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INORGANIC CHEMISTRY (41 journals)

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Acta Polymerica     Hybrid Journal   (Followers: 8)
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: 12)
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  
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: 8)
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: 14)
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  [3040 journals]
  • 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.
      Graphical abstract image

      PubDate: 2017-01-13T22:45:42Z
      DOI: 10.1016/j.jinorgbio.2016.10.001
      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.
      Graphical abstract image

      PubDate: 2017-01-13T22:45:42Z
      DOI: 10.1016/j.jinorgbio.2016.12.004
      Issue No: Vol. 168 (2017)
       
  • 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.
      Graphical abstract image

      PubDate: 2017-01-13T22:45:42Z
      DOI: 10.1016/j.jinorgbio.2017.01.001
       
  • 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.
      Graphical abstract image

      PubDate: 2017-01-05T22:15:30Z
      DOI: 10.1016/j.jinorgbio.2017.01.002
       
  • 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.
      Graphical abstract image

      PubDate: 2017-01-05T22:15:30Z
      DOI: 10.1016/j.jinorgbio.2017.01.004
       
  • 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.
      Graphical abstract image

      PubDate: 2017-01-05T22:15:30Z
      DOI: 10.1016/j.jinorgbio.2017.01.003
       
  • 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.
      Graphical abstract image

      PubDate: 2017-01-05T22:15:30Z
      DOI: 10.1016/j.jinorgbio.2017.01.005
       
  • 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.
      Graphical abstract image

      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.
      Graphical abstract image

      PubDate: 2016-12-21T11:50:33Z
      DOI: 10.1016/j.jinorgbio.2016.12.008
      Issue No: Vol. 168 (2016)
       
  • Enhancement of antibiotic-activity through complexation with metal ions -
           Combined ITC, NMR, enzymatic and biological studies
    • Authors: Jasper S. Möhler; Theresa Kolmar; Kevin Synnatschke; Marcel Hergert; Liam A. Wilson; Soumya Ramu; Alysha G. Elliott; Mark A.T. Blaskovich; Hanna E. Sidjabat; David L. Paterson; Gerhard Schenk; Matthew A. Cooper; Zyta M. Ziora
      Pages: 134 - 141
      Abstract: Publication date: February 2017
      Source:Journal of Inorganic Biochemistry, Volume 167
      Author(s): Jasper S. Möhler, Theresa Kolmar, Kevin Synnatschke, Marcel Hergert, Liam A. Wilson, Soumya Ramu, Alysha G. Elliott, Mark A.T. Blaskovich, Hanna E. Sidjabat, David L. Paterson, Gerhard Schenk, Matthew A. Cooper, Zyta M. Ziora
      Alternative solutions need to be developed to overcome the growing problem of multi-drug resistant bacteria. This study explored the possibility of creating complexes of antibiotics with metal ions, thereby increasing their activity. Analytical techniques such as isothermal titration calorimetry and nuclear magnetic resonance were used to examine the structure and interactions between Cu(II), Ag(I) or Zn(II) and β-lactam antibiotics. The metal-β-lactam complexes were also tested for antimicrobial activity, by micro-broth dilution and disk diffusion methods, showing a synergistic increase in the activity of the drugs, and enzymatic inhibition assays confirming inhibition of β-lactamases responsible for resistance. The metal-antibiotic complex concept was proven to be successful with the activity of the drugs enhanced against β-lactamase-producing bacteria. The highest synergistic effects were observed for complexes formed with Ag(I).
      Graphical abstract image

      PubDate: 2016-12-21T11:50:33Z
      DOI: 10.1016/j.jinorgbio.2016.11.028
      Issue No: Vol. 167 (2016)
       
