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  Subjects -> CHEMISTRY (Total: 767 journals)
    - ANALYTICAL CHEMISTRY (45 journals)
    - CHEMISTRY (531 journals)
    - CRYSTALLOGRAPHY (22 journals)
    - ELECTROCHEMISTRY (25 journals)
    - INORGANIC CHEMISTRY (40 journals)
    - ORGANIC CHEMISTRY (40 journals)
    - PHYSICAL CHEMISTRY (64 journals)

INORGANIC CHEMISTRY (40 journals)

Acta Polymerica     Hybrid Journal   (Followers: 6)
Additives for Polymers     Full-text available via subscription   (Followers: 18)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 4)
Advances in Polymer Technology     Hybrid Journal   (Followers: 10)
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: 5)
European Polymer Journal     Hybrid Journal   (Followers: 41)
Heterocyclic Communications     Full-text available via subscription   (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: 18)
Inorganic Chemistry Communications     Hybrid Journal   (Followers: 7)
Inorganic Chemistry Frontiers     Full-text available via subscription  
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: 2)
Journal of Inorganic and Organometallic Polymers and Materials     Partially Free   (Followers: 6)
Journal of Inorganic Biochemistry     Hybrid Journal   (Followers: 3)
Journal of Inorganic Chemistry     Open Access  
Journal of Polymer Engineering     Full-text available via subscription   (Followers: 7)
Journal of Polymers and the Environment     Hybrid Journal   (Followers: 3)
Journal of Separation Science     Hybrid Journal   (Followers: 6)
Open Journal of Inorganic Chemistry     Open Access   (Followers: 1)
Plasmas and Polymers     Hybrid Journal  
Polymer Bulletin     Hybrid Journal   (Followers: 7)
Polymer Composites     Hybrid Journal   (Followers: 8)
Polyoxometalate Chemistry     Open Access  
Reviews in Inorganic Chemistry     Full-text available via subscription  
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
   [5 followers]  Follow    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
     ISSN (Print) 0162-0134
     Published by Elsevier Homepage  [2563 journals]   [SJR: 0.807]   [H-I: 79]
  • Fluoroquinolone–metal complexes: A route to counteract bacterial
           resistance?
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138
      Author(s): Maria J. Feio , Isabel Sousa , Mariana Ferreira , Luís Cunha-Silva , Raúl G. Saraiva , Carla Queirós , José G. Alexandre , Vasco Claro , Adélia Mendes , Rosa Ortiz , Sandra Lopes , Ana Luísa Amaral , João Lino , Patrícia Fernandes , Ana João Silva , Lisete Moutinho , Baltazar de Castro , Eulália Pereira , Lourdes Perelló , Paula Gameiro
      Microbial resistance to antibiotics is one of the biggest public health threats of the modern world. Antibiotic resistance is an area of much clinical relevance and therefore research that has the potential to identify agents that may circumvent it or treat resistant infections is paramount. Solution behavior of various fluoroquinolone (FQ) complexes with copper(II) in the presence and absence of 1,10-phenanthroline (phen) was studied in aqueous solution, by potentiometry and/or spectrophotometry, and are herein described. The results obtained showed that under physiological conditions (micromolar concentration range and pH7.4) only copper(II):FQ:phen ternary complexes are stable. Hence, these complexes were synthesised and characterised by means of UV–visible and IR spectroscopy, elemental analysis and single-crystal X-ray diffraction. In these complexes, the FQ acts as a bidentate ligand that coordinates the metal cation through the carbonyl and carboxyl oxygen atoms and phen coordinates through two N-atoms forming the equatorial plane of a distorted square-pyramidal geometry. The fifth position of the penta-coordinated Cu(II) centre is generally occupied axially by an oxygen atom from a water molecule or from a nitrate ion. Minimum inhibitory concentration (MIC) determinations of the complexes and comparison with free FQ in various E. coli strains indicate that the Cu-complexes are as efficient antimicrobials as the free antibiotic. Moreover, results strongly suggest that the cell intake route of both species is different supporting, therefore, the complexes' suitability as candidates for further biological testing in FQ-resistant microorganisms.
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      PubDate: 2014-07-27T22:37:22Z
       
  • Structural diversity of polyoxomolybdate clusters along the three-fold
           axis of the molybdenum storage protein
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138
      Author(s): Juliane Poppe , Eberhard Warkentin , Ulrike Demmer , Björn Kowalewski , Thomas Dierks , Klaus Schneider , Ulrich Ermler
      The molybdenum storage protein (MoSto) can store more than 100 Mo or W atoms as discrete polyoxometalate (POM) clusters. Here, we describe the three POM cluster sites along the threefold axis of the protein complex based on four X-ray structures with slightly different polyoxomolybdate compositions between 1.35 and 2Å resolution. In contrast to the Moα-out binding site occupied by an Mo3 cluster, the Moα-in and Moβ binding sites contain rather weak and non-uniform electron density for the Mo atoms (but clearly identifiable by anomalous data), suggesting the presence of POM cluster ensembles and/or degradation products of larger aggregates. The “Moα-in cluster ensemble” was interpreted as an antiprism-like Mo6 species superimposed with an Mo7 pyramide and the “Moβ cluster ensemble” as an Mo13 cluster (present mostly in a degraded form) composed of a pyramidal Mo7 and a Mo3 building block linked by three spatially separated MoO x units. Inside the ball-shaped Mo13 cluster sits an occluded central atom, perhaps a metal ion. POM cluster formation at the Moα-in and Moβ sites appears to be driven by filtering out and binding/protecting self-assembled transient species complementary to the protein template.
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      PubDate: 2014-07-27T22:37:22Z
       
  • Silver carboxylate metal–organic frameworks with highly
           antibacterial activity and biocompatibility
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138
      Author(s): Xinyi Lu , Junwei Ye , Dekui Zhang , Ruixia Xie , Raji Feyisa Bogale , Yuan Sun , Limei Zhao , Qi Zhao , Guiling Ning
      Two novel Ag-based metal–organic frameworks (MOFs) [Ag2(O-IPA)(H2O)·(H3O)] (1) and [Ag5(PYDC)2(OH)] (2) were synthesized under the hydrothermal conditions using aromatic–carboxylic acids containing hydroxyl and pyridyl groups as ligands (HO-H2IPA=5-hydroxyisophthalic acid and H2PYDC=pyridine-3, 5-dicarboxylic acid). Single crystal X-ray diffraction indicated that two compounds exhibit three-dimensional frameworks constructed from different rod-shaped molecular building blocks. Both compounds favor slow release of Ag+ ions leading to excellent and long-term antimicrobial activities towards Gram-negative bacteria, Escherichia coli (E. coli) and Gram-positive bacteria, Staphylococcus aureus (S. aureus). Their antibacterial potency was evaluated by using a minimal inhibition concentration (MIC) benchmark and an inhibition zone testing. High-resolution transmission electron microscope images indicate that the Ag-based MOFs could rupture the bacterial membrane resulting in cell death. Hematological study showed that these MOFs exhibit good biocompatibility in mice. In addition, good thermal stability and optical stability under UV–visible and visible light are beneficial for their antibacterial application.
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      PubDate: 2014-07-27T22:37:22Z
       
  • Mono and dinuclear phosphinegold(I) sulfanylcarboxylates: Influence of
           nuclearity and substitution of PPh3 for PEt3 on cytotoxicity
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138
      Author(s): Elena Barreiro , José S. Casas , María D. Couce , Agustín Sánchez , Angeles Sánchez-Gonzalez , José Sordo , Ezequiel M. Vázquez-López
      Gold complexes of the type [Au(PEt3)(Hxspa)] were prepared by reacting triethylphosphinegold(I) chloride in ethanol/water (8:1) with the 3-(aryl)-2-sulfanylpropenoic acids H2 xspa [x =p=3-phenyl-; f=3-(2-furyl)-; t=3-(2-thienyl)-; py=3-(2-pyridyl); Clp=3-(2-Chlorophenyl)-; -o-mp=3-(2-methoxyphenyl)-; -p-mp=3-(4-methoxyphenyl)-; -o-hp=3-(2-hydroxyphenyl)-; -p-hp=3-(4-hydroxyphenyl)-; -diBr-o-hp=3-(3,5-dibromo-2-hidroxyphenyl-); spa=2-sulfanylpropenoato] or 2-cyclopentylidene-2-sulfanylacetic acid (H2cpa) and KOH in a 1:1:1 mole ratio. The compounds were characterized by IR spectroscopy and FAB mass spectrometry and by 1H, 13C and 31P NMR spectroscopy. The in vitro antitumor activity of these and of the previously described dinuclear [(AuPEt3)2(xspa)] complexes against the HeLa-229, A2780 and A2780cis cell lines was determined and compared with those of the analogous PPh3 complexes. The results show that the substitution of the PPh3 ligand by PEt3 is particularly effective in increasing the cytotoxicity of the dinuclear [(AuPR3)2(xspa)] complexes, giving rise to compounds that are significantly more active than cisplatin against the aforementioned cell lines. In addition, and as a preliminary test for nephrotoxicity, the cytotoxicity of the most active compounds against the normal renal LCC-PK1 cell line was evaluated and compared with that of cisplatin.
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      PubDate: 2014-07-27T22:37:22Z
       
  • Editorial Board
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138




      PubDate: 2014-07-27T22:37:22Z
       
  • Contents
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138




      PubDate: 2014-07-27T22:37:22Z
       
  • Auranofin and related heterometallic gold(I)–thiolates as potent
           inhibitors of methicillin-resistant Staphylococcus aureus bacterial
           strains
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138
      Author(s): Yozane Hokai , Boruch Jurkowicz , Jacob Fernández-Gallardo , Nuruddinkodja Zakirkhodjaev , Mercedes Sanaú , Theodore R. Muth , María Contel
      A series of new heterometallic gold(I) thiolates containing ferrocenyl-phoshines were synthesized. Their antimicrobial properties were studied and compared to that of FDA-approved drug, auranofin (Ridaura), prescribed for the treatment of rheumatoid arthritis. MIC in the order of one digit micromolar were found for most of the compounds against Gram-positive bacteria Staphylococcus aureus and CA MRSA strains US300 and US400. Remarkably, auranofin inhibited S. aureus, US300 and US400 in the order of 150–300nM. This is the first time that the potent inhibitory effect of auranofin on MRSA strains has been described. The effects of a selected heterometallic compound and auranofin were also studied in a non-tumorigenic human embryonic kidney cell line (HEK-293).
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      PubDate: 2014-07-27T22:37:22Z
       
