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  Subjects -> CHEMISTRY (Total: 849 journals)
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INORGANIC CHEMISTRY (41 journals)

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Acta Polymerica     Hybrid Journal   (Followers: 9)
Additives for Polymers     Full-text available via subscription   (Followers: 20)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 9)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 3)
Bioinorganic Chemistry and Applications     Open Access   (Followers: 9)
Comments on Inorganic Chemistry: A Journal of Critical Discussion of the Current Literature     Hybrid Journal   (Followers: 1)
Current Methods in Inorganic Chemistry     Full-text available via subscription   (Followers: 2)
European Journal of Inorganic Chemistry     Hybrid Journal   (Followers: 11)
European Polymer Journal     Hybrid Journal   (Followers: 41)
Heterocyclic Communications     Hybrid Journal  
High Performance Polymers     Hybrid Journal   (Followers: 1)
Indian Journal of Chemistry - Section A     Open Access   (Followers: 7)
Inorganic Chemistry     Full-text available via subscription   (Followers: 23)
Inorganic Chemistry Communications     Hybrid Journal   (Followers: 10)
Inorganic Chemistry Frontiers     Full-text available via subscription   (Followers: 3)
Inorganic Materials     Hybrid Journal   (Followers: 3)
Inorganic Materials: Applied Research     Hybrid Journal   (Followers: 1)
Inorganica Chimica Acta     Hybrid Journal   (Followers: 6)
Inorganics     Open Access  
International Journal of Bio-Inorganic Hybrid Nanomaterials     Open Access   (Followers: 1)
International Journal of Inorganic Chemistry     Open Access   (Followers: 2)
JBIC Journal of Biological Inorganic Chemistry     Hybrid Journal   (Followers: 5)
Journal of Inorganic and Organometallic Polymers and Materials     Partially Free   (Followers: 8)
Journal of Inorganic Biochemistry     Hybrid Journal   (Followers: 6)
Journal of Polymer Engineering     Hybrid Journal   (Followers: 9)
Journal of Polymers and the Environment     Hybrid Journal   (Followers: 1)
Journal of Separation Science     Hybrid Journal   (Followers: 11)
Metallodrugs     Open Access   (Followers: 1)
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: 15)
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: 2)
Topics in Inorganic and General Chemistry     Full-text available via subscription  
Zeitschrift für anorganische und allgemeine Chemie     Hybrid Journal   (Followers: 2)
Zeitschrift für Kristallographie - New Crystal Structures     Open Access  
Journal Cover Journal of Inorganic Biochemistry
  [SJR: 0.983]   [H-I: 100]   [6 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0162-0134
   Published by Elsevier Homepage  [3039 journals]
  • Water-soluble metalloporphyrinates with excellent photo-induced anticancer
           activity resulting from high tumor accumulation
    • Authors: Xiaojun Hu; Kazuma Ogawa; Tatsuto Kiwada; Akira Odani
      Pages: 1 - 7
      Abstract: Publication date: May 2017
      Source:Journal of Inorganic Biochemistry, Volume 170
      Author(s): Xiaojun Hu, Kazuma Ogawa, Tatsuto Kiwada, Akira Odani
      To develop a water-soluble and tumor-targeted photosensitizer for photodynamic therapy (PDT), a porphyrin framework containing the metal ion gallium(III) was combined with platinum(II)-based groups to produce two new pentacationic metalloporphyrinates, Ga-4cisPtTPyP (5,10,15,20-tetrakis{cis-diammine-chloro-platinum(II)}(4-pyridyl)-porphyrinato gallium(III) hydroxide tetranitrate) and Ga-4transPtTPyP (5,10,15,20-tetrakis{trans-diammine-chloro-platinum(II)} (4-pyridyl)-porphyrinato gallium(III) hydroxide tetranitrate). Both complexes exhibited high singlet oxygen quantum yields (Φ∆) and remarkable photocytotoxicity with appreciable phototoxic indexes (PIs). In particular, Ga-4cisPtTPyP showed a low IC50 value (Colon 26: 0.12μM; Sarcoma 180: 0.08μM) under illumination and its PI up to 1000. With outstanding tumor accumulation (tumor/muscle ratio>9), Ga-4cisPtTPyP almost completely inhibited tumor growth over two weeks in an in vivo PDT assay. These results imply that Ga-4cisPtTPyP could be a promising anticancer agent for use in PDT.
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      PubDate: 2017-02-09T11:16:19Z
      DOI: 10.1016/j.jinorgbio.2017.02.001
      Issue No: Vol. 170 (2017)
       
  • The dissociation of the Hsp60/pro-Caspase-3 complex by
           bis(pyridyl)oxadiazole copper complex (CubipyOXA) leads to cell death in
           NCI-H292 cancer cells
    • Authors: Celeste Caruso Bavisotto; Dragana Nikolic; Antonella Marino Gammazza; Rosario Barone; Filippa Lo Cascio; Emanuele Mocciaro; Giovanni Zummo; Everly Conway de Macario; Alberto JL Macario; Francesco Cappello; Valentina Giacalone; Andrea Pace; Giampaolo Barone; Antonio Palumbo Piccionello; Claudia Campanella
      Pages: 8 - 16
      Abstract: Publication date: May 2017
      Source:Journal of Inorganic Biochemistry, Volume 170
      Author(s): Celeste Caruso Bavisotto, Dragana Nikolic, Antonella Marino Gammazza, Rosario Barone, Filippa Lo Cascio, Emanuele Mocciaro, Giovanni Zummo, Everly Conway de Macario, Alberto JL Macario, Francesco Cappello, Valentina Giacalone, Andrea Pace, Giampaolo Barone, Antonio Palumbo Piccionello, Claudia Campanella
      Cell survival and proliferation are central to carcinogenesis, involving various mechanisms among which those that impede apoptosis are important. In this, the role of the molecular chaperone Hsp60 is unclear since it has been reported that it can be both, pro- or anti-apoptotic. A solution to this riddle is crucial to the development of anti-cancer therapies targeting Hsp60. We addressed this question using a tumor cell line, NCI-H292, and [Cu(3,5-bis(2′-pyridyl)-1,2,4-oxadiazole)2(H2O)2](ClO4)2, CubipyOXA, a copper-containing compound with cytotoxic properties. We treated cells with various doses of the compound and measured cell viability; apoptosis indicators; and levels of Hsp60, pro-Caspase-3 (pC3), Caspase-3 (C3), and complex Hsp60/pC3, with complementary methods. The quantitative dose-response curves of the levels of Hsp60, activated C3, inactivated pC3, Hsp60/pC3 complex and indicators of cell apoptosis, and cell death, all coincided to show that CubipyOXA has pro-apoptotic activity and promotes cell death. The curves also indicate that the pro-apoptotic effects of CubipyOXA could likely be due to a lowering of Hsp60 levels and to its blocking the formation of the Hsp60/pC3 complex and/or its dissociating the complex when already formed, thus, interfering with the anti-apoptotic action of Hsp60. These findings shed some light on how a tumor cell may avert apoptosis using Hsp60 and point to the anti-cancer potential of drugs, such as CubipyOXA, which interfere with Hsp60/pC3 complex formation, and thus allow the apoptotic cascade to proceed. In view of these findings it becomes clear that the novel compound CubipyOXA should be considered a potential, high-efficiency antitumor agent deserving further testing.
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      PubDate: 2017-02-15T11:26:58Z
      DOI: 10.1016/j.jinorgbio.2017.02.004
      Issue No: Vol. 170 (2017)
       
  • New 4′-(4-chlorophenyl)-2,2′:6′,2″-terpyridine ruthenium(II)
           complexes: Synthesis, characterization, interaction with DNA/BSA and
           cytotoxicity studies
    • Authors: Milan M. Milutinović; Ana Rilak; Ioannis Bratsos; Olivera Klisurić; Milan Vraneš; Nevenka Gligorijević; Siniša Radulović; Živadin D. Bugarčić
      Pages: 1 - 12
      Abstract: Publication date: April 2017
      Source:Journal of Inorganic Biochemistry, Volume 169
      Author(s): Milan M. Milutinović, Ana Rilak, Ioannis Bratsos, Olivera Klisurić, Milan Vraneš, Nevenka Gligorijević, Siniša Radulović, Živadin D. Bugarčić
      In this study, we have developed a series of new monofunctional Ru(II) complexes of the general formula mer-[Ru(Cl-Ph-tpy)(N-N)Cl]Cl in which Cl-Ph-tpy is 4′-(4-chlorophenyl)-2,2′:6′,2″-terpyridine, N-N is a bidentate chelating ligand (1,2-diaminoethane (en, 1), 1,2-diaminocyclohexane (dach, 2) or 2,2′-bipyridine (bpy, 3)). All complexes were fully characterized by elemental analysis and spectroscopic techniques (IR, UV–Vis, 1D and 2D NMR). Their chemical behavior in aqueous solution was studied by UV–Vis and NMR spectroscopy showing that all compounds are relatively labile leading to the formation of the corresponding aqua species 1aq–3aq. Their DNA binding ability was evaluated by UV–Vis spectroscopy, fluorescence quenching measurements and viscosity measurements. Competitive studies with ethidium bromide (EB) showed that the complexes can displace DNA-bound EB, suggesting strong competition with EB (K sv =1.1–2.7×104 M−1). These experiments show that the ruthenium complexes interact with DNA via intercalation. The complexes bind to serum protein albumin displaying relatively high binding constants (K sv =104–105 M−1). Compound 3 displayed from high to moderate cytotoxicity against two cancer cell lines HeLa and A549 (with IC50 ca. 12.7μM and 53.8μM, respectively), while complexes 1 and 2 showed only moderate cytotoxicity (with IC50 ca. 84.8μM and 96.3μM, respectively) against HeLa cells. The cell cycle analysis (by flow cytometry) of HeLa and A549 cells treated with complex 3 shows minor changes on the cell cycle phase distribution.
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      PubDate: 2017-01-13T22:45:42Z
      DOI: 10.1016/j.jinorgbio.2016.10.001
      Issue No: Vol. 169 (2017)
       
  • Heterologous expression of Halomonas halodenitrificans nitric oxide
           
    • Authors: Nobuhiko Sakurai; Kunishige Kataoka; Noriko Sugaya; Takaki Shimodaira; Mie Iwamoto; Munehiro Shoda; Hajime Horiuchi; Miyuki Kiyono; Yasuke Ohta; Bambang Triwiyono; Daisuke Seo; Takeshi Sakurai
      Pages: 61 - 67
      Abstract: Publication date: April 2017
      Source:Journal of Inorganic Biochemistry, Volume 169
      Author(s): Nobuhiko Sakurai, Kunishige Kataoka, Noriko Sugaya, Takaki Shimodaira, Mie Iwamoto, Munehiro Shoda, Hajime Horiuchi, Miyuki Kiyono, Yasuke Ohta, Bambang Triwiyono, Daisuke Seo, Takeshi Sakurai
      Halomonas halodenitrificans nitric oxide reductase (NOR) is the membrane-bound heterodimer complex of NorC, which contains a low-spin heme c center, and NorB, which contains a low-spin heme b center, a high-spin heme b 3 center, and a non-heme FeB center. The soluble domain of NorC, NorC* (ΔMet1–Val37) was heterologously expressed in Escherichia coli using expression plasmids harboring the truncated norC gene deleted of its 84 5′-terminal nucleotides. Analogous scission of the N-terminal helix as the membrane anchor took place when the whole norC gene was used. NorC* exhibited spectra typical of a low-spin heme c. In addition, NorC* functioned as the acceptor of an electron from a cytochrome c isolated from the periplasm of H. halodenitrificans and small reducing reagents. The redox potential of NorC* shifted ca. 40mV in the negative direction from that of NorC. Unlike NorC, recombinant NorB was not heterologously expressed. However, recombinant NOR (rNOR) could be expressed in E. coli by using a plasmid harboring all genes in the nor operon, norCBQDX, from which the three hairpin loops (mRNA) were deleted, and by using the ccm genes for the maturation of C-type heme. rNOR exhibited the same spectroscopic properties and reactivity to NO and O2 as NOR, although its enzymatic activity toward NO was considerably decreased. These results on the expression of rNOR and NorC* will allow us to develop more profound studies on the properties of the four Fe centers and the reaction mechanism of NOR from this halophilic denitrifying bacterium.
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      PubDate: 2017-01-28T01:05:19Z
      DOI: 10.1016/j.jinorgbio.2017.01.006
      Issue No: Vol. 169 (2017)
       
