling Seng , Edward R.T. Tiekink
      In the solid state each of three binuclear zinc dithiocarbamates bearing hydroxyethyl groups, {Zn[S2CN(R)CH2CH2OH]2}2 for R=iPr (1), CH2CH2OH (2), and Me (3), and an all alkyl species, [Zn(S2CNEt2)2]2 (4), features a centrosymmetric {ZnSCS}2 core with a step topology; both 1 and 3 were isolated as monohydrates. All compounds were broadly cytotoxic, specifically against human cancer cell lines compared with normal cells, with greater potency than cisplatin. Notably, some selectivity was indicated with 2 being most potent against human ovarian carcinoma cells (cisA2780), and 4 being more cytotoxic toward multidrug resistant human breast carcinoma cells (MCF-7R), human colon adenocarcinoma cells (HT-29), and human lung adenocarcinoma epithelial cells (A549). Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis in HT-29 cells is demonstrated via both extrinsic and intrinsic pathways. Compounds 2–4 activate the p53 gene while 1 activates both p53 and p73. Cell cycle arrest at the S and G2/M phases correlates with inhibition of HT-29 cell growth. Cell invasion is also inhibited by 1–4 which is correlated with down-regulation of NF-ĸB.
      Graphical abstract image

      PubDate: 2015-06-11T17:30:20Z
       
  • Sol–gel Encapsulation of Binary Zn(II) Compounds in Silica
           Nanoparticles. Structure-Activity Correlations in Hybrid Materials
           Targeting Zn(II) Antibacterial Use
    • Abstract: Publication date: Available online 6 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): E. Halevas , C.M. Nday , E. Kaprara , V. Psycharis , C.P. Raptopoulou , G.E. Jackson , G. Litsardakis , A. Salifoglou
      In the emerging issue of enhanced multi-resistant properties in infectious pathogens, new nanomaterials with optimally efficient antibacterial activity and lower toxicity than other species attract considerable research interest. In an effort to develop such efficient antibacterials, we a) synthesized acid-catalyzed silica-gel matrices, b) evaluated the suitability of these matrices as potential carrier materials for controlled release of ZnSO4 and a new Zn(II) binary complex with a suitably designed well-defined Schiff base, and c) investigated structural and textural properties of the nanomaterials. Physicochemical characterization of the (empty-loaded) silica-nanoparticles led to an optimized material configuration linked to the delivery of the encapsulated antibacterial zinc load. Entrapment and drug release studies showed the competence of hybrid nanoparticles with respect to the a) zinc loading capacity, b) congruence with zinc physicochemical attributes, and c) release profile of their zinc load. The material antimicrobial properties were demonstrated against Gram-positive (S. aureus, B. subtilis, B. cereus) and negative (E. coli, P. aeruginosa, X. campestris) bacteria using modified agar diffusion methods. ZnSO4 showed less extensive antimicrobial behavior compared to Zn(II)-Schiff, implying that its bound ligand enhances zinc antimicrobial properties. All zinc-loaded nanoparticles were less antimicrobially active than zinc compounds alone, as encapsulation controls their release, thereby attenuating their antimicrobial activity. To this end, as the amount of loaded zinc increases, the antimicrobial behavior of the nano-agent improves. Collectively, for the first time, sol–gel zinc-loaded silica-nanoparticles were shown to exhibit well-defined antimicrobial activity, justifying due attention to further development of antibacterial nanotechnology.
      Graphical abstract image