  • Synthesis, structural characterization and cytotoxic activity of ternary
           copper(II)–dipeptide–phenanthroline complexes. A step towards
           the development of new copper compounds for the treatment of cancer
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Sebastián Iglesias , Natalia Alvarez , María H. Torre , Eduardo Kremer , Javier Ellena , Ronny R. Ribeiro , Rafael P. Barroso , Antonio J. Costa-Filho , M. Gabriela Kramer , Gianella Facchin
      In the search for new compounds with antitumor activity, coordination complexes with different metals are being studied by our group. This work presents the synthesis and characterization of six copper complexes with general stoichiometry [Cu(L-dipeptide)(phen)]·nH2O (were phen=1,10-phenanthroline) and their cytotoxic activities against tumor cell lines. To characterize these systems, analytical and spectroscopic studies were performed in solid state (by UV–visible, IR, X-ray diffraction) including the crystal structure of four new complexes (of the six complexes studied): [Cu(Ala-Phe)(phen)]·4H2O, [Cu(Phe-Ala)(phen)]·4H2O, [Cu(Phe-Val)(phen)]·4.5H2O and [Cu(Phe-Phe)(phen)]·3H2O. In all of them, the copper ion is situated in a distorted squared pyramidal environment. The phen ligand is perpendicular to the dipeptide, therefore exposed and potentially available for interaction with biological molecules. In addition, for all the studied complexes, structural information in solution using EPR and UV–visible spectroscopies were obtained, showing that the coordination observed in solid state is maintained. The lipophilicity, DNA binding and albumin interaction were also studied. Biological experiments showed that all the complexes induce cell death in the cell lines: HeLa (human cervical adenocarcinoma), MCF-7 (human metastatic breast adenocarcinoma) and A549 (human lung epithelial carcinoma). Among the six complexes, [Cu(Ala-Phe)(phen)] presents the lowest IC50 values. Taken together all these data we hypothesize that [Cu(Ala-Phe)(phen)] may be a good candidate for further studies in vivo.
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      PubDate: 2014-07-27T22:37:22Z
       
  • 8-Hydroxyquinoline Schiff-base compounds as antioxidants and modulators of
           copper-mediated Aβ peptide aggregation
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Luiza M.F. Gomes , Rafael P. Vieira , Michael R. Jones , Michael C.P. Wang , Christine Dyrager , Elaine M. Souza-Fagundes , Jeferson G. Da Silva , Tim Storr , Heloisa Beraldo
      One of the hallmarks of Alzheimer's disease (AD) in the brain are amyloid-β (Aβ) plaques, and metal ions such as copper(II) and zinc(II) have been shown to play a role in the aggregation and toxicity of the Aβ peptide, the major constituent of these extracellular aggregates. Metal binding agents can promote the disaggregation of Aβ plaques, and have shown promise as AD therapeutics. Herein, we describe the syntheses and characterization of an acetohydrazone (8-H2QH), a thiosemicarbazone (8-H2QT), and a semicarbazone (8-H2QS) derived from 8-hydroxyquinoline. The three compounds are shown to be neutral at pH7.4, and are potent antioxidants as measured by a Trolox Equivalent Antioxidant Capacity (TEAC) assay. The ligands form complexes with CuII, 8-H2QT in a 1:1 metal:ligand ratio, and 8-H2QH and 8-H2QS in a 1:2 metal:ligand ratio. A preliminary aggregation inhibition assay using the Aβ1–40 peptide showed that 8-H2QS and 8-H2QH inhibit peptide aggregation in the presence of CuII. Native gel electrophoresis/Western blot and TEM images were obtained to give a more detailed picture of the extent and pathways of Aβ aggregation using the more neurotoxic Aβ1−42 in the presence and absence of CuII, 8-H2QH, 8-H2QS and the drug candidate PBT2. An increase in the formation of oligomeric species is evident in the presence of CuII. However, in the presence of ligands and CuII, the results match those for the peptide alone, suggesting that the ligands function by sequestering CuII and limiting oligomer formation in this assay.
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      PubDate: 2014-07-27T22:37:22Z
       
  • Comparison of oxygen-induced radical intermediates in iNOS oxygenase
           domain with those from nNOS and eNOS
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Vladimír Berka , Wen Liu , Gang Wu , Ah-Lim Tsai
      Inducible nitric-oxide synthase (iNOS) produces the reactive oxygen and nitrogen species (ROS/RNS) involved in bacteria killing and is crucial in the host defense mechanism. However, high level ROS/RNS can also be detrimental to normal cells and thus their production has to be tightly controlled. Availability or deficiency of tetrahydrobiopterin (BH4) cofactor and l-arginine substrate controls coupling or uncoupling of NOS catalysis. Fully coupled reaction, with abundant BH4 and l-arginine, produces NO whereas the uncoupled NOS (in the absence of BH4 and/or l-arginine) generates ROS/RNS. In the current work we focus on direct rapid freeze EPR to characterize the structure and kinetics of oxygen-induced radical intermediates produced by ferrous inducible NOS oxygenase domain (iNOSox) in the presence or absence of BH4 and/or l-arginine. Fully reconstituted iNOSox (+BH4, +L-Arg) forms a dimer and yields a typical BH4 radical that indicates coupled reaction. iNOSox (−BH4) remains mainly monomeric and produces exclusively superoxide, that is only marginally affected by the presence of l-arginine. iNOSox (+BH4, −L-Arg) exists as a monomer/dimer mixture and yields both BH4 radical and superoxide. Present study is a natural extension of our previous work on the ferrous endothelial NOSox (eNOSox) [V. Berka, G. Wu, H.C. Yeh, G. Palmer, A.L. Tsai, J. Biol. Chem. 279 (2004) 32243–32251] and ferrous neuronal NOSox (nNOSox) [V. Berka, L.H. Wang, A.L. Tsai, Biochemistry 47 (2008) 405–420]. Overall, our data suggests different regulatory roles of l-arginine and BH4 in the production of oxygen-induced radical intermediates in NOS isoforms which nicely serve individual functional role.
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      PubDate: 2014-07-27T22:37:22Z
       
  • In vitro antibacterial activity of meclofenamate metal complexes with
           Cd(II), Pb(II), Co(II), and Cu(II). Crystal structures of
           [Cd(C14H10NO2Cl2)2∙(CH3OH)]n and [Cu(C14H10NO2Cl2)2(C5H5N)2]
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): T. Palacios-Hernández , H. Höpfl , J.L. Sánchez-Salas , E. González-Vergara , A. Pérez-Benítez , M.A. Quiroz-Alfaro , M.A. Méndez-Rojas
      The synthesis and characterization of five metal complexes derived from sodium meclofenamate (1) are reported: [Cd(C14H10NO2Cl2)2∙(CH3OH)]n∙nCH3OH (6), [Pb(C14H10NO2Cl2)2]n (7), [Co(C14H10NO2Cl2)]n (8), [Cu(C14H10NO2Cl2)]n (9), and [Cu(C14H10NO2Cl2)2(C5H5N)2] (10) (C14H10NO2Cl2 =meclofenamate; C5H5N=pyridine). The characterization of the compounds was based on FTIR and UV–visible spectroscopy, mass spectrometry and, in the case of complexes 6 and 10, single crystal X-ray diffraction analysis. For compound 6, the structural analysis revealed a 1-D polymeric chain structure, in which pentagonal planar [Cd(RCOO)2(CH3OH)] units were linked through bridging carboxylate functions of the meclofenamate ligands. The overall coordination environment of the Cd(II) ions was seven-coordinate, since each carboxylate group exhibited a μ3-bridging coordination mode. On the other hand, for complex 10 a discrete mononuclear structure was observed, in which the six-coordinate copper(II) metal atoms were coordinated by two pyridine molecules and the carboxylate functions of two meclofenamate entities, in an anisobidentate coordination mode. The antibacterial activity of compounds 6–9 against four strains of Gram positive (Staphylococcus aureus and Bacillus subtilis) and Gram negative (Escherichia coli and Pseudomonas aeruginosa) bacteria was examined, finding that only complex 6 was active. Additionally, it was found that the Co(II) and Cu(II) complexes 8 and 9 showed peroxidase activity.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • A monofunctional trinuclear platinum complex with steric hindrance
           demonstrates strong cytotoxicity against tumor cells
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Shangnong Wu , Xiaoyong Wang , Yafeng He , Zhenzhu Zhu , Chengcheng Zhu , Zijian Guo
      Polynuclear platinum complexes constitute a special class of hopeful antitumor agents. In this study, a Y-type monofunctional trinuclear platinum complex (MTPC) with 1,3,5-tris(pyridin-2-ylmethoxy)benzene, ammine and chloride as ligands was synthesized and characterized by 1H NMR and electrospray ionization mass spectrometry (ESI-MS). The DNA binding mode of MTPC was investigated using circular dichroism spectroscopy and gel electrophoresis, and the reactivity of MTPC towards glutathione was studied by 1H NMR and ESI-MS. The results show that MTPC can affect the conformation of calf-thymus DNA (CT-DNA) significantly and tends to form 1,4-GG rather than 1,2-GG intrastrand crosslinks, which are different from the instance of cisplatin. MTPC reacts with glutathione quite slowly in comparison with cisplatin because of the steric hindrance. The cytotoxicity of MTPC was tested on the human breast cancer cell line MCF-7, the human non-small-cell lung cancer cell line A549, and the human ovarian cancer cell line Skov-3 by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. MTPC is more potent than or comparable to cisplatin. The cellular inhibition mode of MTPC was examined by flow cytometry using MCF-7 cells. MTPC arrests the cell cycle mainly in G2 or M phase, while cisplatin arrests the cell cycle in S phase. Similar to cisplatin, MTPC kills the cells predominantly through an apoptotic pathway.
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      PubDate: 2014-07-27T22:37:22Z
       