  • New copper(I) and heteronuclear copper(I)–ruthenium(II) complexes:
           Synthesis, structural characterization and cytotoxicity
    • Authors: João Lopes; David Alves; Tânia S. Morais; Paulo J. Costa; M. Fátima M. Piedade; Fernanda Marques; Maria J. Villa de Brito; M. Helena Garcia
      Pages: 68 - 78
      Abstract: Publication date: Available online 23 January 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): João Lopes, David Alves, Tânia S. Morais, Paulo J. Costa, M. Fátima M. Piedade, Fernanda Marques, Maria J. Villa de Brito, M. Helena Garcia
      A new family of copper(I) complexes of general formula [Cu(dppe)(NN)]+ have been synthesized and fully characterized, with dppe=1.2-bis(diphenylphosphino)ethane and NN representing several bidentate heteroaromatic ligands: 2,2′-bipy=2.2′-bipyridine (1), Me2bpy=4.4′-dimethyl-2,2′-bipyridine (2), dpytz=3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine (3), dpp=2.3-bis(2-pyridyl)pyrazine (4), and the metallaligand [Ru(η5-C5H5)(PPh3)(dpp)]+ (5), yielding the bimetallic copper(I)-ruthenium(II) complex [Cu(dppe)(μ-dpp)Ru(η5-C5H5)(PPh3)]2+ (6). The single crystal structures of complexes (2) and (4) were determined by X-ray diffraction studies. All the complexes exhibit high cytotoxicity against the human cancer cells A2780 and MCF7 far lower than those found for the antitumor drug cisplatin in the same cell lines and even surpassing cisplatin resistance in the A2780cisR cells. They display IC50 values on the human embryonic kidney HEK293 non-tumoral cells of the same order of magnitude as those found for the tumoral cells. In the ovarian cells the compounds induce rapid production of reactive oxygen species (ROS) probably through mitochondrial pathways. According to the results reported here, these compounds can be considered as prospective antitumoral agents that deserve further evaluation.
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      PubDate: 2017-01-28T01:05:19Z
      DOI: 10.1016/j.jinorgbio.2017.01.007
      Issue No: Vol. 169 (2017)
       
  • Influence of components of tumour microenvironment on the response of
           HCT-116 colorectal cancer to the ruthenium-based drug NAMI-A
    • Authors: Alberta Bergamo; Chiara Pelillo; Angela Chambery; Gianni Sava
      Pages: 90 - 97
      Abstract: Publication date: March 2017
      Source:Journal of Inorganic Biochemistry, Volume 168
      Author(s): Alberta Bergamo, Chiara Pelillo, Angela Chambery, Gianni Sava
      Solid tumours are constituted of tumour cells, healthy cells recruited from the host tissues and soluble factors released by both these cell types. The present investigation examines the capacity of co-cultures between the HCEC colon epithelial cells and the HCT-116 colorectal cancer cells (mimicking the primary site of tumour growth) and between IHH hepatocytes and the HCT-116 colorectal cancer cells (metastatic site) to influence the effects of NAMI-A (imidazolium trans-imidazoledimethylsulphoxidetetrachloro ruthenate) on the tumour cells themselves. The growth of HCT-116 cells is significantly influenced when the cancer cells are sown on a monolayer of HCEC. The release of soluble factors by the healthy cells promotes, in HCT-116 colorectal cancer cells, the transcription of genes involved in growth, invasion and migration. NAMI-A is not cytotoxic to HCT-116 cells grown on plastics or co-cultured with HCEC or IHH cells, and maintains its ability to control the cell pseudo-metastatic ability, mimicked by the migration in the scratch test. The effects of NAMI-A on HCT-116 migration are supported by its inhibition of the transcription of the ABL-2, ATF-3 and RND-1 genes. In conclusion the study highlights the need of test systems more complex than a single cancer cell culture to study an anticancer drug in vitro and reinforces the hypothesis that NAMI-A targets the ability of the cancer cell to interact with the tumour microenvironment and with the signals that support its metastatic ability.
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      PubDate: 2017-01-05T22:15:30Z
      DOI: 10.1016/j.jinorgbio.2016.11.031
      Issue No: Vol. 168 (2017)
       
  • Synthesis, spectral characterization of novel Pd(II), Pt(II)
           π-coordination compounds based on N-allylthioureas. Cytotoxic properties
           and DNA binding ability
    • Authors: H.H. Repich; V.V. Orysyk; L.G. Palchykovska; S.I. Orysyk; Yu. L. Zborovskii; O.V. Vasylchenko; O.V. Storozhuk; A.A. Biluk; V.V. Nikulina; L.V. Garmanchuk; V.I. Pekhnyo; M.V. Vovk
      Pages: 98 - 106
      Abstract: Publication date: March 2017
      Source:Journal of Inorganic Biochemistry, Volume 168
      Author(s): H.H. Repich, V.V. Orysyk, L.G. Palchykovska, S.I. Orysyk, Yu. L. Zborovskii, O.V. Vasylchenko, O.V. Storozhuk, A.A. Biluk, V.V. Nikulina, L.V. Garmanchuk, V.I. Pekhnyo, M.V. Vovk
      Four novel Pd2+ and Pt2+ mononuclear π-coordination compounds with general formula [M(HL)1,2Cl2], M=Pd2+, Pt2+ have been synthesized by reaction of [PdCl4]2−, [PtCl4]2− anions with N-allyl-4-morpholinethiocarboxamide (HL1) and N-Allyl-N'-tert-butylthiourea (HL2). All complexes have been characterized by single-crystal X-ray diffraction study and 1H, 13C NMR spectroscopy. Cytotoxic, cytostatic and proapoptotic activities of compounds have been determined in vitro on HeLa cell line and compared with cisplatin as etalon drug. All complex compounds possessed pronounced cytotoxic activity with IC50 indexes in range of 2·10−6–1.5·10−4 М (IC50 of cisplatin is 5.7∙10−5 М) and showed proapoptotic, cytostatic and antisyntetic influence higher or comparable with cisplatin. The comparative influence of cisplatin and synthesized metal complexes on pTZ19R* plasmid DNA was monitored by agarose gel electrophoresis. All compounds showed high affinity to DNA that correlates with observed cytostatic and proapoptotic levels. In general Pd(II) compounds showed higher activity than Pt(II) ones.
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      PubDate: 2017-01-13T22:45:42Z
      DOI: 10.1016/j.jinorgbio.2016.12.004
      Issue No: Vol. 168 (2017)
       
  • Citrate and albumin facilitate transferrin iron loading in the presence of
           phosphate
    • Authors: Catalina Matias; Devin W. Belnap; Michael T. Smith; Michael G. Stewart; Isaac F. Torres; Andrew J. Gross; Richard K. Watt
      Pages: 107 - 113
      Abstract: Publication date: March 2017
      Source:Journal of Inorganic Biochemistry, Volume 168
      Author(s): Catalina Matias, Devin W. Belnap, Michael T. Smith, Michael G. Stewart, Isaac F. Torres, Andrew J. Gross, Richard K. Watt
      Labile plasma iron (LPI) is redox active, exchangeable iron that catalyzes the formation of reactive oxygen species. Serum transferrin binds iron in a non-exchangeable form and delivers iron to cells. In several inflammatory diseases serum LPI increases but the reason LPI forms is unknown. This work evaluates possible pathways leading to LPI and examines potential mediators of apo transferrin iron loading to prevent LPI. Previously phosphate was shown to inhibit iron loading into apo transferrin by competitively binding free Fe3+. The reaction of Fe3+ with phosphate produced a soluble ferric phosphate complex. In this study we evaluate iron loading into transferrin under physiologically relevant phosphate conditions to evaluate the roles of citrate and albumin in mediating iron delivery into apo transferrin. We report that preformed Fe3+-citrate was loaded into apo transferrin and was not inhibited by phosphate. A competition study evaluated reactions when Fe3+ was added to a solution with citrate, phosphate and apo transferrin. The results showed citrate marginally improved the delivery of Fe3+ to apo transferrin. Studies adding Fe3+ to a solution with phosphate, albumin and apo transferrin showed that albumin improved Fe3+ loading into apo transferrin. The most efficient Fe3+ loading into apo transferrin in a phosphate solution occurred when both citrate and albumin were present at physiological concentrations. Citrate and albumin overcame phosphate inhibition and loaded apo transferrin equal to the control of Fe3+ added to apo transferrin. Our results suggest a physiologically important role for albumin and citrate for apo transferrin iron loading.
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      PubDate: 2017-01-21T00:34:02Z
      DOI: 10.1016/j.jinorgbio.2016.12.010
      Issue No: Vol. 168 (2017)
       
  • Siderophore transport by MmpL5-MmpS5 protein complex in Mycobacterium
           tuberculosis
    • Authors: Padmani Sandhu; Yusuf Akhter
      Abstract: Publication date: Available online 14 February 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Padmani Sandhu, Yusuf Akhter
      Iron is an essential metal ion required for the various physiological activities of bacteria. The pathogenic bacteria remain dependent on the host cell for their iron requirements and evolved with specialized scavenging machinery in the form of iron chelating siderophores. Mycobacterium tuberculosis (Mtb) has two types of siderophore molecules, mycobactin and carboxymycobactin. These are synthesized inside bacterial cell and need to be transported outside by specialized membrane associated proteins. MmpL5-MmpS5 protein complex has been linked to the export of non-ferrated siderophores to extracellular environment but the precise molecular mechanism involved was largely unknown. We have investigated the association of MmpL5 with mycobactin synthesis and transport associated proteins using system wide protein-protein interaction network. Insights of mycobactin transport mechanism by MmpL5-MmpS5 complex was explored using docking and molecular dynamics simulations. The MmpL5 have association with many proteins which have reported role in iron acquisition or mycobactin biosynthesis. Mycobactin was docked into cytoplasmic and periplasmic binding sites. The molecular dynamics simulation analysis showed that at cytoplasmic binding site mycobactin could move towards the central channel of efflux pump and at periplasmic binding site towards the periplasm. MmpL5 was observed to carry out uptake of mycobactin from the cytoplasm and its release into the periplasmic space and MmpS5 was found to facilitate the periplasmic release of mycobactin and enhance the transport function of MmpL5. The mycobactin export is an attractive target for drug discovery and it could be done by inhibiting the MmpL5 protein's transport function.
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      PubDate: 2017-02-15T11:26:58Z
      DOI: 10.1016/j.jinorgbio.2017.02.013
       
  • Proteome scale identification, classification and structural analysis of
           iron-binding proteins in bread wheat
    • Authors: Shailender Kumar Verma; Ankita Sharma; Padmani Sandhu; Neha Choudhary; Shailaja Sharma; Vishal Acharya; Yusuf Akhter
      Abstract: Publication date: Available online 14 February 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Shailender Kumar Verma, Ankita Sharma, Padmani Sandhu, Neha Choudhary, Shailaja Sharma, Vishal Acharya, Yusuf Akhter
      Bread wheat is one of the major staple foods of worldwide population and iron plays a significant role in growth and development of the plant. In this report, we are presenting the genome wide identification of iron-binding proteins in bread wheat. In the present study, the wheat genome derived putative proteome was screened for identification of iron-binding sequence motifs. Out of 602 putative iron-binding proteins, 130 were able to produce reliable structural models by homology techniques and further analyzed for the presence of iron-binding structural motifs. The computationally identified proteins appear to bind to ferrous and ferric ions and showed diverse coordination geometries. Glu, His, Asp and Cys amino acid residues were found to be mostly involved in iron binding. We have classified these proteins on the basis of their localization in the different cellular compartments. The identified proteins were further classified into their protein folds, families and functional classes ranging from structure maintenance of cellular components, regulation of gene expression, post translational modification, membrane proteins, enzymes, signaling and storage proteins. This comprehensive report regarding structural iron binding proteome provides useful insights into the diversity of iron binding proteins of wheat plants and further utilized to study their roles in plant growth, development and physiology.
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      PubDate: 2017-02-15T11:26:58Z
      DOI: 10.1016/j.jinorgbio.2017.02.012
       