      PubDate: 2015-06-08T15:27:47Z
       
  • Synthesis, crystal structure and biological activity of two Mn complexes
           with 4-acyl pyrazolone derivatives
    • Abstract: Publication date: Available online 5 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Yue Li , Jing Zhao , Chuan-Chuan He , Li Zhang , Su-Rong Sun , Guan-Cheng Xu
      In order to study the biological activities of transitional metal complexes based on 4-acyl pyrazolone derivatives, two Mn complexes [Mn(HLa)(La)]·(CH3CN)1.5 ·H2O (1) and [Mn2(Lb)2(μ-EtO)2(EtOH)2] (2) (H2La =N-(1-phenyl-3-methyl-4-benzoyl-5-pyrazolone)-2- thiophenecarboxylic acid hydrazide, H2Lb =N-(1-phenyl-3-methyl-4-propenylidene-5-pyrazolone)- 2-thiophenecarboxylic acid hydrazide) have been synthesized and characterized. Single crystal X-ray diffraction analysis indicated that 1 is a mononuclear complex and 2 exhibits a dinuclear centrosymmetric structure. Binding of the complexes with Herring Sperm DNA (HS-DNA) were showed that complexes 1 and 2 could intercalate to DNA with quenching constant of 5.3×104 M−1 and 4.9×104 M−1, respectively. The interactions of the complexes with bovine serum albumin (BSA) indicated complexes 1 and 2 could quench the intrinsic fluorescence of BSA in a static quenching process. Further, the inhibitory effects of the complexes on the cell population growth of the human esophageal cancer Eca-109 cells and the cervical cancer HeLa cells were determined by MTT assay, which indicated that both 1 and 2 significantly inhibited the growth of Eca-109 and HeLa cells, the inhibitory activity of complex 1 is stronger than that of 2. We further observed that complex 1 inhibited the growth of HeLa cells through inducing the apoptosis and arresting cell cycle at S phase. Our results suggested that both complexes 1 and 2 have DNA- and protein-binding capacity and antitumor activity.
      Graphical abstract image

      PubDate: 2015-06-08T15:27:47Z
       
  • Synthesis, chemical characterization, computational studies and biological
           activity of new DNA methyltransferases (DNMTs) specific inhibitor.
           Epigenetic regulation as a new and potential approach to cancer therapy
    • Abstract: Publication date: Available online 5 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): C. Pellerito , O. Morana , F. Ferrante , G. Calvaruso , A. Notaro , S. Sabella , T. Fiore
      This work deals with the synthesis, the chemical characterization of dibutyltin(IV) complex of caffeic acid (Bu2Sn(IV)HCAF, caf1) and its cytotoxic action on tumor cells. The coordination environment at the tin center was investigated by FTIR, 119Sn{1H} cross polarization magic angle spinning, electrospray ionization mass spectroscopy in the solid state and UV–vis, fluorescence and 1H, 13C and 119Sn NMR spectroscopy in solution phases. Density functional theory study confirmed the proposed structures in solution phase and indicated the most probable stable conformation. The effects on viability of breast cancer MDA-MB231, colorectal cancer HCT116, hepatocellular carcinoma HepG2 and Chang liver cells, an immortalized non-tumor hepatic cell line, have been investigated. The effect of a variation in structure of caf1 found to lead to a change in the respective antiproliferative properties: caf1 induces loss of viability in HCT116, MDA-MB-231, HepG2; the complex shows only moderate effects in non-tumor Chang liver cells. caf1 exerts lower cytotoxic activity than Bu2SnCl2, suggesting that the binding with H3CAF modulates the marked cytotoxic activity exerted by Bu2SnCl2; caf1 displays a considerably more pronounced antitumoural effect towards cell lines than caffeic acid. It is known that caffeic acid can modulate DNA (cytosine-5)-methyltransferases 1 (DNMT1) mediated DNA methylation. In this paper we demonstrate that caf1 treatment was able to induce a time-dependent reduction of global DNA methylated status. This effect was also confirmed by a concomitant reduction DNMT1 expression level. The effect induced by caf1 was more evident not only respect to untreated cells but also compared to H3CAF treated cells.
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      PubDate: 2015-06-08T15:27:47Z
       
  • A versatile salicyl hydrazonic ligand and its metal complexes as antiviral
           agents
    • Abstract: Publication date: Available online 27 May 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): D. Rogolino , M. Carcelli , A. Bacchi , C. Compari , Laura Contardi , E. Fisicaro , A. Gatti , M. Sechi , A. Stevaert , L. Naesens
      Acylhydrazones are very versatile ligands and their coordination properties can be easily tuned, giving rise to metal complexes with different nuclearities. In the last few years, we have been looking for new pharmacophores able to coordinate simultaneously two metal ions, because many enzymes have two metal ions in the active site and their coordination can be a successful strategy to inhibit the activity of the metalloenzyme. As a part of this ongoing research, we synthesised the acylhydrazone H2L and its complexes with Mg(II), Mn(II), Co(II), Ni(II), Cu(II) and Zn(II). Their characterization, both in solution - also by means of potentiometric studies - and in the solid state, evidenced the ability of the o-vanillin hydrazone scaffold to give rise to different types of metal complexes, depending on the metal and the reaction conditions. Furthermore, we evaluated both the free ligand and its metal complexes in in vitro studies against a panel of diverse DNA- and RNA-viruses. In particular, the Mg(II), Mn(II), Ni(II) and Zn(II) complexes had EC50 values in the low micromolar range, with a pronounced activity against vaccinia virus.
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      PubDate: 2015-05-28T07:22:58Z
       