  • Mn(II)/Mn(III) and Fe(III) binding capability of two Aspergillus fumigatus
           siderophores, desferricrocin and N′, N″,
           N‴-triacetylfusarinine C
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Etelka Farkas , Orsolya Szabó , Péter L. Parajdi-Losonczi , György Balla , István Pócsi
      Manganese(II) and manganese(III) complexes of the exocyclic desferricrocin (H3DFCR) and endocyclic triacetylfusarinine C (H3TAF) in solution have been studied by using pH-potentiometry, UV–Vis spectrophotometry, relaxometry and cyclic voltammetry. A comparison between the present results and the corresponding ones for the open-chain analogues, desferrioxamine B (DFB) and desferricoprogen (DFC), shows (i) The dissociation processes of H3DFCR occur in the expected pH-range (pH7–10.5), but hydrogen bonding is assumed to be responsible for a quite low proton dissociation constant (pK=4.18) of H3TAF and also an unusually high one (10.59). (ii) Moderate stability complexes with 1:1 Mn(II) to ligand ratio are formed with all four siderophores. (iii) The coordination of the three hydroxamates of a siderophore takes place in stepwise processes, except the case of desferricrocin, with which, large-extent overlapping of the processes occurs. (iv) Out of the four tris-chelated [ML] type complexes, the complex of DFCR is the most compact, as it is indicated by the relaxivity values. (v) Following the stoichiometric oxidation of the Mn(II)–siderophore complexes at pH≥9, tris-chelated Mn(III) complexes are formed. To make a comparison between the stability of the Mn(III) and the corresponding Fe(III) complexes of DFCR and TAF, the determination of the stability of the Fe(III) complexes under our condition has also been performed, by using UV–Vis spectrophotometry. Comparable stability of the corresponding complexes was found. (vi) Correlation study of the stability constants resulted in estimation of the constant of the Mn(III) monohydroxo complex, for which there was no data in the literature under our conditions.
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      PubDate: 2014-07-27T22:37:22Z
       
  • Mechanistic basis for the enantioselectivity of the anaerobic
           hydroxylation of alkylaromatic compounds by ethylbenzene dehydrogenase
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Maciej Szaleniec , Agnieszka Dudzik , Bartłomiej Kozik , Tomasz Borowski , Johann Heider , Małgorzata Witko
      The enantioselectivity of reactions catalyzed by ethylbenzene dehydrogenase, a molybdenum enzyme that catalyzes the oxygen-independent hydroxylation of many alkylaromatic and alkylheterocyclic compounds to secondary alcohols, was studied by chiral chromatography and theoretical modeling. Chromatographic analyses of 22 substrates revealed that this enzyme exhibits remarkably high reaction enantioselectivity toward (S)-secondary alcohols (18 substrates converted with >99% ee). Theoretical QM:MM modeling was used to elucidate the structure of the catalytically active form of the enzyme and to study the reaction mechanism and factors determining its high degree of enantioselectivity. This analysis showed that the enzyme imposes strong stereoselectivity on the reaction by discriminating the hydrogen atom abstracted from the substrate. Activation of the pro(S) hydrogen atom was calculated to be 500 times faster than of the pro(R) hydrogen atom. The actual hydroxylation step (i.e., hydroxyl group rebound reaction to a carbocation intermediate) does not appear to be enantioselective enough to explain the experimental data (the calculated rate ratios were in the range of only 2–50 for pro(S): pro(R)-oriented OH rebound).
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      PubDate: 2014-07-27T22:37:22Z
       
  • Cyclopalladated and cycloplatinated benzophenone imines: Antitumor,
           antibacterial and antioxidant activities, DNA interaction and cathepsin B
           inhibition
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Joan Albert , Lucía D'Andrea , Jaume Granell , Pepita Pla-Vilanova , Josefina Quirante , Muhammad Kaleem Khosa , Carme Calvis , Ramon Messeguer , Josefa Badía , Laura Baldomà , Mercè Font-Bardia , Teresa Calvet
      The antitumor, antibacterial and antioxidant activity, DNA interaction and cathepsin B inhibition of cyclo-ortho-palladated and -platinated compounds [Pd(C,N)]2(μ-X)2 [X=OAc (1), X=Cl (2)] and trans- N , P -[M(C,N)X(PPh3)] [M=Pd, X=OAc (3), M=Pd, X=Cl (4), M=Pt, X=Cl (5)] are discussed [(C,N)=cyclo-ortho-metallated benzophenone imine]. The cytotoxicity of compound 5 has been evaluated towards human breast (MDA-MB-231 and MCF-7) and colon (HCT-116) cancer cell lines and that of compounds 1–4 towards the HCT-116 human colon cancer cell line. These cytotoxicities have been compared with those previously reported for compounds 1–4 towards MDA-MB-231 and MCF-7 cancer cell lines. Compound 3 and 4 were approximately four times more active than cisplatin against the MDA-MB-231 and MCF-7 cancer cell lines, and compound 5, was approximately four times more potent than cisplatin against the HCT-116 cancer cell line. The antibacterial activity of compounds 1–5 was in between the ranges of activity of the commercial antibiotic compounds cefixime and roxithromycin. Complexes 1–2 and 4–5 presented also antioxidant activity. Compounds 1–5 alter the DNA tertiary structure in a similar way to cisplatin, but at higher concentration, and do not present a high efficiency as cathepsin B inhibitors. Compound 5 has not been previously described, and its preparation, characterization, and X-ray crystal structure are reported.
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      PubDate: 2014-07-27T22:37:22Z
       
  • Antitumor platinum(IV) derivatives of oxaliplatin with axial valproato
           ligands
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Vojtech Novohradsky , Lenka Zerzankova , Jana Stepankova , Oldrich Vrana , Raji Raveendran , Dan Gibson , Jana Kasparkova , Viktor Brabec
      We report new anticancer prodrugs, platinum(IV) derivatives of oxaliplatin conjugated with valproic acid (VPA), a well-known drug having histone deacetylase inhibitory activity. Like most platinum(IV) derivatives, the cytotoxicity of the conjugates was lower in cell culture than that of oxaliplatin, but greater than those of its Pt(IV) derivative containing biologically inactive axial ligands in several cancer cell lines. Notably, these conjugates display activity in both cisplatin sensitive- and resistant tumor cells capable of both markedly enhanced accumulation in tumor cells and acting in a dual threat manner, concurrently targeting histone deacetylase and genomic DNA. These results demonstrate the dual targeting strategy to be a valuable route to pursue in the design of platinum agents which may be more effective in cancer types that are typically resistant to therapy by conventional cisplatin. Moreover, platinum(IV) derivatives containing VPA axial ligands seem to be promising dual-targeting candidates for additional preclinical studies.
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      PubDate: 2014-07-27T22:37:22Z
       