  • EPR and photophysical characterization of six bioactive oxidovanadium(IV)
           complexes in the conditions of in vitro cell tests
    • Authors: Marta Lovisari; Giorgio Volpi; Domenica Marabello; Silvano Cadamuro; Annamaria Deagostino; Eliano Diana; Alessandro Barge; Margherita Gallicchio; Valentina Boscaro; Elena Ghibaudi
      Abstract: Publication date: Available online 13 February 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Marta Lovisari, Giorgio Volpi, Domenica Marabello, Silvano Cadamuro, Annamaria Deagostino, Eliano Diana, Alessandro Barge, Margherita Gallicchio, Valentina Boscaro, Elena Ghibaudi
      A number of oxidovanadium(IV) complexes have been reported to display anticancer activity. A theranostic approach, based on the simultaneous observation of both the effect of oxidovanadium(IV) complexes on cell viability and the disclosure of their intracellular fate, is possible by using oxidovanadium(IV) complexes functionalized with fluorescent ligands. In the present study we accomplished the characterization of six oxidovanadium(IV) complexes in conditions close to those employed for in vitro administration. In particular, we investigated the light harvesting properties of such complexes in the presence of a dimethylsulphoxide/aqueous buffer mixture, and we found that one complex exhibits a quantum yield suitable for confocal microscopy investigations. EPR investigations in the same conditions provide information about the presence of ligands' substitution processes. Finally, the electrochemical properties of all complexes were determined by cyclic voltammetry. The overall results show that these complexes exhibit an average stability in solution; EPR data confirm that DMSO enter the first coordination sphere of oxidovanadium(IV) and suggest the occurrence of partial ligand substitution in the dimethylsulphoxide/aqueous buffer mixture.
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      PubDate: 2017-02-15T11:26:58Z
      DOI: 10.1016/j.jinorgbio.2017.02.009
       
  • Disaggregation of human islet amyloid polypeptide fibril formation by
           ruthenium polypyridyl complexes
    • Authors: Dengsen Zhu; Gehui Gong; Wenji Wang; Weihong Du
      Abstract: Publication date: Available online 13 February 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Dengsen Zhu, Gehui Gong, Wenji Wang, Weihong Du
      The toxicity of amyloid proteins is associated with many degenerative and systematic diseases. The aggregation of human islet amyloid polypeptide may induce pancreatic β-cell death, which is linked to type II diabetes. Ruthenium complexes are inhibitors of various proteins and potential anticancer metallodrugs, which can also be used to disaggregate amyloid proteins. This work reported that several ruthenium polypyridyl complexes remarkably affected the peptide aggregation by predominant hydrophobic interaction and metal coordination, as reflected by thermodynamic parameters and mass spectrometry analysis. Morphology and particle size analysis showed that the amyloid fibrils were disaggregated from long fibrils into small nano particles. Addition of these complexes also decreased the cytotoxicity induced by the peptide. The results indicated that ruthenium polypyridyl complexes may be potential metallodrugs to treat amyloidosis.
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      PubDate: 2017-02-15T11:26:58Z
      DOI: 10.1016/j.jinorgbio.2017.02.008
       
  • Structural and functional insights into corrinoid iron-sulfur protein from
           human pathogen Clostridium difficile
    • Authors: Yaozhu Wei; Xiaofei Zhu; Sixue Zhang; Xiangshi Tan
      Abstract: Publication date: Available online 13 February 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Yaozhu Wei, Xiaofei Zhu, Sixue Zhang, Xiangshi Tan
      The human pathogen Clostridium difficile infection (CDI) is one of the most important healthcare-associated infections. The Wood-Ljungdahl pathway, which is responsible for Acetyl-CoA biosynthesis, is essential for the survival of the pathogen and is absent in humans. The key proteins and enzymes involved in the pathway are attractive targets for the treatment of CDI. Corrinoid iron-sulfur protein (CoFeSP) is a key protein and acts as a methyl transformer in the Wood-Ljungdahl pathway. In this study, CoFeSP from Clostridium difficile (CoFeSPCd) was cloned, expressed in E. coli and characterized for the first time. The structure and function of CoFeSPCd were investigated using homology structure modeling, spectroscopy, electrochemistry, steady state/pre-steady state kinetics and molecular docking. The two metal centers of CoFeSPCd, corrinoid cofactor and [4Fe-4S] cluster, were characterized using metal analysis, structural modeling, UV–Vis, EPR and direct electrochemistry. The methyl transfer activity between CH3-H4folate (CH3-THF) and CoFeSPCd catalyzed by methyl transferase (MeTrCd) was determined by kinetic studies. These results provide a molecular basis for innovative drug design and development to treat human CDI.
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      PubDate: 2017-02-15T11:26:58Z
      DOI: 10.1016/j.jinorgbio.2017.02.005
       
  • New Pt-NNSO core anticancer agents: Structural optimization and
           investigation of their anticancer activity
    • Authors: Shu Xian Chong; Yinxue Jin; Steve Chik Fun Au-Yeung; Kenneth Kin Wah To
      Abstract: Publication date: Available online 12 February 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Shu Xian Chong, Yinxue Jin, Steve Chik Fun Au-Yeung, Kenneth Kin Wah To
      A series of new platinum Pt(II) compounds possessing a bidentate leaving ligand modified from oxaliplatin has been synthesized, with one of the oxygen ligating atom substituted for a sulphur atom (resulting in a Pt-NNSO coordination core structure). The general structures are R,R-diaminocyclohexane (DACH)-Pt-(methylthio)acetic acid (K4) and DACH-Pt-(thiophenylacetic acid) (K4 derivatives). Substitution of an electron donating or withdrawing group at the ortho or para position on the phenyl ring of K4 derivatives was found to affect the complexes' stability, reactivity with the biological molecules (5′-guanosine monophosphate (5′-GMP) and L-methionine (L-Met)) and anticancer activity. 1H NMR experiments demonstrated that Pt-NNSO complexes formed a mixture of mono- and diadduct with 5′-GMP in various ratios, which are different from the classical Pt drugs (forming mainly diadduct). In addition, all of the K4 derivatives with improved lipophilicity are less deactivated by L-Met in comparison to cisplatin (CDDP) and oxaliplatin. Biological assessments showed that all Pt-NNSO complexes are less toxic than CDDP in normal porcine kidney cells and are minimally affected by drug resistance. Some of the new compounds also displayed comparable anticancer activity to CDDP or better than carboplatin in a few cancer cell lines. The lower reactivity of the Pt-NNSO compounds than CDDP towards thiol molecules, presumably leading to less efflux in resistant cancer cells, and the ability to inhibit autophagy were believed to allow the new compounds to be less affected by Pt resistance.
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      PubDate: 2017-02-15T11:26:58Z
      DOI: 10.1016/j.jinorgbio.2017.02.002
       
  • Zinc complexes of diflunisal: Synthesis, characterization, structure,
           antioxidant activity, and in vitro and in silico study of the interaction
           with DNA and albumins
    • Authors: Alketa Tarushi; Chrisoula Kakoulidou; Catherine P. Raptopoulou; Vassilis Psycharis; Dimitris P. Kessissoglou; Ioanna Zoi; Athanasios N. Papadopoulos; George Psomas
      Abstract: Publication date: Available online 12 February 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Alketa Tarushi, Chrisoula Kakoulidou, Catherine P. Raptopoulou, Vassilis Psycharis, Dimitris P. Kessissoglou, Ioanna Zoi, Athanasios N. Papadopoulos, George Psomas
      From the reaction of ZnCl2 with the non-steroidal anti-inflammatory drug diflunisal (Hdifl), complex [Zn(difl-O)2(MeOH)4], 1 was formed, while in the presence of a N,N′-donor heterocyclic ligand 2,2′-bipyridylamine (bipyam), 2,2′-bipyridine (bipy), 1,10-phenanthroline (phen) and 2,2′-dipyridylketone oxime (Hpko), the complexes [Zn(difl-O,O')2(bipyam)], 2, [Zn(difl-O,O′)2(bipy)], 3, [Zn(difl-O,O′)2(phen)], 4 and [Zn(difl-O)2(Hpko)2], 5 were isolated, respectively. The complexes were characterized by physicochemical and spectroscopic techniques and the crystal structures of complexes 2, 3 and 5 were determined by X-ray crystallography. The ability of the complexes to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals and to inhibit soybean lipoxygenase was studied and the complexes were more active than free Hdifl. The interaction of the complexes with serum albumins was monitored by fluorescence emission spectroscopy and the corresponding binding constants were calculated. UV–vis spectroscopy, viscosity measurements and fluorescence emission spectroscopy for the competitive studies of the complexes with ethidium bromide were employed to investigate the interaction of the complexes with calf-thymus DNA and revealed intercalation as the most possible DNA-binding mode. Computational techniques were used to identify possible binding sites both albumins and DNA, and determine the druggability of human and bovine serum albumins with the five novel complexes. The majority of the complexes are stronger binders than the free Hdifl. This is the first study incorporating experimental and computational results to explore the binding activity of metal-NSAID complexes with DNA and serum albumins, suggesting their application as potential metallodrugs.
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      PubDate: 2017-02-15T11:26:58Z
      DOI: 10.1016/j.jinorgbio.2017.02.010
       
  • Comparative study of hydrolytic and electron-driven processes in
           carboplatin biotransformation
    • Authors: Janina Kuduk-Jaworska; Jerzy J. Jański; Szczepan Roszak
      Abstract: Publication date: Available online 11 February 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Janina Kuduk-Jaworska, Jerzy J. Jański, Szczepan Roszak
      The results of computational simulation of reaction courses mimicking the transformation of carboplatin from pro-drug into its active shape, responsible for cytotoxic effect, are reported. Implementing the density functional theory (DFT) calculations and the supermolecular approach, we explored the pathways representing two disparate models of carboplatin bioactivation: (1) based on paradigm of carboplatin aquation, and (2) based on new hypothesis that transformation is controlled by electron-transfer processes. The calculated geometrical and thermodynamic parameters were used for evaluation of pathways. In contrast to carboplatin hydrolysis, representing a typical two stage SN2 mechanism, the postulated electron-driven reactions proceed under the dissociative electron attachment (DEA) mechanism. The reaction profiles predict endothermic effect in both stages of hydrolytic course and final exothermic effects for electron-driven processes. The most effective are hybrid processes including two-stages: water and subsequent electron impact on transformed carboplatin. The aqua-products, manifesting strong electron-affinity, can be the active form of drug capable to cytotoxic interaction with DNA, not only as alkylating agent but also as electron-acceptor. Concluding, the hybrid transformation of carboplatin is more favourable than hydrolytic.
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      PubDate: 2017-02-15T11:26:58Z
      DOI: 10.1016/j.jinorgbio.2017.02.003
       
  • Synthetic investigation, physicochemical characterization and
           antibacterial evaluation of ternary Bi(III) systems with hydroxycarboxylic
           acid and aromatic chelator substrates
    • Authors: C.M. Nday; E. Halevas; A. Tsiaprazi-Stamou; D. Eleftheriadou; A. Hatzidimitriou; G. Jackson; D. Reid; A. Salifoglou
      Abstract: Publication date: Available online 11 February 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): C.M. Nday, E. Halevas, A. Tsiaprazi-Stamou, D. Eleftheriadou, A. Hatzidimitriou, G. Jackson, D. Reid, A. Salifoglou
      Due to its physical and chemical properties, bismuth (Bi(III)) is widely used in the treatment of several gastrointestinal and skin diseases, and infections caused by bacteria. Herein, its known antimicrobial potential was taken into consideration in the synthesis of two new hybrid ternary materials of Bi(III) with the physiological α-hydroxycarboxylic glycolic acid and 1,10-phenanthroline (phen), [Bi2(C2H2O3)2(C2H3O3)(NO3)]n .nH2O (1) and [Bi(C12H8N2)(NO3)4](C10H8N4) (2), aiming at improving its antibacterial properties. Their physicochemical characterization was carried out through elemental analysis, FT-IR, atomic absorption spectroscopy, single crystal X-ray diffraction, thermogravimetric analysis (TGA), photoluminescence, and 13C MAS-NMR techniques. The antimicrobial activity of the title complexes was directly linked to Bi(III) coordination environment and the incipient aqueous chemistry. For their antibacterial assessment, minimum inhibitory concentration (MIC), zone of inhibition (ZOI), and bacteriostatic-bacteriocidal activity were determined in various Gram positive (Staphylococcus aureus, Bacillus subtilis and Bacillus cereus) and Gram negative (Escherichia coli and Xanthomonas campestris) bacterial cultures, in reference to a positive control (ampicillin), encompassing further comparisons with literature data. The findings reveal that the new hybrid bismuth materials have significant antimicrobial effects against the employed bacteria. Specifically, 2 exhibits better antimicrobial properties than free Bi(NO3)3 and phen. On the other hand, 1 is bacteriostatic toward four microorganisms except X. campestris, with 2 being bacteriocidal toward four microorganisms except B. cereus. Collectively, the new hybrid, well-defined, and two of the rarely crystallographically characterized Bi(III) materials a) exhibit properties reflecting their composition and structure, and b) are expected to contribute to the development of efficient metallodrugs against drug-resistant bacterial infections.
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      PubDate: 2017-02-15T11:26:58Z
      DOI: 10.1016/j.jinorgbio.2017.02.007
       