  • Cellular trafficking, accumulation and DNA platination of a series of
           cisplatin-based dicarboxylato Pt(IV) prodrugs
    • Abstract: Publication date: Available online 26 May 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Mauro Ravera , Elisabetta Gabano , Ilaria Zanellato , Ilaria Bonarrigo , Manuela Alessio , Fabio Arnesano , Angela Galliani , Giovanni Natile , Domenico Osella
      A series of Pt(IV) anticancer prodrug candidates, having the equatorial arrangement of cisplatin and bearing two aliphatic carboxylato axial ligands, has been investigated to prove the relationship between lipophilicity, cellular accumulation, DNA platination and antiproliferative activity on the cisplatin-sensitive A2780 ovarian cancer cell line. Unlike cisplatin, no facilitate influx/efflux mechanism appears to operate in the case of the Pt(IV) complexes under investigation, thus indicating that they enter by passive diffusion. While Pt(IV) complexes having lipophilicity comparable to that of cisplatin (negative values of log P o/w) exhibit a cellular accumulation similar to that of cisplatin, the most lipophilic complexes of the series show much higher cellular accumulation (stemming from enhanced passive diffusion), accompanied by greater DNA platination and cell growth inhibition. Even if the Pt(IV) complexes are removed from the culture medium in the recovery process, the level of DNA platination remains very high and persistent in time, indicating efficient storing of the complexes and poor detoxification efficiency.
      Graphical abstract image

      PubDate: 2015-05-28T07:22:58Z
       
  • Reactivity of dinuclear copper(II) complexes towards melanoma cells:
           correlation with its stability, tyrosinase mimicking and nuclease activity
           
    • Abstract: Publication date: Available online 19 May 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Cléia Justino Nunes , Beatriz Essenfelder Borges , Lia Sumie Nakao , Eugénie Peyroux , Renaud Hardré , Bruno Faure , Marius Réglier , Michel Giorgi , Marcela Bach Prieto , Carla Columbano Oliveira , Ana M. Da Costa Ferreira
      In this work, the influence of two new dinuclear copper(II) complexes in the viability of melanoma cells (B16F10 and TM1MNG3) was investigated, with the aim of verifying possible correlations between their cytotoxicity and their structure. One of the complexes had a polydentate dinucleating amine-imine ligand (complex 2), and the other a tridentate imine and a diamine-bridging ligand (complex 4). The analogous mononuclear copper(II) species (complexes 1 and 3, respectively) were also prepared for comparative studies. Crystal structure determination of complex 2 indicated a square-based pyramidal geometry around each copper, coordinated to three N atoms from the ligand and the remaining sites being occupied by either solvent molecules or counter-ions. Complex 4 has a tetragonal geometry. Interactions of these complexes with human albumin protein (HSA) allowed an estimation of their relative stabilities. Complementary studies of their reactivity towards DNA indicated that all of them are able of causing significant oxidative damage, with single and double strand cleavages, in the presence of hydrogen peroxide. However, nuclease activity of the dinuclear species were very similar and much higher than that of the corresponding mononuclear compounds. Although complex 2, with a more flexible structure, exhibits a much higher tyrosinase activity than complex 4, having a more rigid environment around the metal ion, both complexes showed comparable cytotoxicity towards melanoma cells. Corresponding mononuclear complexes showed to be remarkably less reactive as tyrosinase mimics as well as cytotoxic agents. Morever, the dinuclear complexes showed higher cytotoxicity towards more melanogenic cells. The obtained results indicated that the structure of these species is decisive for its activity towards the malignant tumor cells tested.
      Graphical abstract image