  • Synthesis, characterization, and binding affinity of hydrosulfide
           complexes of synthetic iron(II) porphyrinates
    • Authors: Daniel J. Meininger; Hadi D. Arman; Zachary J. Tonzetich
      Pages: 142 - 149
      Abstract: Publication date: February 2017
      Source:Journal of Inorganic Biochemistry, Volume 167
      Author(s): Daniel J. Meininger, Hadi D. Arman, Zachary J. Tonzetich
      The binding and reactivity of the hydrosulfide ion (HS−) to iron(II) porphyrinates has been examined for several synthetic meso-tetraphenylporphine (TPP) derivatives. In all cases, HS− coordinates to the iron centers in a 1:1 stoichiometry with formation constants (K f) that reflect the electronic characteristics of the porphyrinate ligands. In the case of the F8TPP ligand (F8TPP=dianion of 5,10,15,20-tetrakis(2,6-difluorophenyl)porphine), an intermediate complex proposed as the hydrosulfide bridged dimer, (Bu4N)[Fe2(μ-SH)(F8TPP)2], was identified by NMR spectroscopy en route to formation of (Bu4N)[Fe(SH)(F8TPP)]. A robust procedure is reported for the synthesis and isolation of the parent hydrosulfide adduct, (Bu4N)[Fe(SH)(TPP)], which has permitted a detailed examination of its spectroscopy and chemical reactivity. Electrochemical measurements demonstrate that [Fe(SH)(TPP)]− is oxidized reversibly at a potential of −0.832V (vs ferrocene/ferrocenium) consistent with other iron porphyrinates containing sulfur-based ligands. Despite this fact, chemical oxidation of (Bu4N)[Fe(SH)(TPP)] with ferrocenium tetrafluoroborate produced only [Fe(TPP)] indicating that the putative iron(III) hydrosulfide adduct, [Fe(SH)(TPP)], decomposes rapidly. Treatment of (Bu4N)[Fe(SH)(TPP)] with other biologically relevant molecules such as NO and 1,2-dimethylimidazole resulted in simple displacement of the HS− ligand as governed by the relative K f values of the added ligands. The solid-state structure of one hydrosulfide adduct, (Bu4N)[Fe(SH)(F8TPP)], was determined by X-ray crystallography and found to display the expected five-coordinate geometry about iron with an Fe-S distance of 2.323(1) Å. The relevance of the hydrosulfide chemistry with synthetic iron porphyrinates is discussed in terms of the possible reactivity for H2S and its derivatives at heme sites in biology.
      Graphical abstract image

      PubDate: 2016-12-28T13:46:41Z
      DOI: 10.1016/j.jinorgbio.2016.08.014
      Issue No: Vol. 167 (2016)
       
  • Crucial residue Trp158 of lipoprotein PiaA stabilizes the ferrichrome-PiaA
           complex in Streptococcus pneumoniae
    • Authors: Liang Zhang; Nan Li; Kun Cao; Xiao-Yan Yang; Guandi Zeng; Xuesong Sun; Qing-Yu He
      Pages: 150 - 156
      Abstract: Publication date: February 2017
      Source:Journal of Inorganic Biochemistry, Volume 167
      Author(s): Liang Zhang, Nan Li, Kun Cao, Xiao-Yan Yang, Guandi Zeng, Xuesong Sun, Qing-Yu He
      The pathogenic Streptococcus pneumoniae (S. pneumoniae) has evolved a special mechanism such as pneumococcal iron acquisition ATP binding cassette (PiaABC) to take up siderophore-iron from its host. The cell-surface lipoprotein PiaA, a key component of PiaABC, is the primary receptor to bind ferrichrome (Fc). To study the structure-function relationship of PiaA, three conservative amino-acid residues, Trp63, Trp158 and Phe255, in the hydrophobic barrel of the metal binding site of PiaA, were individually and collectively mutated to alanine; and the resulted single-point mutants, W63A, W158A and F255A, and triple mutant W63A/W158A/F255A were characterized by using biochemical and biophysical methods. Experiments showed that wild-type PiaA (WT-PiaA) and the single-point mutant proteins bound Fc with a similar kinetics mode, but the reaction rate of W158A was lower than that for WT-PiaA. The binding affinity of W158A toward Fc was significantly weaker than that of the WT-PiaA-Fc (wild-type PiaA bound with Fc) interaction. Furthermore, the absence of Trp158 in the protein led to a significant impact on the secondary structure of PiaA, resulting in a labile conformational structure of W158A, with impaired resistance to thermal and chemical denaturation. Collectively, Trp158 is a crucial residue for binding Fc, playing an important role in stabilizing the PiaA-Fc complex. This study revealed the critical role of the conserved tryptophan residues in Fc-binding protein PiaA, and provided valuable information for understanding the Fc transport mechanism mediated by PiaA or its homologous proteins in bacteria.
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      PubDate: 2016-12-28T13:46:41Z
      DOI: 10.1016/j.jinorgbio.2016.08.015
      Issue No: Vol. 167 (2016)
       