  • Aspartate aminotransferase is potently inhibited by copper complexes:
           Exploring copper complex-binding proteome
    • Authors: Yuqi Jia; Liping Lu; Caixia Yuan; Sisi Feng; Miaoli Zhu
      Abstract: Publication date: Available online 11 February 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Yuqi Jia, Liping Lu, Caixia Yuan, Sisi Feng, Miaoli Zhu
      Recent researches indicated that a copper complex-binding proteome that potently interacted with copper complexes and then influenced cellular metabolism may exist in organism. In order to explore the copper complex-binding proteome, a copper chelating ion-immobilized affinity chromatography (Cu-IMAC) column and mass spectrometry were used to separate and identify putative Cu-binding proteins in primary rat hepatocytes. A total of 97 putative Cu-binding proteins were isolated and identified. Five higher abundance proteins, aspartate aminotransferase (AST), malate dehydrogenase (MDH), catalase (CAT), calreticulin (CRT) and albumin (Alb) were further purified using a SP, and (or) Q-Sepharose Fast Flow column. The interaction between the purified proteins and selected 11 copper complexes and CuCl2 was investigated. The enzymes inhibition tests demonstrated that AST was potently inhibited by copper complexes while MDH and CAT were weakly inhibited. Schiff-based copper complexes 6 and 7 potently inhibited AST with the IC50 value of 3.6 and 7.2μM, respectively and exhibited better selectivity over MDH and CAT. Fluorescence titration results showed the two complexes tightly bound to AST with binding constant of 3.89×106 and 3.73×106 M−1, respectively and a stoichiometry ratio of 1:1. Copper complex 6 was able to enter into HepG2 cells and further inhibited intracellular AST activity.
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      PubDate: 2017-02-15T11:26:58Z
      DOI: 10.1016/j.jinorgbio.2017.02.011
       
  • Interplay between autophagy and apoptosis in selenium deficient
           cardiomyocytes in chicken
    • Authors: Jie Yang; Yuan Zhang; Sattar Hamid; Jingzeng Cai; Qi Liu; Hao Li; Rihong Zhao; Hong Wang; Shiwen Xu; Ziwei Zhang
      Abstract: Publication date: Available online 10 February 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Jie Yang, Yuan Zhang, Sattar Hamid, Jingzeng Cai, Qi Liu, Hao Li, Rihong Zhao, Hong Wang, Shiwen Xu, Ziwei Zhang
      Dietary selenium (Se) deficiency can cause heart dysfunction, however the exact mechanism remains unclear. To understand this mechanism, 180day-old chicks, divided into two groups, C (control group) and L (low Se group), were fed with either a Se-sufficient (0.23mg/kg) or Se-deficient (0.033mg/kg) diets for 25days, respectively. Heart tissues and blood samples were collected. In L group, the activities of serum creatine kinase (CK) and creatine kinase-myoglobin (CK-MB) increased and typical ultrastructural apoptotic features were observed. Se deficiency up-regulated the mRNA levels of Cysteinyl aspartate specific proteinase 3 (Caspase-3), Cysteinyl aspartate specific proteinase 8 (Caspase-8), Cysteinyl aspartate specific proteinase 9 (Caspase-9), B cell lymphoma/leukemia 2 (Bcl-2), Bcl-2 Associated X Protein (Bax), (P <0.05), whereas, the mRNA levels of Microtubuleassociated protein light chains 3-1 (LC3-1), Autophagy associated gene 5 (ATG-5), Mammalian target of rapamycin (mTOR), Dynein and Becline-1 were down-regulated (P <0.05). Noticeably, Microtubuleassociated protein light chains 3-2 (LC3-2) mRNA level increased (P <0.05) by 20%. Western blot results showed that Se deficiency decreased the expression of Becline-1 and LC3-1 protein, however, the expression of Bax, Caspase-3 and Cysteinyl aspartate specific proteinase 12 (Caspase-12) increased at protein levels. The present study revealed that Se deficiency induced apoptosis while inhibited autophagy in chicken cardiomyocytes through Bax/Bcl-2 inhibition and caspases-mediated cleavage of Becline-1. Moreover, correlation analysis illustrates that apoptosis and autophagy might function contradictorily. Altogether we conclude that Se deficient chicken cardiomyocytes experienced apoptosis rather than autophagy which is considered to be more pro-survival.
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      PubDate: 2017-02-15T11:26:58Z
      DOI: 10.1016/j.jinorgbio.2017.02.006
       
  • Probing nitrite coordination in horseradish peroxidase by resonance Raman
           spectroscopy: Detection of two binding sites
    • Authors: Androulla Ioannou; Eftychia Pinakoulaki
      Abstract: Publication date: Available online 25 January 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Androulla Ioannou, Eftychia Pinakoulaki
      Nitrite is a powerful oxidant that affects the activity of peroxidases towards various substrates and leads to heme macrocycle modifications in members of the peroxidase family, such as the horseradish peroxidase (HRP). We have applied resonance Raman spectroscopy to investigate the structural properties of the species formed in the reaction of NO2 − with the ferric form of HRP. Our data demonstrate that the heme nitrovinyl group is partially formed at near neutral pH, without coordination of NO2 − to the heme Fe. Nitrite coordinates to the heme Fe at acidic pH in the nitro binding mode, characterized by the detection of the ν(Fe-NO2) at 563cm−1, δ(FeNO2) at 822cm−1 and νsym(NO2) at 1272cm−1. The sensitivity of the vibrations of the heme Fe-nitro complex to H/D exchange indicates H-bonding interaction of the heme-bound ligand with the distal environment that determines the NO2 − binding mode. A model describing the different modes of NO2 − binding in HRP is presented.
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      PubDate: 2017-01-28T01:05:19Z
      DOI: 10.1016/j.jinorgbio.2017.01.010
       
  • The Met80Ala and Tyr67His/Met80Ala mutants of human cytochrome c shed
           light on the reciprocal role of Met80 and Tyr67 in regulating ligand
           access into the heme pocket
    • Authors: Chiara Ciaccio; Lorenzo Tognaccini; Theo Battista; Manuela Cervelli; Barry D. Howes; Roberto Santucci; Massimo Coletta; Paolo Mariottini; Giulietta Smulevich; Laura Fiorucci
      Abstract: Publication date: Available online 24 January 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Chiara Ciaccio, Lorenzo Tognaccini, Theo Battista, Manuela Cervelli, Barry D. Howes, Roberto Santucci, Massimo Coletta, Paolo Mariottini, Giulietta Smulevich, Laura Fiorucci
      The spectroscopic and functional properties of the single Met80Ala and double Tyr67His/Met80Ala mutants of human cyt c have been investigated in their ferric and ferrous forms, and in the presence of different ligands, in order to clarify the reciprocal effect of these two residues in regulating the access of exogenous molecules into the heme pocket. In the ferric state, both mutants display an aquo high spin and a low spin species. The latter corresponds to an OH– ligand in Met80Ala but to a His in the double mutant. The existence of these two species is also reflected in the functional behavior of the mutants. The observation that (i) a significant peroxidase activity is present in the Met80Ala mutants, (ii) the substitution of the Tyr67 by His leads to only a slight increase of the peroxidase activity in the Tyr67His/Met80Ala double mutant with respect to WT, while the Tyr67His mutant behaves as WT, as previously reported, suggests that the peroxidase activity of cyt c is linked to an overall conformational change of the heme pocket and not only to the disappearance of the Fe-Met80 bond. Therefore, in human cyt c there is an interplay between the two residues at positions 67 and 80 that affects the conformation of the distal side of the heme pocket, and thus the sixth coordination of the heme.
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      PubDate: 2017-01-28T01:05:19Z
      DOI: 10.1016/j.jinorgbio.2017.01.008
       
  • Comparison of extracellular Cys/Trp motif between Schizosaccharomyces
           pombe Ctr4 and Ctr5
    • Authors: Mariko Okada; Takashi Miura; Takakazu Nakabayashi
      Abstract: Publication date: Available online 22 January 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Mariko Okada, Takashi Miura, Takakazu Nakabayashi
      The reduction and binding of copper ions to the Cys/Trp motif, which is characterized by two cysteines and two tryptophans, in the extracellular N-terminal domain of the copper transporter (Ctr) protein of fungi are investigated using the model peptides of Ctr4 and Ctr5 from Schizosaccharomyces pombe. The Cys/Trp motif of Ctr5 can reduce Cu(II) and ligate Cu(I), which is the same as that of Ctr4 previously reported. Titration of Cu(II) and Cu(I) ions indicates that both the Cys/Trp motifs of Ctr4 and Ctr5 reduce two Cu(II) and bind two Cu(I) per one peptide. However, the coordination structure of the Cu(I)-peptide complex differs between Ctr4 and Ctr5. Cu(I) is bound to the Cys/Trp motif of Ctr5 via cysteine thiolate-Cu(I) bonds and cation-π interaction with tryptophan, as reported for Ctr4, and a histidine residue in the Cys/Trp motif of Ctr5 is suggested to interact with Cu(I) via its Nτ atom. Ctr4 and Ctr5 exhibit a heterotrimeric form within cell membranes and the copper transport mechanism of the Ctr4/Ctr5 heterotrimer is discussed along with quantitative evaluation of the Cu(I)-binding constant of the Cys/Trp motif.
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      PubDate: 2017-01-28T01:05:19Z
      DOI: 10.1016/j.jinorgbio.2017.01.009
       
  • Crystal structure, cytotoxicity and action mechanism of Zn(II)/Mn(II)
           complexes with isoquinoline ligands
    • Authors: Feng-Yang Wang; Qian-Yu Xi; Ke-Bin Huang; Xiao-Ming Tang; Zhen-Feng Chen; Yan-Cheng Liu; Hong Liang
      Abstract: Publication date: Available online 6 January 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Feng-Yang Wang, Qian-Yu Xi, Ke-Bin Huang, Xiao-Ming Tang, Zhen-Feng Chen, Yan-Cheng Liu, Hong Liang
      Four μ2-Cl bridged dinuclear metal complexes with isoquinoline ligands, (MPDQ)2Zn2Cl4 (1) (MPDQ=4.5-methylenedioxy-1-pyridinedihydroisoquinoline), (PYP)2Zn2Cl4 (2) (PYP=5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline), (MPDQ)2Mn2Cl4 (3),and (PYP)2Mn2Cl4 (4) were synthesized and characterized. All complexes exhibited strong proliferation inhibition activity against various cancer cells. The underlying molecular mechanisms through which they caused the cancer cell death were also elucidated. Induction of apoptosis in MGC-803 cells by complex 2 was evidenced by annexin V+/PI− detection and DiD/DAPI staining assay. Further investigation revealed that complex 2 was able to induce intrinsic pathway-dependent apoptosis in cancer cells by triggering DNA damage which was caused by the overproduction of reactive oxygen species. Based on these studies, we suggest that Zn(II) complexes containing isoquinoline ligands can be developed as candidates for anti-cancer chemotherapeutics.
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      PubDate: 2017-01-13T22:45:42Z
      DOI: 10.1016/j.jinorgbio.2017.01.001
       