      PubDate: 2015-05-23T07:09:57Z
       
  • Reduced accumulation of platinum drugs is not observed in drug-resistant
           ovarian cancer cell lines derived from cisplatin-treated patients
    • Abstract: Publication date: Available online 14 May 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Marina Stukova , Matthew D. Hall , Samantha D. Tsotsoros , James P. Madigan , Nicholas P. Farrell , Michael M. Gottesman
      The resistance of ovarian cancer towards front-line chemotherapy, usually cisplatin or carboplatin in combination with paclitaxel or docetaxel, remains a major clinical challenge. Resistance to these agents has been largely studied using cell lines selected for resistance to agents in vitro. We examined a series of paired cell lines derived from patients with ovarian cancer prior to chemotherapy (PEO1, PEO4, PEO14 and PEA1), and following the acquisition of resistance to a platinum-based chemotherapy regimen (PEO6, PEO23 and PEA2, respectively). All resistant patient lines showed resistance to cisplatin (2-5-fold), but this did not correspond with lowered accumulation. No general cross-resistance was observed for oxaliplatin, paclitaxel or docetaxel, and paclitaxel accumulation was not affected. PEO1 cells carrying BRCA2 mutations were hypersensitive to the PARP inhibitors olaparib and velaparib, but all other cell lines expressing functional forms of BRCA2 were less sensitive. While reduced drug accumulation was not observed, we believe these pairs of lines are of use to researchers studying Pt drug resistance and experimental therapeutics against drug-resistant ovarian cancer.
      Graphical abstract image

      PubDate: 2015-05-18T17:32:13Z
       
  • Oxidovanadium(IV) Sulfate-induced Glucose Uptake in HepG2 Cells through
           IR/Akt Pathway and Hydroxyl Radicals
    • Abstract: Publication date: Available online 15 May 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Qian Zhao , Deliang Chen , Pingsheng Liu , Taotao Wei , Fang Zhang , Wenjun Ding
      The insulin-mimetic and anti-diabetic properties of vanadium and related compounds have been well documented both in vitro and in vivo. However, the molecular basis of the link between vanadium and the insulin signaling pathway in diabetes mellitus is not fully described. We investigated the effects of reactive oxygen species (ROS) induced by oxidovanadium(IV) sulfate (VOSO4) on glucose uptake and the insulin signaling pathway in human hepatoma cell line HepG2. Exposure of cells to VOSO4 (5-50 μM) resulted in an increase in glucose uptake, insulin receptor (IR) and protein kinase B (Akt) phosphorylation and intracellular ROS generation. Using Western blot, we found that catalase and sodium formate, but not superoxide dismutase, prevented the increase of hydroxyl radical (·OH) generation and significantly decreased VOSO4-induced IR and Akt phosphorylation. These results suggest that VOSO4-induced ·OH radical, which is a signaling species, promotes glucose uptake via the IR/Akt signaling pathway.
      Graphical abstract image

      PubDate: 2015-05-18T17:32:13Z
       
  • Synthesis, crystal structure and investigation of mononuclear copper(II)
           and zinc(II) complexes of a new carboxylate rich tripodal ligand and their
           interaction with carbohydrates in alkaline aqueous solution
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Christopher D. Stewart , Mayra Pedraza , Hadi Arman , Hua-Jun Fan , Eduardo Luiz Schilling , Bruno Szpoganicz , Ghezai T. Musie
      A new carboxylate rich asymmetric tripodal ligand, N-[2-carboxybenzomethyl]-N-[carboxymethyl]-β-alanine (H3camb), and its di-copper(II), (NH4)2[1]2, and di-zinc(II), ((CH3)4 N)2[2]2, complexes have been synthesized as carbohydrate binding models in aqueous solutions. The ligand and complexes have been fully characterized using several techniques, including single crystal X-ray diffraction. The interactions of (NH4)2[1]2 and ((CH3)4 N)2[2]2 with d-glucose, d-mannose, d-xylose and xylitol in aqueous alkaline media were investigated using UV–Vis and 13C-NMR spectroscopic techniques, respectively. The molar conductance, NMR and ESI–MS studies indicate that the complexes dissociate in solution to produce the respective complex anions, 1 − and 2 −. Complexes 1 − and 2 − showed chelating ability towards the naturally abundant and biologically relevant sugars, d-glucose, d-mannose, d-xylose, and xylitol. The complex ions bind to one molar equivalent of the sugars, even in the presence of stoichiometric excess of the substrates, in solution. Experimentally obtained spectroscopic data and computational results suggest that the substrates bind to the metal center in a bidentate fashion. Apparent binding constant values, pK app, between the complexes and the substrates were determined and a specific mode of substrate binding is proposed. The pK app and relativistic density functional theory (DFT) calculated Gibbs free energy values indicate that d-mannose displayed the strongest interaction with the complexes. Syntheses, characterizations, detailed substrate binding studies using spectroscopic techniques, single crystal X-ray diffraction and geometry optimizations of the complex-substrates with DFT calculations are also reported.
      Graphical abstract image