  • Two structurally analogous ruthenium complexes as naked-eye and reversible
           molecular “light switch” for G-quadruplex DNA
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Xiao-Hui Lu , Shuo Shi , Jun-Liang Yao , Xing Gao , Hai-Liang Huang , Tian-Ming Yao
      A pair of symmetrical furyl based ruthenium(II) complexes ([Ru(phen)2dpq-df]2+ (1) and [Ru(bpy)2dpq-df]2+ (2) (phen=1,10-phenanthroline, bpy=2,2′-bipyridine, dpq-df=dipyrido (3,2-a:2′,3′-c) quinoxaline-difuran) have been prepared and characterized. The binding properties of both complexes toward G-quadruplex DNA have been investigated by fluorescence spectroscopy, UV–Vis spectroscopy, circular dichroism (CD), fluorescence resonance energy transfer (FRET) melting assays and molecular docking studies. The experimental results indicated that both Ru-complexes exhibited a remarkable “light switch” effect in the presence of hybrid G-quadruplex DNA. Interestingly, the “light switch” can be repeated off and on through the successive addition of Cu2+ ions and EDTA, and all these behaviors can be observed even by the naked eyes. Moreover, FRET melting assay revealed that both complexes could be potential stabilizers for G-quadruplex architectures. The computational studies not only confirmed that the two complex molecules bound to one G-quadruplex DNA molecule, but also explained the “light switch” effect.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Metal-binding and redox properties of substituted linear and cyclic ATCUN
           motifs
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Kosh P. Neupane , Amanda R. Aldous , Joshua A. Kritzer
      The amino-terminal copper and nickel binding (ATCUN) motif is a short peptide sequence found in human serum albumin and other proteins. Synthetic ATCUN–metal complexes have been used to oxidatively cleave proteins and DNA, cross-link proteins, and damage cancer cells. The ATCUN motif consists of a tripeptide that coordinates Cu(II) and Ni(II) ions in a square planar geometry, anchored by chelation sites at the N-terminal amine, histidine imidazole and two backbone amides. Many studies have shown that the histidine is required for tight binding and square planar geometry. Previously, we showed that macrocyclization of the ATCUN motif can lead to high-affinity binding with altered metal ion selectivity and enhanced Cu(II)/Cu(III) redox cycling (Inorg. Chem. 2013, 52, 2729–2735). In this work, we synthesize and characterize several linear and cyclic ATCUN variants to explore how substitutions at the histidine alter the metal-binding and catalytic properties. UV–visible spectroscopy, EPR spectroscopy and mass spectrometry indicate that cyclization can promote the formation of ATCUN-like complexes even in the absence of imidazole. We also report several novel ATCUN-like complexes and quantify their redox properties. These findings further demonstrate the effects of conformational constraints on short, metal-binding peptides, and also provide novel redox-active metallopeptides suitable for testing as catalysts for stereoselective or regioselective oxidation reactions.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Occupational exposure to aluminum and its amyloidogenic link with
           cognitive functions
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): N.H. Zawilla , F.M. Taha , N.A. Kishk , S.A. Farahat , M. Farghaly , M. Hussein
      As many other metals, aluminum is a widely recognized neurotoxicant and its link with neurodegenerative disorders has been the subject of scientific debate. One proposal focuses on amyloid β deposition (amyloidogenesis) as the key player in triggering neuronal dysfunction the so-called amyloid cascade hypothesis. We undertook this study first to investigate the cognition status of workers exposed to Al dust in an Al factory in Southern Cairo, second, to evaluate serum amyloid precursor protein (APP) and cathepsin D (CD) enzyme activity to study the possible role of Al in amyloidogenesis, and finally to explore the relation between these potential biomarkers and cognitive functions. The study was conducted on 54 exposed workers and 51 matched controls. They were subjected to questionnaire, neurological examination and a cognitive test battery, Addenbrooke's Cognitive Examination — Revised (ACE-R). Serum Al, APP and CD enzyme activity were measured. A significant increase of serum Al was found in the exposed workers with an associated increase in serum APP and decrement in CD activity. The exposed workers displayed poor performance on the ACE-R test. No significant correlation was detected between ACE-R test total score and either APP or CD activity. We concluded that occupational exposure to Al is associated with cognitive impairment. The effect of occupational Al exposure on the serum levels of APP and CD activity may be regarded as a possible mechanism of Al in amyloidogenesis. However, our findings do not support the utility of serum APP and CD activity as screening markers for early or preclinical cognitive impairment.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Copper(II), nickel(II) and zinc(II) complexes of the N-terminal
           nonapeptide fragment of amyloid-β and its derivatives
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Ágnes Grenács , Imre Sóvágó
      Copper(II), nickel(II) and zinc(II) complexes of the nonapeptide fragment of amyloid-β Aβ(1–9) (NH2-DAEFRHDSG-NH2) and its two derivatives: NH2-DAAAAHAAA-NH2 and NH2-DAAAAAHAA-NH2 have been studied by potentiometric, UV–visible and CD spectroscopic methods. The results reveal the primary role of the amino terminus of peptides in copper(II) and nickel(II) binding. The formation of dinuclear complexes was also possible in the copper(II) containing systems but only the first six amino acids from the amino terminus were involved in metal binding in the physiologically relevant pH range. The coordination chemistry of the two alanine mutated peptides is almost the same as that of the native nonapeptide, but the thermodynamic stability of the copper(II) complexes of the mutants is significantly reduced. This difference probably comes from the secondary interactions of the polar side chains of Asp, Glu, Ser and Arg residues present in the native peptide. Moreover, this difference reveals that the amino acid sequence of the N-terminal domains of amyloid peptides is especially well suited for the complexation with copper(II) ions.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Synthesis, characterization and binding affinities of rhenium(I)
           thiosemicarbazone complexes for the estrogen receptor (α/β)
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Ara Núñez-Montenegro , Rosa Carballo , Ezequiel M. Vázquez-López
      The binding affinities towards estrogen receptors (ERs) α and β of a set of thiosemicarbazone ligands (HLn) and their rhenium(I) carbonyl complexes [ReX(HLn)(CO)3] (X=Cl, Br) were determined by a competitive standard radiometric assay with [3H]-estradiol. The ability of the coordinated thiosemicarbazone ligands to undergo deprotonation and the lability of the ReX bond were used as a synthetic strategy to obtain [Re(hpy)(Ln)(CO)3] (hpy=3- or 4-hydroxypyridine). The inclusion of the additional hpy ligand endows the new thiosemicarbazonate complexes with an improved affinity towards the estrogen receptors and, consequently, the values of the inhibition constant (Ki) could be determined for some of them. In general, the values of Ki for both ER subtypes suggest an appreciable selectivity towards ERα.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Synthesis and properties of a new micellar
           polyphosphazene–platinum(II) conjugate drug
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Prakash G. Avaji , Hye In Joo , Jung Hyun Park , Kyung Su Park , Yong Joo Jun , Hwa Jeong Lee , Youn Soo Sohn
      Aiming at tumor targeting delivery of oxaliplatin using polymer therapy, a new monomeric platinum(II) complex (dach)Pt[HEDM] (dach: trans-(±)-1,2-diaminocyclohexane; HEDM: 2-hydroxyethoxydiethylmalate) was designed to include the antitumor moiety (dach)Pt and HEDM as a linker to the polyphosphazene backbone. This monomeric Pt-complex could easily be grafted to the PEGylated polyphosphazene backbone to prepare a novel polyphosphazene–Pt conjugate, [NP(MPEG550)(dach)Pt(EM)]n [MPEG550: methoxy poly(ethylene glycol) with an average molecular weight of 550; EM: ethoxymalate]. This amphiphilic polyphosphazene–Pt conjugate was found to self-assemble into stable polymeric micelles of a mean diameter of 130nm, which is suitable for passive tumor targeting by enhanced permeability and retention (EPR) effect. Pharmacokinetic study of this polymer conjugate exhibited long blood circulation as expected and longer half-life (t1/2β=9.52h) compared with oxaliplatin (3.47h), and much larger AUC (area under the curve) value (25,831ng·h/mL) compared with oxaliplatin (1194ng·h/mL). Biodistribution study of the polymer conjugate has shown excellent tumor selectivity with the tumor to tissue ratio of 3.84 at 2h post injection and 11.7 at 24h post injection probably due to the EPR effect of the polymer conjugate while no tumor selectivity was observed for monomeric oxaliplatin. Furthermore, accumulation of this polymer conjugate in kidney was much lower compared with oxaliplatin. Also the nude mouse xenograft trial of the polymer conjugate has shown higher antitumor efficacy compared with oxaliplatin.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Curcumin derivatives as metal-chelating agents with potential
           multifunctional activity for pharmaceutical applications
    • Abstract: Publication date: October 2014
      Source:Journal of Inorganic Biochemistry, Volume 139
      Author(s): Erika Ferrari , Rois Benassi , Stefania Sacchi , Francesca Pignedoli , Mattia Asti , Monica Saladini
      Curcuminoids represent new perspectives for the development of novel therapeutics for Alzheimer's disease (AD), one probable mechanism of action is related to their metal complexing ability. In this work we examined the metal complexing ability of substituted curcuminoids to propose new chelating molecules with biological properties comparable with curcumin but with improved stability as new potential AD therapeutic agents. The K2T derivatives originate from the insertion of a -CH2COOC(CH3)3 group on the central atom of the diketonic moiety of curcumin. They retain the diketo-ketoenol tautomerism which is solvent dependent. In aqueous solution the prevalent form is the diketo one but the addition of metal ion (Ga3+, Cu2+) causes the dissociation of the enolic proton creating chelate complexes and shifting the tautomeric equilibrium towards the keto–enol form. The formation of metal complexes is followed by both NMR and UV–vis spectroscopy. The density functional theory (DFT) calculations on K2T21 complexes with Ga3+ and Cu2+ are performed and compared with those on curcumin complexes. [Ga(K2T21)2(H2O)2]+ was found more stable than curcumin one. Good agreement is detected between calculated and experimental 1H and 13C NMR data. The calculated OH bond dissociation energy (BDE) and the OH proton dissociation enthalpy (PDE), allowed to predict the radical scavenging ability of the metal ion complexed with K2T21, while the calculated electronic affinity (EA) and ionization potential (IP) represent yardsticks of antioxidant properties. Eventually theoretical calculations suggest that the proton-transfer-associated superoxide-scavenging activity is enhanced after binding metal ions, and that Ga3+ complexes display possible superoxide dismutase (SOD)-like activity.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Cellular uptake and cytotoxicity of a near-IR fluorescent
           corrole–TiO2 nanoconjugate
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Carl M. Blumenfeld , Bryce F. Sadtler , G. Esteban Fernandez , Lily Dara , Cathie Nguyen , Felix Alonso-Valenteen , Lali Medina-Kauwe , Rex A. Moats , Nathan S. Lewis , Robert H. Grubbs , Harry B. Gray , Karn Sorasaenee
      We are investigating the biological and biomedical imaging roles and impacts of fluorescent metallocorrole–TiO2 nanoconjugates as potential near-infrared optical contrast agents in vitro in cancer and normal cell lines. The TiO2 nanoconjugate labeled with the small molecule 2,17-bis(chlorosulfonyl)-5,10,15-tris(pentafluorophenyl)corrolato aluminum(III) (1-Al–TiO2) was prepared. The nanoparticle 1-Al–TiO2 was characterized by transmission electron microscopy (TEM) and integrating-sphere electronic absorption spectroscopy. TEM images of three different samples of TiO2 nanoparticles (bare, H2O2 etched, and 1-Al functionalized) showed similarity in shapes and sizes with an average diameter of 29nm for 1-Al–TiO2. Loading of 1-Al on the TiO2 surfaces was determined to be ca. 20–40mg 1-Al/g TiO2. Confocal fluorescence microscopy (CFM) studies of luciferase-transfected primary human glioblastoma U87-Luc cells treated with the nanoconjugate 1-Al–TiO2 as the contrast agent in various concentrations were performed. The CFM images revealed that 1-Al–TiO2 was found inside the cancer cells even at low doses (0.02–2μg/mL) and localized in the cytosol. Bioluminescence studies of the U87-Luc cells exposed to various amounts of 1-Al–TiO2 showed minimal cytotoxic effects even at higher doses (2–2000μg/mL) after 24h. A similar observation was made using primary mouse hepatocytes (PMH) treated with 1-Al–TiO2 at low doses (0.0003–3μg/mL). Longer incubation times (after 48 and 72h for U87-Luc) and higher doses (>20μg/mL 1-Al–TiO2 for U87-Luc and >3μg/mL 1-Al–TiO2 for PMH) showed decreased cell viability.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • A rhodium(III) complex inhibits LPS-induced nitric oxide production and
           angiogenic activity in cellulo
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Li-Juan Liu , Sheng Lin , Daniel Shiu-Hin Chan , Chi Teng Vong , Pui Man Hoi , Chun-Yuen Wong , Dik-Lung Ma , Chung-Hang Leung
      Metal-containing complexes have arisen as viable alternatives to organic molecules as therapeutic agents. Metal complexes possess a number of advantages compared to conventional carbon-based compounds, such as distinct geometries, interesting electronic properties, variable oxidation states and the ability to arrange different ligands around the metal centre in a precise fashion. Meanwhile, nitric oxide (NO) plays key roles in the regulation of angiogenesis, vascular permeability and inflammation. We herein report a novel cyclometalated rhodium(III) complex as an inhibitor of lipopolysaccharides (LPS)-induced NO production in RAW264.7 macrophages. Experiments suggested that the inhibition of NO production in cells by complex 1 was mediated through the down-regulation of nuclear factor-κB (NF-κB) activity. Furthermore, complex 1 inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs) as revealed by an endothelial tube formation assay. This study demonstrates that kinetically inert rhodium(III) complexes may be potentially developed as effective anti-angiogenic agents.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Introduction of water into the heme distal side by Leu65 mutations of an
           oxygen sensor, YddV, generates verdoheme and carbon monoxide, exerting the
           heme oxygenase reaction
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Martin Stranava , Markéta Martínková , Marie Stiborová , Petr Man , Kenichi Kitanishi , Lucie Muchová , Libor Vítek , Václav Martínek , Toru Shimizu
      The globin-coupled oxygen sensor, YddV, is a heme-based oxygen sensor diguanylate cyclase. Oxygen binding to the heme Fe(II) complex in the N-terminal sensor domain of this enzyme substantially enhances its diguanylate cyclase activity which is conducted in the C-terminal functional domain. Leu65 is located on the heme distal side and is important for keeping the stability of the heme Fe(II)–O2 complex by preventing the entry of the water molecule to the heme complex. In the present study, it was found that (i) Escherichia coli-overexpressed and purified L65N mutant of the isolated heme-bound domain of YddV (YddV-heme) contained the verdoheme iron complex and other modified heme complexes as determined by optical absorption spectroscopy and mass spectrometry; (ii) CO was generated in the reconstituted system composed of heme-bound L65N and NADPH:cytochrome P450 reductase as confirmed by gas chromatography; (iii) CO generation of heme-bound L65N in the reconstituted system was inhibited by superoxide dismutase and catalase. In a concordance with the result, the reactive oxygen species increased the CO generation; (iv) the E. coli cells overexpressing the L65N protein of YddV-heme also formed significant amounts of CO compared to the cells overexpressing the wild type protein; (v) generation of verdoheme and CO was also observed for other mutants at Leu65 as well, but to a lesser extent. Since Leu65 mutations are assumed to introduce the water molecule into the heme distal side of YddV-heme, it is suggested that the water molecule would significantly contribute to facilitating heme oxygenase reactions for the Leu65 mutants.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • High metal substitution tolerance of anthrax lethal factor and
           characterization of its active copper-substituted analogue
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Suet Y. Lo , Crystal E. Säbel , Michael I. Webb , Charles J. Walsby , Stefan Siemann
      Anthrax lethal factor (LF) is a zinc-dependent metalloendopeptidase and a member of the gluzincin family. The current report demonstrates a high metal substitution tolerance of LF atypical of gluzincins and other zinc-dependent metalloproteases. Mn2+, Co2+, Ni2+, Cu2+ and Cd2+ were found to reactivate the apoprotein of LF to a level either comparable to or significantly higher than that noted for the native zinc enzyme. The most active form of LF was obtained with Cu2+, a surprising observation since most Cu2+-substituted zinc proteases display very low activity. Cu2+-substituted LF (CuLF), prepared by direct exchange and by apoprotein reconstitution methodologies, displayed a several-fold higher catalytic competence towards chromogenic and fluorogenic LF substrates than native LF. CuLF bound Cu2+ tightly with a dissociation constant in the femtomolar range. The electron paramagnetic resonance spectrum of CuLF revealed the protein-bound metal ion to be coordinated to two nitrogen donor atoms, suggesting that Cu2+ binds to both active site histidine residues. While ZnLF and CuLF (prepared by direct exchange) were capable of killing RAW 264.7 murine macrophage-like cells, apoLF and all metal-reconstituted apoprotein preparations failed to elicit a cytotoxic response. Competition experiments using apoLF/ZnLF mixtures demonstrated the propensity of apoLF to relieve ZnLF-induced cell death, suggesting that both protein forms can compete with each other for binding to protective antigen. The lack of cytotoxicity of apoLF and its metal-reconstituted variants likely originates from structural perturbations in these proteins which might prevent their translocation into the cytoplasm.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Proton pumping by an inactive structural variant of cytochrome c oxidase
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Emelie Svahn , Kristina Faxén , Robert B. Gennis , Peter Brzezinski
      The aa 3-type cytochrome c oxidases (CytcOs) from e.g. Rhodobacter sphaeroides and Paracoccus denitrificans harbor two proton-transfer pathways. The K pathway is used for proton uptake upon reduction of the CytcO, while the D pathway is used after binding of O2 to the catalytic site. The aim of the present study was to determine whether or not CytcO in which the K pathway is blocked (by e.g. the Lys362Met replacement) is capable of pumping protons. The process can not be studied using conventional assays because the O2-reduction activity is too low when the K pathway is blocked. Consequently, proton pumping with a blocked K pathway has not been demonstrated directly. Here, the Lys362Met and Ser299Glu structural variants were reconstituted in liposomes and allowed to (slowly) become completely reduced. Then, the reaction with O2 was studied with μs time resolution after flash photolysis of a blocking CO ligand bound to heme a 3. The data show that with both the inactive Lys362Met and partly active Ser299Glu variants proton release occurred with the same time constants as with the wild-type oxidase, i.e. ~200μs and ~3ms, corresponding in time to formation of the ferryl and oxidized states, respectively. Thus, the data show that the K pathway is not required for proton pumping, suggesting that D and K pathways operate independently of each other after binding of O2 to the catalytic site.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Light-stable bis(norharmane)silver(I) compounds: Synthesis,
           characterization and antiproliferative effects in cancer cells
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Rais Ahmad Khan , Khalid Al-Farhan , Andreia de Almeida , Ali Alsalme , Angela Casini , Mohamed Ghazzali , Jan Reedijk
      Four different-anion Ag(I) compounds with the ligand norharmane (9H-Pyrido[3,4-b]indole; Hnor) and having the general formula [Ag(Hnor)2](anion) (anion=ClO4 −, NO3 − and BF4 −) [Ag(Hnor)2(MeCN)](PF6) are reported, and studied in detail regarding their coordination mode and in vitro antiproliferative effects. X-ray structural analysis revealed that the complex with the PF6 − anion has a MeCN solvent molecule weakly coordinated to Ag(I), making the metal coordination T-shaped, while the other compounds present the classical linear Ag(I) coordination. The compounds showed certain cell growth inhibitory effects in two different cancer cell lines, with the perchlorate containing complex being the most toxic and in fact comparable to cisplatin. Notably, the compounds are stable in visible light; and the luminescence in the solid state was found to be extremely weak, whereas in MeOH solution all compounds show a moderate to weak emission band at 375nm, when excited at 290nm.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • A.SigelH.SigelR.K.O.SigelInterrelations between Essential Metal Ions and
           Human DiseasesMetal Ions in Life Sciencesvol.
           132013SpringerDordrecht978-94-007-7499-5
    • Abstract: Publication date: Available online 8 June 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Hui Chao