  • New insights into the reaction capabilities of His195 adjacent to the
           active site of nitrogenase
    • Authors: Ian Dance
      Abstract: Publication date: Available online 5 January 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Ian Dance
      The active site of the enzyme nitrogenase is FeMo-co, a C-centred Fe7MoS9 cluster, connected to the surrounding MoFe protein via ligands Cys275 and His442. Density functional calculations, involving 14 additional surrounding amino acids, focus on His195 because its mutation causes important reactivity changes, including almost complete loss of ability to reduce N2 to NH3. The Nε side-chain of His195 is capable of hydrogen bonding to S2B, bridging Fe2 and Fe6 of FeMo-co, believed to be the main reaction domain of nitrogenase. Details are presented for the possible ways in which protonated or deprotonated Nε of His195 interact with S2B or S2B-H or Fe2 or Fe2-H or Fe-(H2). Movements of the His195 side-chain allow formation of a significant short dihydrogen bond between Nε of His195 and H on Fe2: Nε-H••H-Fe2, with H–H=1.39Å. It is shown that a 180° rotation of the imidazole ring of His195 is not able to facilitate transfer of protons from the protein surface to FeMo-co. His195 is able to move H atoms to and from S2B, and the characteristics of H transfer between S2B and Nε of His195 are described, together with their dependence on the protonation state of His195 and the redox state of FeMo-co. The water molecule on the posterior Nδ side of His195 can mediate proton transfer to and from the side-chain of Tyr228. The accumulated results suggest that protonated His195 could be the agent for the first, most difficult, transfer of H to bound substrate N2.
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      PubDate: 2017-01-05T22:15:30Z
      DOI: 10.1016/j.jinorgbio.2017.01.005
       
  • Challenges encountered during development of Mn porphyrin-based, potent
           redox-active drug and superoxide dismutase mimic, MnTnBuOE-2-PyP5+, and
           its alkoxyalkyl analogues
    • Authors: Zrinka Rajic; Artak Tovmasyan; Otávio L. de Santana; Isabelle N. Peixoto; Ivan Spasojevic; Silmar A. do Monte; Elizete Ventura; Júlio S. Rebouças; Ines Batinic-Haberle
      Abstract: Publication date: Available online 5 January 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Zrinka Rajic, Artak Tovmasyan, Otávio L. de Santana, Isabelle N. Peixoto, Ivan Spasojevic, Silmar A. do Monte, Elizete Ventura, Júlio S. Rebouças, Ines Batinic-Haberle
      We disclose here the studies that preceded and guided the preparation of the metal-based, redox-active therapeutic Mn(III) meso-tetrakis(N-n-butoxyethylpyridyl)porphyrin, MnTnBuOE-2-PyP5+ (BMX-001), which is currently in Phase I/II Clinical Trials at Duke University as a radioprotector of normal tissue in cancer patients. N-substituted pyridylporphyrins are ligands for Mn(III) complexes that are among the most potent superoxide dismutase mimics thus far synthesized. To advance their design, thereby improving their physical and chemical properties and bioavailability/toxicity profiles, we undertook a systematic study on placing oxygen atoms into N-alkylpyridyl chains via alkoxyalkylation reaction. For the first time we show here the unforeseen structural rearrangement that happens during the alkoxyalkylation reaction by the corresponding tosylates. Comprehensive experimental and computational approaches were employed to solve the rearrangement mechanism involved in quaternization of pyridyl nitrogens, which, instead of a single product, led to a variety of mixed N-alkoxyalkylated and N-alkylated pyridylporphyrins. The rearrangement mechanism involves the formation of an intermediate alkyl oxonium cation in a chain-length-dependent manner, which subsequently drives differential kinetics and thermodynamics of competing N-alkoxyalkylation versus in situ N-alkylation. The use of numerous alkoxyalkyl tosylates, of different length of alkyl fragments adjacent to oxygen atom, allowed us to identify the set of alkyl fragments that would result in the synthesis of a single compound of high purity and excellent therapeutic potential.
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      PubDate: 2017-01-05T22:15:30Z
      DOI: 10.1016/j.jinorgbio.2017.01.003
       
  • Interaction of octahedral ruthenium(II) polypyridyl complex
           [Ru(bpy)2(PIP)]2+ with poly(U)•poly(A)*poly(U) triplex:increasing
           third-strand stabilization of the triplex without affecting the stability
           of the duplex
    • Authors: Zhiyuan Zhu; Mengna Peng; Jingwen Zhang; Lifeng Tan
      Abstract: Publication date: Available online 4 January 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Zhiyuan Zhu, Mengna Peng, Jingwen Zhang, Lifeng Tan
      Triple-helical RNA are of interest because of possible biological roles as well as the potential therapeutic uses of these structures, while the stability of triplexes is usually weaker than that of the Watson−Crick base pairing duplex strand due to the electrostatic repulsion between three polyanionic strands. Therefore, how to increase the stability of the specific sequences of triplexes are of importance. In this paper the binding of a Ru(II) complex, [Ru(bpy)2(PIP)]2+ (bpy = 2,2'-bipyridine, PIP = 2-phenyl-1H-imidazo[4,5-f]- [1,10]-phenanthroline), with poly(U).poly(A)*poly(U) triplex has been investigated by spectrophotometry, spectrofluorometry, viscosimetry and circular dichroism. The results suggest that [Ru(bpy)2(PIP)]2+ as a metallointercalator can stabilize poly(U)•poly(A)*poly(U) triplex (where • denotes the Watson-Crick base pairing and * denotes the Hoogsteen base pairing),while it stabilizes third-strand with no obvious effect on the duplex of poly(U)•poly(A), reflecting the binding of this complex with the triplex is favored by the Hoogsteen paired poly(U) third strand to a great extent.
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      PubDate: 2017-01-05T22:15:30Z
      DOI: 10.1016/j.jinorgbio.2017.01.004
       
  • Delineating hierarchy of selenotranscriptome expression and their response
           to selenium status in chicken central nervous system
    • Authors: Xiu-Qing Jiang; Chang-Yu Cao; Zhao-Yang Li; Wei Li; Cong Zhang; Jia Lin; Xue-Nan Li; Jing-Long Li
      Abstract: Publication date: Available online 4 January 2017
      Source:Journal of Inorganic Biochemistry
      Author(s): Xiu-Qing Jiang, Chang-Yu Cao, Zhao-Yang Li, Wei Li, Cong Zhang, Jia Lin, Xue-Nan Li, Jing-Long Li
      Selenium (Se) incorporated in selenoproteins as selenocysteine and supports various important cellular and organismal functions. We recently reported that chicken brain exhibited high priority for Se supply and retention under conditions of dietary Se deficiency and supernutrition Li et al. (2012) . However, the selenotranscriptome expressions and their response to Se status in chicken central nervous system (CNS) are unclear. To better understand the relationship of Se homeostasis and selenoproteins expression in chicken CNS, 1day-old HyLine White chickens were fed a low Se diet (Se-L, 0.028mg/g) supplemented with 4 levels of dietary Se (0 to 5.0mgSe/kg) as Na2SeO3 for 8weeks. Then chickens were dissected for getting the CNS, which included cerebral cortex, cerebellum, thalamus, bulbus cinereus and marrow. The expressions of selenoproteome which have 24 selenoproteins were detected by the quantitative real-time PCR array. The concept of a selenoprotein hierarchy was developed and the hierarchy of different regions in chicken CNS was existence, especially cerebral cortex and bulbus cinereus. The expression of selenoproteins has a hierarch while changing Se content, and Selenoprotein T (Selt), Selenoprotein K (Selk), Selenoprotein W (Selw), Selenoprotein U (Selu), Glutathione peroxidase 3 (Gpx3), Glutathione peroxidase 4 (Gpx4), Selenoprotein P (Sepp1), Selenoprotein O (Selo), Selenoprotein 15 (Sel15), Selenoprotein N (Seln), Glutathione peroxidase 2 (Gpx2) and Selenoprotein P 2 (Sepp2) take more necessary function in the chicken CNS. Therefore, we hypothesize that hierarchy of regulated the transcriptions of selenoproteome makes an important role of CNS Se metabolism and transport in birds.
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      PubDate: 2017-01-05T22:15:30Z
      DOI: 10.1016/j.jinorgbio.2017.01.002
       
  • New silver complexes with bioactive glycine and nicotinamide molecules –
           Characterization, DNA binding, antimicrobial and anticancer evaluation
    • Authors: Michaela Rendošová; Zuzana Vargová; Juraj Kuchár; Danica Sabolová; Štefan Levoča; Júlia Kudláčová; Helena Paulíková; Daniela Hudecová; Veronika Helebrandtová; Miroslav Almáši; Mária Vilková; Michal Dušek; Dáša Bobáľová
      Pages: 1 - 12
      Abstract: Publication date: March 2017
      Source:Journal of Inorganic Biochemistry, Volume 168
      Author(s): Michaela Rendošová, Zuzana Vargová, Juraj Kuchár, Danica Sabolová, Štefan Levoča, Júlia Kudláčová, Helena Paulíková, Daniela Hudecová, Veronika Helebrandtová, Miroslav Almáši, Mária Vilková, Michal Dušek, Dáša Bobáľová
      This study introduces a pair of newly synthesized silver complexes, [Ag2(HGly)2]n(NO3)2n (1) and [Ag(Nam)2]NO3·H2O (2) (Gly – glycine, Nam – nicotinamide), that were prepared and characterized by relevant methods in solid state (elemental, spectral, thermal and structural analysis) and their stability in solution was verified by 1H NMR measurements. Moreover, suitable reaction conditions were observed by potentiometry depending on pH in case of binary system Ag-Gly. X-ray analysis confirmed argentophilic interactions in complex 1 with an Ag1-Ag2 distance of 2.8018(6) Å. Antimicrobial testing indicates higher growth inhibition effect of complex 1 than complex 2. Moreover the effectivity of both complexes against bacteria (Staphylococcus aureus and Escherichia coli) is superior (or similar) to that of the commercially available Ag(I) sulfadiazine, AgSD (used, for example, in Dermazine cream). The binding of the Ag(I) complexes to calf thymus DNA was investigated using electronic absorption, fluorescence and circular dichroism spectrophotometry. The Stern–Volmer quenching constants obtained from the linear quenching plot were estimated in the range from 2.01×103 to 20.34×103 M−1. The results of topoisomerase I and topoisomerase II (Topo I and Topo II) inhibition assay suggested that complex 2 inhibits the enzyme activity of both enzymes at a concentration of 2μM. The cytotoxicity of both complexes on L1210 leukemia cells was revealed to be approximately three times higher than that of cisplatin. Moreover, the new Ag(I) complexes also induced apoptosis of the leukemia cells. The high DNA binding activity of these complexes is considered to be responsible for their cytotoxic effects.
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      PubDate: 2016-12-21T11:50:33Z
      DOI: 10.1016/j.jinorgbio.2016.12.003
      Issue No: Vol. 168 (2016)
       