  • Ru(III) anticancer agents with aromatic and non-aromatic dithiocarbamates
           asligands: Loading into nanocarriers and preliminary biological studies
    • Authors: S. Scintilla; L. Brustolin; A. Gambalunga; F. Chiara; A. Trevisan; C. Nardon; D. Fregona
      Pages: 76 - 86
      Abstract: Publication date: January 2017
      Source:Journal of Inorganic Biochemistry, Volume 166
      Author(s): S. Scintilla, L. Brustolin, A. Gambalunga, F. Chiara, A. Trevisan, C. Nardon, D. Fregona


      PubDate: 2016-11-17T18:00:02Z
      DOI: 10.1016/j.jinorgbio.2016.09.009
      Issue No: Vol. 166 (2016)
       
  • 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
       
  • 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
       
  • 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
       
  • 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
       
  • 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
       
  • Sequestering ability to Cu2+ of a new bodipy-based dye and its behavior as
           in vitro fluorescent sensor
    • Authors: Teresa Papalia; Anna Barattucci; Davide Barreca; Ersilia Bellocco; Paola Bonaccorsi; Lucio Minuti; Marco Sebastiano Nicolò; Andrea Temperini; Claudia Foti
      Abstract: Publication date: Available online 2 December 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Teresa Papalia, Anna Barattucci, Davide Barreca, Ersilia Bellocco, Paola Bonaccorsi, Lucio Minuti, Marco Sebastiano Nicolò, Andrea Temperini, Claudia Foti
      A Bodipy (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) derivative has been conceived and synthesized starting from l-aspartic acid, as a selective turn-off sensor of Cu2+ ions. Its acid–base properties were determined to study the formation of metal/sensor complex species by titration of solutions each containing a different metal ion, such as Cu2+, Ca2+, Zn2+, Pb2+ and Hg2+ and different metal/sensor ratios. The speciation models allowed us to simulate the distribution of the metal/sensor complex species at the normal concentrations of the corresponding metals present in biological fluids. The distribution diagrams, obtained by varying the concentration of sensor 1, clearly indicate that sensor 1 responds selectively to Cu2+ at micromolar concentrations, even in the presence of other more abundant metal cations Ca2+. Finally, we analyzed the cellular uptake of sensor 1 on human erythrocytes and its ability to chelate Cu2+ in the cellular environment. Results indicate that it crosses the plasmatic membrane and colors the cells of a bright fluorescent red. Exposing the fluorescent cells to Cu2+ results in a complete cellular photobleaching of the red fluorescence, indicating that sensor 1 is able to detect metal changes in the cytosolic environment.
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      PubDate: 2016-12-06T11:14:51Z
      DOI: 10.1016/j.jinorgbio.2016.11.030
       