      PubDate: 2014-06-09T15:50:10Z
       
  • Interaction of Pd2+ complexes of 2,6-disubstituted pyridines with
           nucleoside 5´-monophosphates
    • Abstract: Publication date: Available online 5 June 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Oleg Golubev , Tuomas Lönnberg , Harri Lönnberg
      To learn more about the underlying principles of metal-ion-mediated recognition of nucleic acid bases, PdCl+ complexes of six 2,6-disubstituted pyridines, viz. pyridine-2,6-dicarboxamide, its N 2,N 6-dimethyl and N 2,N 6-diisopropyl derivatives, 6-carbamoylpyridine-2-carboxylic acid, 6-aminomethylpyridine-2-carboxamide and its N 2-methyl derivative, were prepared and their interaction with nucleoside 5´-monophosphate (NMP) was studied by 1H NMR spectroscopy in D2O at pH7.2. The binding sites within the nucleobases were assigned on the basis of Pd2+ induced changes in chemical shifts of the base moiety proton resonances. The mole fractions of NMPs engaged in mono- or dinuclear Pd2+ complexes were determined at various concentrations by comparing the intensities of the aromatic and anomeric protons of the complexed and uncomplexed NMPs. Some of the pyridine complexes showed moderate discrimination between the NMPs.
      Graphical abstract image Highlights To learn more about the underlying principles of metal-ion-mediated recognition of nucleic acid bases, PdCl+ complexes of six 2,6-disubstituted pyridines were prepared and their interaction with nucleoside 5´-monophosphate (NMP) was studied by 1H NMR spectroscopy in D2O at pH7.2.