  • Studies on the mechanism of action of antitumor bis(aminophenolate)
           ruthenium(III) complexes
    • Authors: Orsolya Dömötör; Rodrigo F.M. de Almeida; Leonor Côrte-Real; Cristina P. Matos; Fernanda Marques; António Matos; Carla Real; Tamás Kiss; Éva Anna Enyedy; M. Helena Garcia; Ana Isabel Tomaz
      Pages: 27 - 37
      Abstract: Publication date: March 2017
      Source:Journal of Inorganic Biochemistry, Volume 168
      Author(s): Orsolya Dömötör, Rodrigo F.M. de Almeida, Leonor Côrte-Real, Cristina P. Matos, Fernanda Marques, António Matos, Carla Real, Tamás Kiss, Éva Anna Enyedy, M. Helena Garcia, Ana Isabel Tomaz
      Two recently published Ru(III) complexes bearing (N2O2) tetradentate bis(aminophenolate) ligands, formulated as [Ru(III)(salan)(PPh3)Cl] (salan is the tetradentate ligand 6,6′-(1S,2S)-cyclohexane-1,2-diylbis(azanediyl)bis(methylene)bis(3-methoxyphenol) in complex 1, or 2,2′-(1S,2S)-cyclohexane-1,2-diylbis(azanediyl)bis(methylene)bis(4-methoxyphenol) in complex 2; PPh3 is triphenylphosphane) and found very active against ovarian and breast adenocarcinoma human cells were studied to outline their antitumor mode of action. The human cisplatin-sensitive ovarian adenocarcinoma line A2780 was used herein as the cell model. At a 24h challenge (similarly as found before for 72h) both complexes are active, their cytotoxicity being comparable to that of cisplatin in the same conditions. As a possible target in the cell for their action, the interaction of 1 and 2 with DNA was assessed through displacement of well-established DNA fluorescent probes (ethidium bromide, EB, and 4′,6-diamidino-2-phenylindole, DAPI) through steady-state and time-resolved fluorescence spectroscopy. The whole emission spectra were analyzed globally for the binary DNA–probe and ternary DNA–probe–Ru(III) complex systems. Both Ru(III) complexes can displace EB and bind to DNA with similar and moderate strong affinity with conditional stability constants of logK’=(5.05±0.01) for 1 and logK’=(4.79±0.01) for 2. The analysis of time-domain fluorescence intensity decays confirmed both qualitatively and quantitatively the model used to describe the binding and competition processes. Cell studies indicated that apoptosis is the major mechanism of cell death for both complexes, with 2 (the more active complex) promoting that process more efficiently than 1. Transmission electron micrographs revealed clear alterations on intracellular organization consistent with the induction of programmed cell death processes.
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      PubDate: 2016-12-21T11:50:33Z
      DOI: 10.1016/j.jinorgbio.2016.12.008
      Issue No: Vol. 168 (2016)
       
  • Synthesis, characterization, DNA interactions and antiproliferative
           activity on glioblastoma of iminopyridine platinum(II) chelate complexes
    • Authors: Inmaculada Posadas; Carlos Alonso-Moreno; Iván Bravo; Fernando Carrillo-Hermosilla; Andrés Garzón; Noemí Villaseca; Isabel López-Solera; José Albaladejo; Valentín Ceña
      Abstract: Publication date: Available online 19 December 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Inmaculada Posadas, Carlos Alonso-Moreno, Iván Bravo, Fernando Carrillo-Hermosilla, Andrés Garzón, Noemí Villaseca, Isabel López-Solera, José Albaladejo, Valentín Ceña
      A series of iminopyridine platinum chelate compounds has been prepared and characterized by NMR spectroscopy and single-crystal X-ray diffraction. The complexes were evaluated in C6 tumoral cells as an in vitro model for glioblastoma multiforme. The DNA-binding properties of these complexes were studied by UV–Vis absorption and fluorescence spectroscopy and Density Functional Theory calculations were performed in an effort to rationalize the observed properties at the molecular level. The most promising drug candidate displayed a similar potency in inducing cell death to the clinically used reference compound and showed significant inhibition of glioblastoma cell proliferation. Moreover, this compound had a safer profile than cisplatin on non-tumoral cells.
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      PubDate: 2016-12-21T11:50:33Z
      DOI: 10.1016/j.jinorgbio.2016.11.032
       
  • Synthesis, photophysical properties and structures of organotin- Schiff
           bases utilizing aromatic amino acid from the chiral pool and evaluation of
           the biological perspective of a triphenyltin compound
    • Authors: Tushar S. Basu Baul; Pelesakuo Kehie; Andrew Duthie; Nikhil Guchhait; Nune Raviprakash; Raveendra B. Mokhamatam; Sunil K. Manna; Nerina Armata; Michelangelo Scopelliti; Ruimin Wang; Ulli Englert
      Abstract: Publication date: Available online 16 December 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Tushar S. Basu Baul, Pelesakuo Kehie, Andrew Duthie, Nikhil Guchhait, Nune Raviprakash, Raveendra B. Mokhamatam, Sunil K. Manna, Nerina Armata, Michelangelo Scopelliti, Ruimin Wang, Ulli Englert
      Five new organotin(IV) complexes of compositions [Me2SnL1] (1), [Me2SnL2]n (2), [Me2SnL3] (3), [Ph3SnL1H]n (4) and [Ph3SnL3H] (5) (where L1 =(2S)-2-((E)-((Z)-4-hydroxypent-3-en-2-ylidene)amino)-3-(1H-indol-3-yl)propanoate, L2 =(2S)-(E)-2-((2-hydroxybenzylidene)amino)-3-(1H-indol-3-yl)propanoate and L3 =(2S)-(E)-2-((1-(2-hydroxyphenyl)ethylidene)amino)-3-(1H-indol-3-yl)propanoate were synthesized and spectroscopically characterized. The crystal structures of 1–4 were determined. For the dimethyltin derivative 2, a polymeric chain structure was observed as a result of a long Sn┄O contact involving the exocyclic carbonyl oxygen-atom from the tridentate ligand of a neighboring Sn-complex unit. The tin atom in this complex has a distorted octahedral coordination geometry, in which the long SnO bond is almost trans to the tridentate ligand nitrogen-atom. In contrast, the dimethyltin(IV) complexes 1 and 3 displayed discrete monomeric structures where the tin atom has distorted trigonal-bipyramidal geometry with the two coordinating L oxygen atoms defining the axial positions. On the other hand, 4 is a chain polymer in the solid state. The ligand-bridged Sn-atoms adopt a trans-Ph3SnO2 trigonal-bipyramidal configuration with equatorial phenyl groups. A carboxylato oxygen atom from one and the hydroxyl oxygen of the successive ligand in the chain occupy the axial positions. The solution structures were predicted by the use of 119Sn NMR chemical shifts. The photophysical properties of the complexes were investigated in the solid and in solution. The triphenyltin(IV) compound 4 was tested in detail ex vivo against A375 (human melanoma) cell line, exhibiting an IC50 value of 261nM to induce cell death as assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay without significant alteration of cytolysis as determined by lactate dehydrogenase (LDH) assay. Compound 4-mediated potent cell death was also determined by Live and Dead assay and caspase-mediated cleavage of poly-ADP ribose (PARP). Potent cell death activity was not observed in primary cells, like blood-derived peripheral mononuclear cells (PBMC). Compound 4 inhibited the diphenyl hexatriene (DPH) binding to cells and decreased the micro viscosity in a dose-dependent manner. Additionally, the interaction ability between 4 and cyclodextrin (CD) was determined by modelling approach.
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      PubDate: 2016-12-21T11:50:33Z
      DOI: 10.1016/j.jinorgbio.2016.12.001
       
  • Antileukemic activity of an arsenomolybdate in the human HL-60 and U937
           leukemia cells
    • Authors: Chunyan Li; Hongqian Cao; Jiaheng Sun; Rui Tian; Dongbei Li; Yanfei Qi; Wei Yang; Juan Li
      Abstract: Publication date: Available online 16 December 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Chunyan Li, Hongqian Cao, Jiaheng Sun, Rui Tian, Dongbei Li, Yanfei Qi, Wei Yang, Juan Li
      The antileukemic activity, mechanisms and serum albumin interactions of an arsenomolybdate, K2Na[AsMo6O21(O2CCH2NH3)3]·6H2O (1), was evaluated in the human leukemia HL-60 and U937 cells. The results indicated that 1 could inhibit the proliferation of both leukemia cell lines in a dose-dependent manner with the 50% lethal concentration (IC50) value of 8.61μM for HL-60 and 14.50μM for U937 at 24h, compare to the positive controls, all-trans retinoic acid (ATRA) with IC50 value of 20.76μM and 14.85μM,and As2O3 with IC50 value of 6.40μM and 8.75μM at 24h, respectively (P <0.05). Furthermore, the anti-leukemia activity of compound 1 might be medicated by arresting the leukemic cells in the G1 phase and inducing apoptosis via caspase-3 and bcl-2 regulatory proteins. Spectroscopic techniques results showed that the fluorescence of human serum albumin was quenched by compound 1, and the quenching mechanism was mainly static quenching. Compound 1 might be a potential medicinal candidate against acute promyelocytic leukemia.
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      PubDate: 2016-12-21T11:50:33Z
      DOI: 10.1016/j.jinorgbio.2016.12.002
       
  • An unlikely DNA cleaving agent: A photo-active trinuclear Cu(II) complex
           based on hexaazatriphenylene
    • Authors: Dominique E. Williams; Christina M. Fischer; Miki Kassai; Lourdes Gude; María-José Fernández; Antonio Lorente; Kathryn B. Grant
      Abstract: Publication date: Available online 15 December 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Dominique E. Williams, Christina M. Fischer, Miki Kassai, Lourdes Gude, María-José Fernández, Antonio Lorente, Kathryn B. Grant
      This paper describes the synthesis of a trinuclear Cu(II) complex (4) containing a central 1,4,5,8,9,12-hexaazatriphenylene-hexacarboxylate (hat) core (3). Low, micromolar concentrations of the negatively charged parent ligand 3 and the neutral trinuclear complex 4 were found to photocleave negatively charged pUC19 plasmid DNA with high efficiency at neutral pH (350nm, 50min, 22°C). The interactions of complex 4 with double-helical DNA were studied in detail. Scavenger and colorimetric assays pointed to the formation of Cu(I), superoxide anion radicals, hydrogen peroxide, and hydroxyl radicals during photocleavage reactions. UV–visible absorption, circular dichroism, DNA thermal denaturation, and fluorescence data suggested that the Cu(II) complex contacts double-stranded DNA in an external fashion. The persistent association of ligand 3 and complex 4 with Na(I) and/or other cations in aqueous solution might facilitate electrostatic DNA interactions.
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      PubDate: 2016-12-21T11:50:33Z
      DOI: 10.1016/j.jinorgbio.2016.12.007
       
  • Potent Anticancer Activity of A New Bismuth (III) Complex against Human
           Lung Cancer Cells
    • Authors: Ruizhuo Ouyang; Yang Yang; Xiao Tong; Kai Feng; Yaoqin Yang; Huihong Tao; Xiaoshen Zhang; Tianyu Zong; Penghui Cao; Fei Xiong; Ning Guo; Yuhao Li; Yuqing Miao; Shuang Zhou
      Abstract: Publication date: Available online 11 December 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Ruizhuo Ouyang, Yang Yang, Xiao Tong, Kai Feng, Yaoqin Yang, Huihong Tao, Xiaoshen Zhang, Tianyu Zong, Penghui Cao, Fei Xiong, Ning Guo, Yuhao Li, Yuqing Miao, Shuang Zhou
      The aim of this work is experimental study of an interesting bismuth(III) complex derived from pentadentate 2.6-pyridinedicarboxaldehyde bis(4 N–methylthiosemicarbazone), [BiL(NO3)2]NO3 {L=2.6-pyridinedicarboxaldehyde bis(4N–methylthiosemicarbazone)}. A series of in vitro biological studies indicate that the newly prepared [BiL(NO3)2]NO3 greatly suppressed colony formation, migration and significantly induced apoptosis of human lung cancer cells A549 and H460, but did not obviously decrease the cell viability of non-cancerous human lung fibroblast (HLF) cell line, showing much higher anticancer activities than its parent ligands, especially with half maximum inhibitory concentration (IC50) <3.5μM. Moreover, in vivo study provides enough evidence that the treatment with [BiL(NO3)2]NO3 effectively inhibited A549 xenograft tumor growth on tumor-bearing mice (10mg/kg, tumor volume reduced by 97.92% and tumor weight lightened by 94.44% compared to control) and did not indicate harmful effect on mouse weight and liver. These results suggest that the coordination of free ligand with Bi(III) might be an interesting and potent strategy in the discovery of new anticancer drug candidates.
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      PubDate: 2016-12-13T11:25:07Z
      DOI: 10.1016/j.jinorgbio.2016.12.006
       