      PubDate: 2015-05-18T17:32:13Z
       
  • Insights into the mechanisms underlying the antitumor activity of an
           oxidovanadium(IV) compound with the antioxidant naringenin. Albumin
           binding studies
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): María S. Islas , Luciana G. Naso , Luis Lezama , María Valcarcel , Clarisa Salado , Meritxell Roura-Ferrer , Evelina G. Ferrer , Patricia A.M. Williams
      Naringenin, a natural antioxidant present in grapefruit, oranges and the skin of tomatoes showed low antioxidant properties among other flavonoids due to its structural characteristics. Since many flavonoids were shown to have cell-killing and antioxidant activities, naringenin was investigated herein. In parallel with its antioxidant activities the flavonoid showed very low cytotoxicity at concentrations up to 100μM against lung (A549) and breast (SKBr3 and MDAMB231) cancer cell lines. Furthermore, a newly-synthesized and characterized complex of naringenin and oxidovanadium(IV) ([VIVO(nar)2]·2H2O, VOnar, with weak ferromagnetic coupling) was also studied. As a result, VOnar acted as a better compound on cell-killing and antioxidant activities (in vitro) than naringenin. The anti-proliferative effect of VOnar was accompanied by reactive oxygen species (ROS) generation, cell membrane and DNA damages, cell cycle arrest, caspase 3/7 activation and mitochondrial potential reduction. The higher parameters observed for the MDAMB231 cell line have been related to its low glutathione (GSH) content. The assays of the interaction of bovine serum albumin (BSA) with the complex showed the affinity of protein toward it and that there is only one binding site on the BSA molecule. However, metal complexation decreased the binding affinity to BSA of naringenin probably due to a steric hindrance of the complex.
      Graphical abstract image

      PubDate: 2015-05-18T17:32:13Z
       
  • Inhibitory effects of nitrite on the reactions of bovine carbonic
           anhydrase II with CO2 and bicarbonate consistent with zinc-bound nitrite
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Per M. Nielsen , Angela Fago
      Carbonic anhydrase (CA) is a zinc enzyme that catalyzes hydration of carbon dioxide (CO2) and dehydration of bicarbonate in red blood cells, thus facilitating CO2 transport and excretion. Bovine CA II may also react with nitrite to generate nitric oxide, although nitrite is a known inhibitor of the CO2 hydration reaction. To address the potential in vivo interference of these reactions and the nature of nitrite binding to the enzyme, we here investigate the inhibitory effect of 10–30mM nitrite on Michaelis–Menten kinetics of CO2 hydration and bicarbonate dehydration by stopped-flow spectroscopy. Our data show that nitrite significantly affects the apparent dissociation constant K M for CO2 (11mM) and bicarbonate (221mM), and the turnover number k cat for the CO2 hydration (1.467×106 s−1) but not for the bicarbonate dehydration (7.927×105 s−1). These effects demonstrate mixed and competitive inhibition for the reaction with CO2 and bicarbonate, respectively, and are consistent with nitrite binding to the active site zinc. The high apparent dissociation constant found here for CO2, bicarbonate and nitrite (16–120mM) are all overall consistent with published data and reveal a large capacity of free enzyme available for binding each of the three substrates at their in vivo levels, with little or no significant interference among reactions. The low affinity of the enzyme for nitrite suggests that the in vivo interaction between red blood cell CA II and nitrite requires compartmentalization at the anion exchanger protein of the red cell membrane to be physiologically relevant.
      Graphical abstract image

      PubDate: 2015-05-18T17:32:13Z
       
 
 
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