      PubDate: 2014-06-09T15:50:10Z
       
  • Contents
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137




      PubDate: 2014-06-09T15:50:10Z
       
  • Ferrocene and (arene)ruthenium(II) complexes of the natural anticancer
           naphthoquinone plumbagin with enhanced efficacy against resistant cancer
           cells and a genuine mode of action
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138
      Author(s): Cornelia Spoerlein-Guettler , Katharina Mahal , Rainer Schobert , Bernhard Biersack
      A series of ferrocene and (arene)ruthenium(II) complexes attached to the naturally occurring anticancer naphthoquinones plumbagin and juglone was tested for efficacy against various cancer cell lines and for alterations in the mode of action. The plumbagin ferrocene and (p-cymene)Ru(II) conjugates 1c and 2a overcame the multi-drug drug resistance of KB-V1/Vbl cervix carcinoma cells and showed IC50 (72h) values around 1μM in growth inhibition assays using 3-(4,5-dimethyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT). They were further investigated for their influence on the cell cycle of KB-V1/Vbl and HCT-116 colon carcinoma cells, on the generation of reactive oxygen species (ROS) by the latter cell line, for their substrate character for the P-glycoprotein drug eflux pump via the calcein-AM efflux assays, and for DNA affinity by the electrophoretic mobility shift assay (EMSA). The derivatives 1c and 2a increased the number of dead cancer cells (sub-G0/G1 fraction) in a dose- and time-dependent manner. ROS levels were significantly increased upon treatment with 1c and 2a. These compounds also showed a greater affinity to linear DNA than plumbagin. While plumbagin did not affect calcein-AM transport by P-glycoprotein the derivatives 1c and 2a exhibited a 50% or 80% inhibition of the P-glycoprotein-mediated calcein-AM efflux relative to the clinically established sensitizer verapamil.
      Graphical abstract image

      PubDate: 2014-06-09T15:50:10Z
       
  • Editorial Board
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137




      PubDate: 2014-06-09T15:50:10Z
       
  • Enantioselective DNA condensation induced by heptameric lanthanum helical
           supramolecular enantiomers
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138
      Author(s): Fei-Fei Bao , Xin-Xin Xu , Wen Zhou , Chun-Yan Pang , Zaijun Li , Zhi-Guo Gu
      DNA condensation induced by a pair of heptameric La(III) helical enantiomers M-[La7(S-L)6(CO3)(NO3)6(OCH3)(CH3OH)7]·2CH3OH·5H2O and P-[La7(R-L)6(CO3)(NO3)6(OCH3)(CH3OH)5(H2O)2]·2CH3OH·4H2O ( M -La and P -La, L=2-(2-hydroxybenzylamino)-3-carbamoylpropanoic acid) has been investigated by UV/vis spectroscopy, fluorescence spectroscopy, CD spectroscopy, EMSA, RALS, DLS, and SEM. The enantiomers M -La and P -La could induce CT-DNA condensation at a low concentration as observed in UV/vis spectroscopy. DNA condensates possessed globular nanoparticles with nearly homogeneous sizes in solid state determined by SEM (ca. 250nm for M -La and ca. 200nm for P -La). The enantiomers bound to DNA through electrostatic attraction and hydrogen bond interactions in a major groove, and rapidly condensed free DNA into its compact state. DNA decompaction has been acquired by using EDTA as disassembly agent, and analyzed by UV/vis spectroscopy, CD spectroscopy and EMSA. Moreover, the enantiomers M -La and P -La displayed discernible discrimination in DNA interaction and DNA condensation, as well as DNA decondensation. Our study suggested that lanthanum(III) enantiomers M -La and P -La were efficient DNA packaging agents with potential applications in gene delivery.
      Graphical abstract image

      PubDate: 2014-06-09T15:50:10Z
       
  • Copper(II) Complexes of Alloferon 1 with Point Mutations (H1A) and (H9A)
           Stability Structure and Biological Activity
    • Abstract: Publication date: Available online 2 June 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Agnieszka Matusiak , Mariola Kuczer , Elżbieta Czarniewska , Grzegorz Rosiński , Teresa Kowalik-Jankowska
      Mono- and polynuclear copper(II) complexes of the alloferon 1 with point mutations (H1A) A1GVSGH6GQH9GVH12G (Allo1A) and (H9A) H1GVSGH6GQA9GVH12G (Allo9A) have been studied by potentiometric, UV-visible, CD, EPR spectroscopic and mass spectrometry (MS) methods. To obtain a complete complex speciation different metal-to-ligand molar ratios ranging from 1:1 to 4:1 for Allo1A and to 3:1 for Allo9A were studied. The presence of the His residue in first position of the peptide chain changes the coordination abilities of the Allo9A peptide in comparison to that of the Allo1A. Imidazole-N3 atom of N-terminal His residue of the Allo9A peptide forms stable 6-membered chelate with the terminal amino group. Furthermore, the presence of two additional histidine residues in the Allo9A peptide (H6,H12) leads to the formation of the CuL complex with 4N {NH2,NIm-H1,NIm-H6,NIm-H12} binding site in wide pH range (5-8). For the Cu(II)-Allo1A system, the results demonstrated that at physiological pH7.4 the predominant complex the CuH-1 L consists of the 3N {NH2, N-,CO,NIm} coordination mode. The inductions of phenoloxidase activity and apoptosis in vivo in Tenebrio molitor cells by the ligands and their copper(II) complexes at pH7.4 were studied. The Allo1A, Allo1K peptides and their copper(II) complexes displayed the lowest haemocytotoxic activity while the most active was the Cu(II)-Allo9A complex formed at pH7.4. The results may suggest that the N-terminal-His1 and His6 residues may be more important for their proapoptotic properties in insects than those at positions 9 and 12 in the peptide chain.
      Graphical abstract image

      PubDate: 2014-06-03T14:58:10Z
       
  • The impact of synthetic analogs of histidine on copper(II) and nickel(II)
           coordination properties to an albumin-like peptide. Possible leads towards
           new metallodrugs
    • Abstract: Publication date: Available online 2 June 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Izabela Zawisza , Mariusz Mital , Agnieszka Polkowska-Nowakowska , Arkadiusz Bonna , Wojciech Bal
      The purpose of our research was to obtain peptidomimetics possessing Cu(II) and Ni(II) binding properties, which would be useful for biomedical applications. In this context we used potentiometry, UV-VIS and CD spectroscopies to characterize the Cu(II) and Ni(II) binding properties of pentapeptide analogs of the N-terminal sequence of histatin 5. The peptides investigated had a general sequence DSXAK-am (am stands for C-terminal amide), with X including His and its three synthetic analogs, (4-thiazolyl)-L-alanine (1), (2-pyridyl)-L-alanine (2), and (pyrazol-1-yl)-L-alanine (3). The heterocyclic nitrogens present in these analogs were significantly more acidic than that of the His imidazole. We found that DSXAK-am peptides were able to bind Cu(II) and Ni(II) and form 4N complexes in a cooperative fashion, with similar affinities. These results indicate that acidic heterocyclic amino acids provide a viable alternative for histidine in peptidomimetics designed for metal ions binding.
      Graphical abstract image

      PubDate: 2014-06-03T14:58:10Z
       
  • Spectroscopic studies on HasA from Yersinia pseudotuberculosis
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138
      Author(s): Shin-ichi Ozaki , Takehiro Sato , Yukari Sekine , Catharina T. Migita , Takeshi Uchida , Koichiro Ishimori
      Heme acquisition system A (HasA) is known as a hemophore in Gram-negative pathogens. The ferric heme iron is coordinated by Tyr-75 and His-32 in holo-HasA from Pseudomonas aeruginosa (HasApa). In contrast, in holo-HasA from Yersinia pseudotuberculosis (HasAyp), our spectroscopic studies suggest that only Tyr-75 coordinates to the ferric heme iron. The substitution of Gln-32 with alanine in HasAyp does not alter the spectroscopic properties, indicating that Gln-32 is not an axial ligand for the heme iron. Somewhat surprisingly, the Y75A mutant of HasAyp can capture a free hemin molecule but the rate of hemin uptake is slower than that of wild type, suggesting that the hydrophobic interaction in the heme pocket may also play a role in heme acquisition. Unlike in wild type apoprotein, ferric heme transfer from Hb to Y75A apo-HasAyp has not been observed. These results imply that coordination (bonding/interaction) between Tyr-75 and the heme iron is important for heme transfer from Hb. Interestingly, HasAyp differs from HasApa in its ability to bind the ferrous heme iron. Apo-HasAyp can capture ferrous heme and resonance Raman spectra of ferrous-carbon monoxide holo-HasAyp suggest that Tyr-75 is protonated when the heme iron is in the ferrous state. The ability of HasAyp to acquire the ferrous heme iron might be beneficial to Y. pseudotuberculosis, a facultative anaerobe in the Enterobacteriaceae family.
      Graphical abstract image

      PubDate: 2014-05-27T11:29:22Z
       
  • Proton and gallium(III) binding properties of a biologically active
           salicylidene acylhydrazide
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138
      Author(s): Shoghik Hakobyan , Jean-François Boily , Madeleine Ramstedt
      Bacterial biofilm formation causes a range of problems in our society, especially in health care. Salicylidene acylhydrazides (hydrazones) are promising antivirulence drugs targeting secretion systems used during bacterial infection of host cells. When mixed with the gallium ion they become especially potent as bacterial and biofilm growth-suppressing agents, although the mechanisms through which this occurs are not fully understood. At the base of this uncertainty lies the nature of hydrazone–metal interactions. This study addresses this issue by resolving the equilibrium speciation of hydrazone–gallium aqueous solutions. The protonation constants of the target 2-oxo-2-[N-(2,4,6-trihydroxy-benzylidene)-hydrazino]-acetamide (ME0163) hydrazone species and of its 2,4,6-trihydroxybenzaldehyde and oxamic acid hydrazide building blocks were determined by UV–visible spectrophotometry to achieve this goal. These studies show that the hydrazone is an excessively strong complexing agent for gallium and that its antivirulence properties are predominantly ascribed to monomeric 1:1Ga–ME0163 complexes of various Ga hydrolysis and ME0163 protonation states. The chelation of Ga(III) to the hydrazone also increased the stability of the compounds against acid-induced hydrolysis, making this group of compounds very interesting for biological applications where the Fe-antagonist action of both Ga(III) and the hydrazone can be combined for enhanced biological effect.
      Graphical abstract image