  • Synergistic antibacterial effect of Bi2S3 nanospheres combined with
           ineffective antibiotic gentamicin against methicillin-resistant
           Staphylococcus aureus
    • Authors: Lulu Ma; Jie Wu; Shilei Wang; Hao Yang; Donghui Liang; Zhong Lu
      Abstract: Publication date: Available online 10 December 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Lulu Ma, Jie Wu, Shilei Wang, Hao Yang, Donghui Liang, Zhong Lu
      In this paper, Bi2S3 nanospheres with size of 212nm were prepared by a simple hydrothermal process. The selectively enhanced antibacterial effects of Bi2S3 nanospheres with three classes of ineffective antibiotics, β-lactam (cefuroxime, CXM; cefotaxime, CTX and piperacillin, PIP), quinolone (ciprofloxacin, CIP) and aminoglycoside (gentamicin, GEN) against clinical isolated methicillin-resistant Staphylococcus aureus (MRSA) were investigated for the first time. GEN shows significantly synergistic growth inhibition against MRSA when combined with Bi2S3 nanospheres, while CXM, CTX, PIP and CIP do not. Raman spectroscopy and Z potential studies reveal that Bi2S3 could interact with GEN and the combination showed small electronegativity, which probably induced the increase of GEN content in cytoplasm of bacteria. Furthermore, the combination of Bi2S3 nanospheres and GEN can destroy the bacterial membrane function and induce more bactericidal reactive oxygen generation than that of Bi2S3 or GEN alone. The cytotoxicity test indicates that the combination of Bi2S3 and GEN presented low toxicity to human normal hepatocyte L02. This work shows that Bi2S3 nanospheres can be used to enhance the action of ineffective antibiotic GEN against MRSA, thus strengthening the antibiotic capacity for fighting MRSA infections.
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      PubDate: 2016-12-13T11:25:07Z
      DOI: 10.1016/j.jinorgbio.2016.12.005
       
  • Silver complexes of ligands derived from adamantylamines : Water-soluble
           silver-donating compounds with antibacterial properties
    • Authors: Jorge Jimenez; Indranil Chakraborty; Mauricio Rojas-Andrade; Pradip K. Mascharak
      Abstract: Publication date: Available online 10 December 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Jorge Jimenez, Indranil Chakraborty, Mauricio Rojas-Andrade, Pradip K. Mascharak
      Two new silver(I) complexes, namely [Ag(qyAm)2](CF3SO3) (1) and [Ag(qyTAm)2](CF3SO3) (2), (qyAm =2-(quinonyl)iminoadamantane, qyTAm =2-(quinonyl)iminotriazaadamantane) have been synthesized and characterized by elemental analyses, 1H NMR, IR, electronic absorption spectroscopy, and X-ray diffraction. The coordination geometry of the silver center in both complexes is distorted tetrahedral where their respective qyAm and qyTAm ligand bind in a bidentate fashion using the imine and quinoline nitrogen atoms. Complex 2 is soluble in water and exhibits strong antimicrobial actions on both Gram-negative (E. coli, and P. aeruginosa) and Gram-positive (S. aureus) bacteria. The MIC values for complex 2 (4, 4, and 8μg for E. coli, P. aeruginosa, and S. aureus, respectively) are comparable to MIC values of silver nitrate and silver sulfadiazine.
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      PubDate: 2016-12-13T11:25:07Z
      DOI: 10.1016/j.jinorgbio.2016.12.009
       
  • Biophysical characterization and antineoplastic activity of new
           bis(thiosemicarbazonato) Cu(II) complexes
    • Authors: Elisa Palma; Filipa Mendes; Goreti Ribeiro Morais; Inês Rodrigues; Isabel Cordeiro Santos; Maria Paula C. Campello; Paula Raposinho; Isabel Correia; Sofia Gama; Dulce Belo; Vítor Alves; Antero J. Abrunhosa; Isabel Santos; António Paulo
      Abstract: Publication date: Available online 23 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Elisa Palma, Filipa Mendes, Goreti Ribeiro Morais, Inês Rodrigues, Isabel Cordeiro Santos, Maria Paula C. Campello, Paula Raposinho, Isabel Correia, Sofia Gama, Dulce Belo, Vítor Alves, Antero J. Abrunhosa, Isabel Santos, António Paulo
      Aiming to explore alternative mechanisms of cellular uptake and cytotoxicity, we have studied a new family of copper(II) complexes (CuL 1 -CuL 4 ) with bis(thiosemicarbazone) (BTSC) ligands containing pendant protonable cyclic amines (morpholine and piperidine). Herein, we report on the synthesis and characterization of these new complexes, as well as on their biological performance (cytotoxic activity, cellular uptake, protein and DNA binding), in comparison with the parental Cu II ATSM (ATSM=diacetyl-bis(N4-methylthiosemicarbazonate) complex without pendant cyclic amines. The new compounds have been characterized by a range of analytical techniques including ESI-MS, IR spectroscopy, cyclic voltammetry, reverse-phase HPLC and X-ray spectroscopy. In vitro cytotoxicity studies revealed that the copper complexes are cytotoxic, unlike the corresponding ligands, with a similar potency to that of CuATSM. Unlike CuATSM, the new complexes were able to circumvent cisplatin cross-resistance. The presence of the protonable cyclic amines did not lead to an enhancement of the interaction of the complexes with human serum albumin or calf thymus DNA. However, CuL 1 –CuL 4 showed a remarkably augmented cellular uptake compared with CuATSM, as proved by uptake, internalization and externalization studies that were performed using the radioactive congeners 64 CuL 1 - 64 CuL 4 . The enhanced cellular uptake of CuL 1 -CuL 4 indicates that this new family of CuIIBTSC complexes deserves to be further evaluated in the design of metallodrugs for cancer theranostics.
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      PubDate: 2016-11-23T18:12:00Z
      DOI: 10.1016/j.jinorgbio.2016.11.026
       
  • Drug Discovery Targeting Heme-Based Sensors and Their Coupled Activities
    • Authors: Eduardo H.S. Sousa; Luiz Gonzaga de França Lopes; Gonzalo Gonzalez; Marie-Alda Gilles-Gonzalez
      Abstract: Publication date: Available online 20 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Eduardo H.S. Sousa, Luiz Gonzaga de França Lopes, Gonzalo Gonzalez, Marie-Alda Gilles-Gonzalez
      Heme-based sensors have emerged during the last 20years as being a large family of proteins that occur in all kingdoms of life. A myriad of biological adaptations are associated with these sensors, which include vasodilation, and bacterial virulence, dormancy, chemotaxis, biofilm formation, among others. Due to the key activities regulated by these proteins along with many other systems that use similar output domains, there is a growing interest in developing small molecules as their regulators. Here, we review the development of potential activators and inhibitors for many of these systems, including human soluble guanylate cyclase, c-di-GMP-related enzymes, Mycobacterium tuberculosis DevR/DevS/DosT (differentially expressed in virulent strain response regulator/ sensor/ do rmancy s urvival sensor T ), the Rev.-erb-α and β nuclear receptor, among others. The possible roles of these molecules as biochemical tools, therapeutic agents, and novel antibiotics are critically examined.
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      PubDate: 2016-11-23T18:12:00Z
      DOI: 10.1016/j.jinorgbio.2016.11.022
       
  • Dimerization, redox properties and antioxidant activity of two
           manganese(III) complexes of difluoro- and dichloro-substituted Schiff-base
           ligands
    • Authors: Claudia Palopoli; Guillermo Gómez; Ana Foi; Fabio Doctorovich; Sonia Mallet-Ladeira; Christelle Hureau; Sandra Signorella
      Abstract: Publication date: Available online 18 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Claudia Palopoli, Guillermo Gómez, Ana Foi, Fabio Doctorovich, Sonia Mallet-Ladeira, Christelle Hureau, Sandra Signorella
      Two mononuclear MnIII complexes [Mn(3,5-F2salpn)(H2O)2][B(C6H5)4]·2H2O (1·2H2O) and [Mn(3,5-Cl2salpn)(OAc)(H2O)]·H2O (2·H2O), where H2salpn=1,3-bis(salicylidenamino)propane, have been prepared and characterized. The crystal structure of 1·H2O shows that this complex forms μ-aqua dimers with a short Mn⋯Mn distance of 4.93Å. Under anaerobic conditions, the two complexes are stable in solution and possess trans-diaxial symmetry with the tetradentate Schiff base ligand symmetrically arranged in the equatorial plane. When left in air, these complexes slowly dimerize to yield high-valent [MnIV 2(3,5-X2-salpn)2(μ-O)2] in which each X2-salpn ligand wraps the two Mn ions. This process is favored in basic medium where the deprotonation of the bound water molecule is concomitant with air oxidation. The two complexes catalyze the dismutation of superoxide (superoxide dismutase (SOD) activity) and peroxide (catalase (CAT) activity) in basic medium. The phenyl-ring substituents play an important role on the CAT reaction but have little effect on SOD activity. Kinetics and spectroscopic results indicate that 1 and 2 catalyze H2O2 disproportionation through a cycle involving MnIII 2 and MnIV 2 dimers, unlike related complexes with a more rigid and smaller chelate ring, which employ MnIII/MnV O monomers.
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      PubDate: 2016-11-23T18:12:00Z
      DOI: 10.1016/j.jinorgbio.2016.11.019
       
  • May glutamine addiction drive the delivery of antitumor cisplatin-based
           Pt(IV) prodrugs'
    • Authors: Mauro Ravera; Elisabetta Gabano; Stefano Tinello; Ilaria Zanellato; Domenico Osella
      Abstract: Publication date: Available online 17 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Mauro Ravera, Elisabetta Gabano, Stefano Tinello, Ilaria Zanellato, Domenico Osella
      A small series of Pt(IV) prodrugs containing Gln-like (Gln=glutamine) axial ligands has been designed with the aim to take advantage of the increased demand of Gln showed by some cancer cells (glutamine addiction). In complex 4 the Gln, linked through the α-carboxylic group is recognized by the Gln transporters, in particular by the solute carrier transporter SLC1A5. All compounds showed cellular accumulation, as well as antiproliferative activity, related to their lipophilicity, as already demonstrated for the majority of Pt(IV) prodrugs, that enter cells mainly by passive diffusion. On the contrary, when the Gln concentration in cell medium is near or lower to the physiological value, complex 4 acts as a Trojan horse: it enters SLC1A5-overexpressing cells, where, upon reduction, it releases the active metabolite cisplatin and the Gln-containing ligand, thus preventing any possible extrusion by the L-type amino acid transporter LAT1. This selective mechanism could decrease off-target accumulation of 4 and, consequently, Pt-associated side-effects.
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      PubDate: 2016-11-23T18:12:00Z
      DOI: 10.1016/j.jinorgbio.2016.11.024
       
  • Ferrocenyl naphthalene diimides as tetraplex DNA binders
    • Authors: Shinobu Sato; Shigeori Takenaka
      Abstract: Publication date: Available online 17 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Shinobu Sato, Shigeori Takenaka
      Seven ferrocenyl naphthalene diimide (FND) ligands were synthesized. Each had a higher affinity for tetraplex DNA than for either single- or double-stranded DNA. The FND binding affinities were >105 M−1 in 0.10M AcOH-AcONa or AcOH-AcOK (pH5.5) containing 0.10M NaCl or KCl. The FNDs with the highest binding affinities for tetraplex DNA showed 23- or 8-times higher preference for tetraplex DNA than for single- or double-stranded DNA, respectively. The current signals generated from the seven FNDs bound to the tetraplex DNA immobilized on the electrode were found to correlate with the binding affinities of these ligands for the tetraplex DNA. Furthermore, using the telomerase repeat amplification protocol assay, the FND ligands could be categorized into three groups: (a) inhibiting both telomerase and Taq polymerase, (b) inhibiting telomerase alone, and (c) inhibiting neither telomerase nor Taq polymerase.
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      PubDate: 2016-11-23T18:12:00Z
      DOI: 10.1016/j.jinorgbio.2016.11.020
       