  • Challenges in assignment of allosteric effects in cytochrome
           P450-catalyzed substrate oxidations to structural dynamics in the
           hemoprotein architecture
    • Authors: Peter Hlavica
      Abstract: Publication date: Available online 25 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Peter Hlavica
      Cytochrome P450s (CYP) represent a superfamily of b-type hemoproteins catalyzing NAD(P)H-dependent oxidative biotransformation of a vast array of natural and xenobiotic compounds. Many eu- and prokaryotic members of this class of monooxygenases display complex non-Michaelis-Menten saturation kinetics, suggestive of homo-/heterotropic cooperativity arising from substrate-/effector-induced allosteric interactions. Here, the paradigm of multiple-ligand occupancy of the catalytic pocket in combination with enzyme oligomerization provides the most favored explanations for the atypical kinetic patterns. Making use of available data from crystallographic analyses, homology modeling and site-directed mutagenesis, the present review focuses on assessment of the topology of prospective key players dictating allosterism. Based on a general, CYP3A4-related construct, the majority of determinants were found to cluster within the six known substrate recognition sites (SRSs). Here, the B′/B′-C domains (SRS-1) and the F-helical region (SRS-2) harbor 51% of the critical residues, while SRS-4/5/6 each accommodate about 11–17% of the presumed docking spots. Of note, 12% of the total number of functional amino acids resides in non-SRS motifs. Average frequency of conservation of the allosteric sites examined was found to be fairly low (~13%), hinting at the requirement of some degree of conformational flexibility. Reactivity toward ligands coincides with the lipophilicity/hydrophilicity profile and bulkiness of the elements acting as selective filters. In sum, cooperative scenarios mainly pertain to regulative effects on substrate ingress, tuning of the open/closed equilibrium of the substrate access channel, modulation of the active-site capacity and productive ligand orientation toward the iron-oxene core. Deeper insight into the molecular mechanism of allostery may help avoid undesired drug-drug interplay in medicinal therapy and offer detoxification response to toxic agents. Finally, genetic manipulation of the cooperative machinery of P450s may provide a powerful tool in drug development.
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      PubDate: 2016-11-29T18:33:42Z
      DOI: 10.1016/j.jinorgbio.2016.11.025
       
  • 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
       
  • 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
       
  • 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
       
  • 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
       
  • 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
       
  • Characterization of the second conserved domain in the heme uptake protein
           HtaA from Corynebacterium diphtheriae
    • Authors: Rizvan C. Uluisik; Neval Akbas; Gudrun S. Lukat-Rodgers; Seth A. Adrian; Courtni E. Allen; Michael P. Schmitt; Kenton R. Rodgers; Dabney W. Dixon
      Abstract: Publication date: Available online 23 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Rizvan C. Uluisik, Neval Akbas, Gudrun S. Lukat-Rodgers, Seth A. Adrian, Courtni E. Allen, Michael P. Schmitt, Kenton R. Rodgers, Dabney W. Dixon
      HtaA is a heme-binding protein that is part of the heme uptake system in Corynebacterium diphtheriae. HtaA contains two conserved regions (CR1 and CR2). It has been previously reported that both domains can bind heme; the CR2 domain binds hemoglobin more strongly than the CR1 domain. In this study, we report the biophysical characteristics of HtaA-CR2. UV–visible spectroscopy and resonance Raman experiments are consistent with this domain containing a single heme that is bound to the protein through an axial tyrosine ligand. Mutants of conserved tyrosine and histidine residues (Y361, H412, and Y490) have been studied. These mutants are isolated with very little heme (≤ 5%) in comparison to the wild-type protein (~20%). Reconstitution after removal of the heme with butanone gave an alternative form of the protein. The HtaA-CR2 fold is very stable; it was necessary to perform thermal denaturation experiments in the presence of guanidinium hydrochloride. HtaA-CR2 unfolds extremely slowly; even in 6.8M GdnHCl at 37°C, the half-life was 5h. In contrast, the apo forms of WT HtaA-CR2 and the aforementioned mutants unfolded at much lower concentrations of GdnHCl, indicating the role of heme in stabilizing the structure and implying that heme transfer is effected only to a partner protein in vivo.
      Graphical abstract image

      PubDate: 2016-11-23T18:12:00Z
      DOI: 10.1016/j.jinorgbio.2016.11.027
       
  • 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
       
  • 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
       
  • 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.
      Graphical abstract image