      PubDate: 2014-05-22T11:23:52Z
       
  • Silver(I)/6-hydroxyiminolumazine compounds differently modify
           renin-angiotensin system-regulating aminopeptidases A and N in human
           neuroblastoma and glioma cells
    • Abstract: Publication date: Available online 21 May 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Mª. Jesús Ramírez-Expósito , Mª. Dolores Mayas-Torres , Mª. Pilar Carrera-González , Sonia B. Jiménez-Pulido , Nuria A. Illán-Cabeza , Purificación Sánchez-Sánchez , Francisco Hueso-Ureña , José M. Martínez-Martos , Miguel N. Moreno-Carretero
      We have described that local tissue renin-angiotensin-system (RAS) is involved in tumor growth in a rat model of experimental glioma in vivo, through the modification of their corresponding local proteolytic regulatory enzymes. Thus, we have found a time-dependent significant decrease in aminopeptidase N (APN) and a significant increase in aminopeptidase A (APA) activities concomitantly with tumor growth in tumor tissue whereas no changes were found in circulating aminopeptidase activities; we suggested that angiotensin peptides may play an essential step in both tumor infiltration and associated angiogenesis. Here we analyze in vitro the antiproliferative efficacy, apoptotic properties and effects of three new disilver complexes containing E-6-(hydroxyimino)ethyl-1,3,7-trimethyllumazine (lumazine=pteridine-2,4(1H,3H)-dione) on RAS-regulating APA and APN specific activities in human neuroblastoma and glioma cell lines NB69 and U373-MG. Disilver compounds showed cytotoxicity against both cell lines, although their potency was different for each cell type. Furthermore, NB69 cells need higher concentrations of silver complexes than U373-MG cells to obtain a 50% growth inhibition. All compounds showed apoptotic effects, being U373-MG cells more susceptible. The three silver complexes tested also show a dose-dependent inhibitory effect on APA activity in NB69 and U373-MG cells, although U373-MG cells are more sensitive. On the contrary, none of them showed effects on APN activity in NB69 neuroblastoma cells whereas the three compounds showed a dose-dependent stimulatory effect on APN activity in U373-MG glioma cells with a similar potency. Disilver complexes show specific antitumor activity against brain tumor cells acting through the paracrine regulating system mediated by local tissue RAS.
      Graphical abstract image

      PubDate: 2014-05-22T11:23:52Z
       
  • The gallium(III)–salicylidene acylhydrazide complex shows
           synergistic anti-biofilm effect and inhibits toxin production by
           Pseudomonas aeruginosa
    • Abstract: Publication date: September 2014
      Source:Journal of Inorganic Biochemistry, Volume 138
      Author(s): Olena Rzhepishevska , Shoghik Hakobyan , Barbro Ekstrand-Hammarström , Yvonne Nygren , Torbjörn Karlsson , Anders Bucht , Mikael Elofsson , Jean-François Boily , Madeleine Ramstedt
      Bacterial biofilms cause a range of problems in many areas and especially in health care. Biofilms are difficult to eradicate with traditional antibiotics and consequently there is a need for alternative ways to prevent and/or remove bacterial biofilms. Furthermore, the emergence of antibiotic resistance in bacteria creates a challenge to find new types of antibiotics with a lower evolutionary pressure for resistance development. One route to develop such drugs is to target the so called virulence factors, i.e. bacterial systems used when bacteria infect a host cell. This study investigates synergy effects between Ga(III) ions, previously reported to suppress biofilm formation and growth in bacteria, and salicylidene acylhydrazides (hydrazones) that have been proposed as antivirulence drugs targeting the type three secretion system used by several Gram-negative pathogens, including Pseudomonas aerugionosa, during bacterial infection of host cells. A library of hydrazones was screened for: Fe(III) binding, enhanced anti-biofilm effect with Ga(III) on P. aeruginosa, and low cytotoxicity to mammalian cells. The metal coordination for the most promising ligand, 2-Oxo-2-[N-(2,4,6-trihydroxy-benzylidene)-hydrazino]-acetamide (ME0163) with Ga(III) was investigated using extended X-ray absorption fine structure spectroscopy as well as density functional theory. The results showed that Ga(III) chelates the hydrazone with 5- and 6-membered chelating rings, and that the Ga(III)–ME0163 complex enhanced the antibiofilm effect of Ga(III) while suppressing the type three secretion system in P. aeruginosa. The latter effect was not observed for the hydrazone alone and was similar for Ga(III)–citrate and Ga(III)–ME0163 complexes, indicating that the inhibition of virulence was caused by Ga(III).
      Graphical abstract image

      PubDate: 2014-05-22T11:23:52Z
       
  • Lanthanide complexes containing 5-methyl-1,2,4-triazolo[1,5-a]
           pyrimidin-7(4h)-one and their therapeutic potential to fight leishmaniasis
           and Chagas disease
    • Abstract: Publication date: Available online 6 May 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Ana B. Caballero , Antonio Rodríguez-Diéguez , Juan M. Salas , Manuel Sánchez-Moreno , Clotilde Marín , Inmaculada Ramírez-Macías , Noelia Santamaría-Díaz , Ramón Gutierrez-Sánchez
      In the last years, numerous and significant advances in lanthanide coordination chemistry have been achieved. The unique chemical nature of these metal ions which is conferred by their f-electrons, have led to a wide range of coordination compounds with interesting structural, physical and also biological properties. Consequently, lanthanide complexes have found applications mainly in catalysis, gas adsorption, photochemistry and as diagnostic tools. However, research on their therapeutic potential and the understanding of their mechanism of action is still taking its first steps, and there is a distinct lack of research in the parasitology field. In the present work, we describe the synthesis and physical properties of seven new lanthanide complexes with the anionic form of the bioactive ligand 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO), namely [Ln(mtpO)3(H2O)6]·9H2O (Ln=La(III), Nd(III), Eu(III), Gd(III), Tb(III), Dy(III), Er(III)). In addition, results on the in vitro antiproliferative activity against Leishmania spp. and Trypanosoma cruzi are described. The high activity of the new compounds against parasite proliferation and their low cytotoxicity against reference host cell lines show a great potential of this type of compounds to become a new generation of highly effective and non-toxic antiparasitic agents to fight the so considered neglected diseases leishmaniasis and Chagas disease.
      Graphical abstract image

      PubDate: 2014-05-09T21:28:27Z
       
  • New bioactive 2,6-diacetylpyridine bis(p-chlorophenylthiosemicarbazone)
           ligand and its Pd(II) and Pt(II) complexes: Synthesis, characterization,
           cytotoxic activity and DNA binding ability
    • Abstract: Publication date: Available online 9 May 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Ana I. Matesanz , Carolina Hernández , Pilar Souza
      Preparation and characterization of 2,6-diacetylpyridine bis(4 N-p-chlorophenylthiosemicarbazone) ligand, H2L, and its palladium(II) and platinum(II) complexes [PdL] and [PtL], is described. The molecular structure of the two new complexes has been determined by single crystal X-ray diffraction. The ligand act as dianionic tetradentate donor coordinating to the metal center in a square planar geometry through the pyridine nitrogen atom and the azomethine nitrogen and thione sulfur atoms from one thiosemicarbazone arm, the fourth coordination position is occupied by the hydrazine nitrogen atom of the other arm. New free ligand and its metal complexes have been evaluated for antiproliferative activity in vitro against NCI-H460, T-47D, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest that these compounds may be endowed with important antitumor properties, especially H2L and [PtL] since they are capable of not only circumvent cisplatin resistance in A2780cisR cells but also exhibit high antiproliferative activity in breast cancer T-47D cells. The interaction of H2L with calf thymus DNA was also investigated and its binding constant (Kb) determined.
      Graphical abstract image

      PubDate: 2014-05-09T21:28:27Z
       
  • Complexing ability of (-)-cytisine – synthesis, spectroscopy and
           crystal structures of the new copper and zinc complexes
    • Abstract: Publication date: Available online 9 May 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Anna K. Przybył , Maciej Kubicki , Renata Jastrząb
      For the first time the NMR spectra of quinolizidine alkaloid with Cu(II) are studied. Structures of new complexes of (-)-cytisine with Cu+2 and Zn+2 cations are visualized, discussed in detail and characterized by spectroscopic methods: ESI-MS, NMR, UV-vis, EPR and crystallographic methods. In solution metal coordinates through the protonated nitrogen atoms of secondary amino groups (in piperidine ring) of cytisine molecule. While in solid state the most stable structures of the complexes are those in which the coordination of Cu(II) and Zn(II) salts is realized solely through the lactam carbonyl oxygen atom.
      Graphical abstract image

      PubDate: 2014-05-09T21:28:27Z
       
  • Tyrosine nitration in peptides by peroxynitrite generated in situ in a
           light-controlled platform: Effects of pH and thiols
    • Abstract: Publication date: Available online 9 May 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Tara R. deBoer , Rafael I. Palomino , Sharon O. Idiga , Glenn L. Millhauser , Pradip K. Mascharak
      Peroxynitrite has been shown to play a critical role in inflammation and affords 3-nitrotyrosine as the hallmark product. The reported methods of generating this reactive nitrogen species in situ often fails to provide a high and steady flux of peroxynitrite resulting in poor yields of 3-nitrotyrosine. Herein we report a two-component peroxynitrite-generating platform in which this anion is produced in a biomimetic fashion and under the control of visible light. Incorporation of the nitric oxide- and superoxide-generating components in polymer matrices allows easy alterations of pH in the reaction wells of this platform. We have demonstrated very efficient nitration of tyrosine by peroxynitrite at different pH values and with varying concentrations of carbonate. In addition to tyrosine, a set of tyrosine-containing peptides was also studied. Presence of glutathione in the reaction wells increases the extent of tyrosine nitration in such peptide substrates presumably by raising the lifetime of nitric oxide in the reaction medium. When a cysteine residue was included in the sequence of the peptide, the extent of nitration of the tyrosine residue was found to depend on the position of the cysteine residue with respect to tyrosine. The extent of tyrosine nitration is strongly attenuated when the cysteine residue is directly adjacent to the tyrosine. This effect has been attributed to an intramolecular radical transfer mechanism. Taken together, results of this study demonstrate the potential of this light-controlled platform as a convenient bioanalytical tool in studying the reactions of peroxynitrite under widely varying conditions.
      Graphical abstract image