  • Quercetin loading CdSe/ZnS nanoparticles as efficient antibacterial and
           anticancer materials
    • Authors: Xiaofang Yang; Weiwei Zhang; Zhiwei Zhao; Nuan Li; Zhipeng Mou; Dongdong Sun; Yongping Cai; Weiyun Wang; Yi Lin
      Abstract: Publication date: Available online 17 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Xiaofang Yang, Weiwei Zhang, Zhiwei Zhao, Nuan Li, Zhipeng Mou, Dongdong Sun, Yongping Cai, Weiyun Wang, Yi Lin
      Quercetin (Qe) plays an important role in inflammation, antibacterial, anticancer, and aging. However, Qe has extremely low water solubility, which is a major challenge in drug absorption. In this study, we described a simple method for synthesis of Qe/CdSe/ZnS nanoparticles (QCZ NPs). The QCZ NPs had an average diameter of 10nm and prominent yellow emission under UV irradiation. We investigated the antibacterial activity of QCZ NPs against drug-resistant Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) in vitro. Results showed that QCZ NPs had considerably more effective antibacterial activities than Qe or CdSe nanoparticles (CdSe NPs). Antibacterial experiment results showed that QCZ NPs acted against E. coli and B. subtilis by disrupting the bacterial cell wall and membrane. In vivo study, the QCZ NPs could cure inflammation and lesion which caused by E. coli. In anticancer assays, the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cell proliferation assays exhibited the cytotoxicity of QCZ NPs increased approximately 2–6 fold compared to raw Qe and CdSe NPs. Moreover, by using RT-CES (real-time cell electronic sensing) studies, we had demonstrated QCZ NPs have also an effect on migration and proliferation of BGC-823 cells. CdSe NPs loaded with Qe, these QCZ NPs exhibited excellent antibacterial (E. coli and B. subtilis) and anticancer (BGC-823) activities.
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      PubDate: 2016-11-17T18:00:02Z
      DOI: 10.1016/j.jinorgbio.2016.11.023
       
  • Low-dimensional compounds containing bioactive ligands. Part VIII: DNA
           interaction, antimicrobial and antitumor activities of ionic
           5,7-dihalo-8-quinolinolato palladium(II) complexes with K+ and Cs+ cations
           
    • Authors: Veronika Farkasová; Sayed Ali Drweesh; Andrea Lüköová; Danica Sabolová; Ivana D. Radojević; Ljiljana R. Čomić; Sava M. Vasić; Helena Paulíková; Stanislav Fečko; Tatiana Balašková; Mária Vilková; Ján Imrich; Ivan Potočňák
      Abstract: Publication date: Available online 16 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Veronika Farkasová, Sayed Ali Drweesh, Andrea Lüköová, Danica Sabolová, Ivana D. Radojević, Ljiljana R. Čomić, Sava M. Vasić, Helena Paulíková, Stanislav Fečko, Tatiana Balašková, Mária Vilková, Ján Imrich, Ivan Potočňák
      Starting from well-defined NH2(CH3)2[PdCl2(XQ)] complexes, coordination compounds of general formula Cat[PdCl2(XQ)] have been prepared by cationic exchange of NH2(CH3)2 + and Cat cations, where XQ are biologically active halogen derivatives of quinolin-8-ol (5-chloro-7-iodo-quinolin-8-ol (CQ), 5,7-dibromo-quinolin-8-ol (dBrQ) and 5,7-dichloro-quinolin-8-ol (dClQ)) and Cat is K+ or Cs+. The cation exchange of all prepared complexes, K[PdCl2(CQ)] (1), K[PdCl2(dClQ)] (2), K[PdCl2(dBrQ)] (3), Cs[PdCl2(CQ)] (4), Cs[PdCl2(dClQ)] (5) and Cs[PdCl2(dBrQ)] (6) was approved using IR spectroscopy, their structures in DMSO solution were elucidated by one- and two-dimensional NMR experiments, whereas their stability in solution was verified by UV–Vis spectroscopy. Interaction of complexes to ctDNA was investigated using UV–Vis and fluorescence emission spectroscopy. The minimum inhibitory concentration and the minimum microbicidal concentration values were detected against 15 bacterial strains and 4 yeast strains to examine the antimicrobial activity for the complexes. The in vitro antitumor properties of the complexes were studied by testing the complexes on leukemic cell line L1210, ovarian cancer cell line A2780 and non-cancerous cell line HEK293. The majority of the prepared compounds exhibited moderate antimicrobial and very high cytotoxic activity.
      Graphical abstract image

      PubDate: 2016-11-17T18:00:02Z
      DOI: 10.1016/j.jinorgbio.2016.11.021
       
  • Metagenomics analysis reveals a new metallothionein family: Sequence and
           metal-binding features of new environmental cysteine-rich proteins
    • Authors: Antoine Ziller; Rajiv Kumar Yadav; Mercè Capdevila; Mondem Sudhakara Reddy; Laurent Vallon; Roland Marmeisse; Silvia Atrian; Òscar Palacios; Laurence Fraissinet-Tachet
      Abstract: Publication date: Available online 12 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Antoine Ziller, Rajiv Kumar Yadav, Mercè Capdevila, Mondem Sudhakara Reddy, Laurent Vallon, Roland Marmeisse, Silvia Atrian, Òscar Palacios, Laurence Fraissinet-Tachet
      Metallothioneins are cysteine-rich proteins, which function as (i) metal carriers in basal cell metabolism and (ii) protective metal chelators in conditions of metal excess. Metallothioneins have been characterized from different eukaryotic model and cultivable species. Presently, they are categorized in 15 families but evolutionary relationships between these metallothionein families remain unresolved. Several cysteine-rich protein encoding genes that conferred Cd-tolerance in Cd-sensitive yeast mutants have previously been isolated from soil eukaryotic metatranscriptomes. They were called CRPs for “cysteine-rich proteins”. These proteins, of unknown taxonomic origins, share conserved cysteine motifs and could be considered as metallothioneins. In the present work, we analyzed these CRPs with respect to their amino acid sequence features and their metal-binding abilities towards Cd, Zn and Cu metal ions. Sequence analysis revealed that they share common features with different known metallothionein families, but also exhibit unique specific features. Noticeably, CRPs display two separate cysteine-rich domains which, when expressed separately in yeast, confer Cd-tolerance. The N-terminal domain contains some conserved atypical Cys motifs, such as one CCC and two CXCC ones. Five CRPs were expressed and purified as recombinant proteins and their metal-binding characteristics were studied. All these CRPs chelated Cd(II), Zn(II) and Cu(I), although displaying a better capacity for Zn(II) coordination. All CRPs are able to confer Cd-tolerance, and four of them confer Zn-tolerance in the Zn-sensitive zrc1Δ yeast mutant. We designated these CRPs as environmental metallothioneins belonging to a new formerly undescribed metallothionein family.
      Graphical abstract image

      PubDate: 2016-11-17T18:00:02Z
      DOI: 10.1016/j.jinorgbio.2016.11.017
       
  • Heterolytic OO bond cleavage: Functional role of Glu113 during Bis-Fe(IV)
           formation in MauG
    • Authors: Jiafeng Geng; Lu Huo; Aimin Liu
      Abstract: Publication date: Available online 9 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Jiafeng Geng, Lu Huo, Aimin Liu
      The diheme enzyme MauG utilizes H2O2 to perform oxidative posttranslational modification on a protein substrate. A bis-Fe(IV) species of MauG was previously identified as a key intermediate in this reaction. Heterolytic cleavage of the O-O bond of H2O2 drives the formation of the bis-Fe(IV) intermediate. In this work, we tested a hypothesis that a glutamate residue, Glu113 in the distal pocket of the pentacoordinate heme of MauG, facilitates heterolytic O-O bond cleavage, thereby leading to bis-Fe(IV) formation. This hypothesis was proposed based on sequence alignment and structural comparison with other H2O2-utilizing hemoenzymes, especially those from the diheme enzyme superfamily that MauG belongs to. Electron paramagnetic resonance characterization of the reaction between MauG and H2O2 revealed that mutation of Glu113 inhibited heterolytic O-O bond cleavage, in agreement with our hypothesis. This result was further confirmed by the HPLC study in which an analog of H2O2, cumene hydroperoxide, was used to probe the pattern of O-O bond cleavage. Together, our data suggest that Glu113 functions as an acid-base catalyst to assist heterolytic O-O bond cleavage during the early stage of the catalytic reaction. This work advances our mechanistic understanding of the H2O2-activation process during bis-Fe(IV) formation in MauG.

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.013
       
  • Heterolytic OO bond cleavage: Functional role of Glu113 during Bis-Fe(IV)
           formation in MauG
    • Authors: Jiafeng Geng; Lu Huo; Aimin Liu
      Abstract: Publication date: Available online 9 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Jiafeng Geng, Lu Huo, Aimin Liu
      The diheme enzyme MauG utilizes H2O2 to perform oxidative posttranslational modification on a protein substrate. A bis-Fe(IV) species of MauG was previously identified as a key intermediate in this reaction. Heterolytic cleavage of the O-O bond of H2O2 drives the formation of the bis-Fe(IV) intermediate. In this work, we tested a hypothesis that a glutamate residue, Glu113 in the distal pocket of the pentacoordinate heme of MauG, facilitates heterolytic O-O bond cleavage, thereby leading to bis-Fe(IV) formation. This hypothesis was proposed based on sequence alignment and structural comparison with other H2O2-utilizing hemoenzymes, especially those from the diheme enzyme superfamily that MauG belongs to. Electron paramagnetic resonance characterization of the reaction between MauG and H2O2 revealed that mutation of Glu113 inhibited heterolytic O-O bond cleavage, in agreement with our hypothesis. This result was further confirmed by the HPLC study in which an analog of H2O2, cumene hydroperoxide, was used to probe the pattern of O-O bond cleavage. Together, our data suggest that Glu113 functions as an acid-base catalyst to assist heterolytic O-O bond cleavage during the early stage of the catalytic reaction. This work advances our mechanistic understanding of the H2O2-activation process during bis-Fe(IV) formation in MauG.

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.013
       
  • Anticancer Copper Pyridine Benzimidazole Complexes: ROS Generation,
           Biomolecule Interactions, and Cytotoxicity
    • Authors: Kathleen E. Prosser; Stephanie W. Chang; Felix Saraci; Phúc H. Lê; Charles J. Walsby
      Abstract: Publication date: Available online 5 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Kathleen E. Prosser, Stephanie W. Chang, Felix Saraci, Phúc H. Lê, Charles J. Walsby
      The Cu(II) complex CuCl2(pbzH), pbzH = 2-(2-pyridinyl)benzimidazole, and derivatives modified at the non-coordinated nitrogen of the benzimidazole fragment, have been studied as anticancer agents. These compounds show promising cytotoxicity against A549 adenocarcinomic alveolar basal epithelial cells with IC50 values in the range of 5-10 μM. Importantly, this activity is higher than either CuCl2·H2O or the individual ligands, demonstrating that ligand coordination to the Cu(II) centres of the complexes is required for full activity. Electron paramagnetic resonance (EPR) and UV-Vis spectroscopies were used to characterize the solution behaviour of the complexes. These studies demonstrate: (i) two types of solvated species in buffer, (ii) both coordinate and non-coordinate interactions with albumin, and (iii) weak interactions with DNA. Further DNA studies using agarose gel electrophoresis demonstrate strand cleavage by the complexes in the presence of ascorbate, which is mediated by reactive oxygen species (ROS). Through a fluorescence-based in vitro assay, intracellular ROS generation in the A549 cell line was observed; indicating that damage by ROS is responsible for the observed activity of the complexes.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.006
       
  • Anticancer Copper Pyridine Benzimidazole Complexes: ROS Generation,
           Biomolecule Interactions, and Cytotoxicity
    • Authors: Kathleen E. Prosser; Stephanie W. Chang; Felix Saraci; Phúc H. Lê; Charles J. Walsby
      Abstract: Publication date: Available online 5 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Kathleen E. Prosser, Stephanie W. Chang, Felix Saraci, Phúc H. Lê, Charles J. Walsby
      The Cu(II) complex CuCl2(pbzH), pbzH = 2-(2-pyridinyl)benzimidazole, and derivatives modified at the non-coordinated nitrogen of the benzimidazole fragment, have been studied as anticancer agents. These compounds show promising cytotoxicity against A549 adenocarcinomic alveolar basal epithelial cells with IC50 values in the range of 5-10 μM. Importantly, this activity is higher than either CuCl2·H2O or the individual ligands, demonstrating that ligand coordination to the Cu(II) centres of the complexes is required for full activity. Electron paramagnetic resonance (EPR) and UV-Vis spectroscopies were used to characterize the solution behaviour of the complexes. These studies demonstrate: (i) two types of solvated species in buffer, (ii) both coordinate and non-coordinate interactions with albumin, and (iii) weak interactions with DNA. Further DNA studies using agarose gel electrophoresis demonstrate strand cleavage by the complexes in the presence of ascorbate, which is mediated by reactive oxygen species (ROS). Through a fluorescence-based in vitro assay, intracellular ROS generation in the A549 cell line was observed; indicating that damage by ROS is responsible for the observed activity of the complexes.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.006
       
 
 
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