      PubDate: 2014-05-09T21:28:27Z
       
  • The cytotoxicity of the anticancer drug elesclomol is due to oxidative
           stress indirectly mediated through its complex with Cu(II)
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Brian B. Hasinoff , Arun A. Yadav , Daywin Patel , Xing Wu
      Elesclomol is an anticancer drug that is currently undergoing clinical trials. Elesclomol forms a strong 1:1 complex with Cu(II) and may exert its anticancer activity through the induction of oxidative stress and/or its ability to transport copper into the cell. A UV–vis spectrophotometric titration showed that Cu(I) also formed a 1:1 complex with elesclomol. Ascorbic acid, but not glutathione or NADH, potently reduced the Cu(II)-elesclomol complex to produce hydrogen peroxide. Even though hydrogen peroxide mediated reoxidation of the copper(I) produced by ascorbic acid reduction has the potential to lead to hydroxyl radical formation, electron paramagnetic resonance spin trapping experiments, either with or without added hydrogen peroxide, showed that the ascorbic acid-reduced Cu(II)-elesclomol complex could not directly generate damaging hydroxyl radicals. Both Cu(II)-elesclomol and elesclomol potently oxidized dichlorofluorescin in K562 cells. The highly specific copper chelators tetrathiomolybdate and triethylenetetramine were found to greatly reduce the cytotoxicity of both elesclomol and Cu(II)-elesclomol complex towards erythroleukemic K562 cells, consistent with a role for copper in the cytotoxicity of elesclomol. The superoxide dismutating activity of Cu(II)-elesclomol was much lower than that of Cu(II). Depletion of glutathione levels in K562 cells by treatment with buthionine sulfoximine sensitized cells to both elesclomol and Cu(II)-elesclomol. In conclusion, these results showed that elesclomol indirectly inhibited cancer cell growth through Cu(II)-mediated oxidative stress.
      Graphical abstract image

      PubDate: 2014-05-05T06:17:40Z
       
  • Enhanced anti-cancer efficacy to cancer cells by doxorubicin loaded
           water-soluble amino acid-modified β-cyclodextrin platinum complexes
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Mei-Xia Zhao , Meng Zhao , Er-Zao Zeng , Yang Li , Jin-Ming Li , Qian Cao , Cai-Ping Tan , Liang-Nian Ji , Zong-Wan Mao
      The effective targeted delivery of insoluble anticancer drugs to increase the intracellular drug concentration has become a focus in cancer therapy. In this system, two water-soluble amino acid-modified β-cyclodextrin (β-CD) platinum complexes were reported. They showed preferable binding ability to DNA and effective inhibition to cancer cells, and they could bind and unwind pBR322 DNA in a manner which was similar to cisplatin. Besides, our platinum complexes could effectively deliver the anticancer drug doxorubicin (Dox) into cells and had higher cell inhibition ratio, but less toxicity on the normal cells, compared with cancer cells. In this combination system, Dox was encapsulated into the hydrophobic cavities of β-CD at the optimum molar ratio of 1:1, which were validated by UV–visible (UV–vis) absorption spectroscopy, fluorescence spectroscopy and MTT experiments. Moreover, the combination system had higher cell inhibition ratio than free Dox and amino acid-modified β-CD platinum complexes, and the results of high content screening (HCS) showed that Dox-loaded amino acid-modified β-CD platinum complexes could permeate the cell membrane and enter cells, suggesting the efficient transport of Dox across the membranes with the aid of the β-CD. We expect that the amino acid-modified β-CD platinum complexes will deliver the antitumor drug Dox to enhance intracellular drug accumulation and such combination system showed great potential as an antitumor drug.
      Graphical abstract image

      PubDate: 2014-05-05T06:17:40Z
       
  • A platinum(II) complex of liriodenine from traditional Chinese medicine
           (TCM): Cell cycle arrest, cell apoptosis induction and telomerase
           inhibition activity via G-quadruplex DNA stabilization
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Yu-Lan Li , Qi-Pin Qin , Yan-Cheng Liu , Zhen-Feng Chen , Hong Liang
      Liriodenine (L), an antitumor active ingredient from the traditional Chinese medicine (TCM), Zanthoxylum nitidum, afforded a platinum(II) complex (1) of L, cis-[PtCl2(L)(DMSO)], which previously reported for its in vitro antitumor activity and intercalative binding with DNA. In this study, complex 1 was further discussed for its antitumor mechanism and structure–activity relationship, comparing with L and cisplatin. Towards the most sensitive BEL-7404 human hepatoma cells, complex 1 significantly induced cell cycle arrest at both G2/M phase and S phase. It suggests that double helix DNA is not the simplex intracellular target for 1. On the other hand, the BEL-7404 cells incubated with 1 and stained by Hoechst 33258 and AO/EB showed typical cell apoptosis in dose-dependent manner. The BEL-7404 cells incubated with 1 and stained by JC-1 were also characteristic for cell apoptosis on the loss of mitochondrial membrane potential. Furthermore, the G-quadruplex DNA binding property of complex 1 was also investigated by spectroscopic analyses, fluorescent indicator displacement (FID) assay and fluorescence resonance energy transfer (FRET) assay. The results indicated that 1 stabilized the human telomeric G4-HTG21 DNA better than L. The telomerase inhibition ratio of 1 ((62.50±0.03)%), which was examined by telomerase polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), was much higher than L ((21.77±0.01)%). It can be ascribed to the better G4-HTG21 DNA stabilization of 1 than L. The results suggested that the nuclei, mitochondria and telomerase via G-quadruplex DNA stabilization all should be key targets for the antitumor mechanism of 1, in which the central platinum(II) played a key role.
      Graphical abstract image

      PubDate: 2014-05-05T06:17:40Z
       
  • Synthesis, characterization, crystal structures and biological activity of
           set of Cu(II) benzothiazole complexes: Artificial nucleases with cytotoxic
           activities
    • Abstract: Publication date: August 2014
      Source:Journal of Inorganic Biochemistry, Volume 137
      Author(s): Ramsey A. Steiner , David Foreman , Han X. Lin , Bruce K. Carney , Kristin M. Fox , Lynne Cassimeris , Joseph M. Tanski , Laurie A. Tyler
      A series of Cu(II) complexes with ligand frames based on quinoline derivatives appended with a benzothiazole substituent has been isolated. The complexes, Cu(Q(oBt))(NO3)2(H2O)∙CH3OH (1 ∙CH3OH), Cu(8OHQ(oBt))Cl2 ∙CH3OH (2 ∙CH3OH), Cu(8OQ(oBt))Cl(CH3OH)∙CH3OH (3 ∙CH3OH) and [Cu(8OH1/2Q(oBt))(CH3OH)(NO3)]2(NO3) (4) have been characterized by single crystal X-ray diffraction, IR and UV-visible spectroscopies, and elemental analysis. The ligand frame within the set of complexes differs in the substituent on the quinoline ring: complex 1 remains unsubstituted at this position while complexes 2–4 have a substituted OH group. In complex 2, the bound phenol remains protonated while in 3 it is a phenolato group. Complex 4 contains two complexes within the unit cell and one NO3 − giving rise to an overall ‘half-protonation’. The interaction between complexes 1–3 with CT-DNA was investigated using fluorescence emission spectroscopy and revealed 2 and 3 strongly intercalate DNA with Kapp values of 1.47×107 M−1 and 3.09×107 M−1, respectively. The ability of complexes 1–3 to cleave SC-DNA was monitored using gel electrophoresis. Each complex exhibits potent, concentration dependent nuclease activity forming single and double-nicked DNA as low as 10μM. The nuclease activity of complexes 1–3 is primarily dependent on 1O2 species while ·OH radicals play a secondary role in the cleavage by complexes 2 and 3. The cytotoxic effects of 1–3 were examined using HeLa cells and show cell death in the micromolar range. The distribution of cell cycle stages remains unchanged when complexes are present indicating DNA damage may be occurring throughout the cell cycle.
      Graphical abstract image

      PubDate: 2014-05-05T06:17:40Z
       
  • Inductively coupled plasma mass spectrometry for metallodrug development:
           Albumin binding and serum distribution of cytotoxic cis- and
           trans-isomeric platinum(II) complexes
    • Abstract: Publication date: Available online 22 April 2014
      Source:Journal of Inorganic Biochemistry
      Author(s): Konstantin Ossipov , Yulia Y. Scaffidi-Domianello , Irina F. Seregina , Markus Galanski , Bernhard K. Keppler , Andrei R. Timerbaev , Mikhail A. Bolshov
      Binding to plasma proteins is one of the major metabolic pathways of metallodrugs. In the case of platinum-based anticancer drugs, it is interaction with serum albumin that affects most strongly their in vivo behavior. Since both the configuration, i.e. cis-trans-isomerism, and the nature of leaving groups have an effect on the reactivity of Pt(II) coordination compounds toward biomolecules, a set of cis- and trans-configured complexes with halide leaving groups (Cl–, Br–, and I–) and 2-propanone oxime as carrier ligands was chosen for this study. Binding experiments were performed both with albumin and human serum and the Pt content in ultrafiltrates was quantified using inductively coupled plasma mass spectrometry. In order to shed light on the binding mechanism, the albumin binding constant (K HSA) and the octanol–water partition coefficient (P) were experimentally determined and relationships between log K HSA and log P were explored. The correlation was found significant only for cis-configured platinum complexes (R 2 =0.997 and standard deviation=0.02), indicating a certain contribution of the nonspecific binding which is largely dominated by the lipophilicity of compounds. In contrast, for trans-complexes a specific molecular recognition element plays a significant role. The participation of albumin in drug distribution in blood serum was assessed using an equilibrium distribution model and by comparing the percentage binding in the albumin and serum-protein fractions. Irrespective of the compound polarity, albumin contributes from 85 to 100% to the overall binding in serum.
      Graphical abstract image

      PubDate: 2014-04-26T06:16:12Z
       
 
 
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