      PubDate: 2016-11-17T18:00:02Z
      DOI: 10.1016/j.jinorgbio.2016.11.023
       
  • Synthesis of Ag(I) camphor sulphonylimine complexes and assessment of
           their cytotoxic properties against cisplatin-resistant A2780cisR and A2780
           cell lines
    • Authors: João M.S. Cardoso; Isabel Correia; Adelino M. Galvão; Fernanda Marques; M. Fernanda N.N. Carvalho
      Abstract: Publication date: Available online 4 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): João M.S. Cardoso, Isabel Correia, Adelino M. Galvão, Fernanda Marques, M. Fernanda N.N. Carvalho
      Camphorsulphonylimine complexes [Ag(NO3)(IL)2] (IL=C12H19N3SO2, 1) and [(AgNO3)2(IIL)] (IIL=C22H23N3SO2, 2) were synthesized and characterized by elemental analysis, spectroscopy (IR, NMR) and cyclic voltammetry. [Ag(NO3)(IL)2] crystalizes in the monoclinic C2 space group with a triangular geometry assuming a chalice-type shape. The anti-proliferative properties of the new complexes 1 and 2 and those of the previously reported [(AgNO3)2(IIIL)] (IIIL=C16H18N3SO2, 3) were assessed against the human ovarian cancer cells (cisplatin-sensitive A2780, cisplatin-resistant A2780cisR) and the non-tumoral human HEK 293 cell line, using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The NR (3-amino-7-dimethylamino-2-methylphenazine hydrochloride) assay was alternatively used to assess the cytotoxicity on the A2780 cells. Results from the MTT assay (48h exposure) show that the complexes display IC50 values lower (by at least one order of magnitude) than cisplatin, while the cytotoxicity of AgNO3 is of the same order of cisplatin. The camphorsulphonylimine ligands display irrelevant (IL, IIIL) or no cytotoxicity (IIL). The highest cytotoxicity (lower IC50) was found for [(AgNO3)2(IIL)]. The binding ability of the complexes to calf thymus-deoxyribonucleic acid (CT-DNA) was studied by fluorescence. Constants (Ksv, Ka) and the number (n) of binding centres to DNA were calculated showing that DNA intercalation possibly occurs in the cases of complexes 2 and 3, while a more complicated process operates for 1. As expected from the cytotoxicity, [(AgNO3)2(IIL)] displays the highest binding affinity (Ka =1.61×105 M−1). No binding to DNA was detected for AgNO3 or IIL under the experimental conditions used. The binding trend to CT-DNA found by fluorescence was corroborated by cyclic voltammetry.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.003
       
  • Synthesis of Ag(I) camphor sulphonylimine complexes and assessment of
           their cytotoxic properties against cisplatin-resistant A2780cisR and A2780
           cell lines
    • Authors: João M.S. Cardoso; Isabel Correia; Adelino M. Galvão; Fernanda Marques; M. Fernanda N.N. Carvalho
      Abstract: Publication date: Available online 4 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): João M.S. Cardoso, Isabel Correia, Adelino M. Galvão, Fernanda Marques, M. Fernanda N.N. Carvalho
      Camphorsulphonylimine complexes [Ag(NO3)(IL)2] (IL=C12H19N3SO2, 1) and [(AgNO3)2(IIL)] (IIL=C22H23N3SO2, 2) were synthesized and characterized by elemental analysis, spectroscopy (IR, NMR) and cyclic voltammetry. [Ag(NO3)(IL)2] crystalizes in the monoclinic C2 space group with a triangular geometry assuming a chalice-type shape. The anti-proliferative properties of the new complexes 1 and 2 and those of the previously reported [(AgNO3)2(IIIL)] (IIIL=C16H18N3SO2, 3) were assessed against the human ovarian cancer cells (cisplatin-sensitive A2780, cisplatin-resistant A2780cisR) and the non-tumoral human HEK 293 cell line, using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The NR (3-amino-7-dimethylamino-2-methylphenazine hydrochloride) assay was alternatively used to assess the cytotoxicity on the A2780 cells. Results from the MTT assay (48h exposure) show that the complexes display IC50 values lower (by at least one order of magnitude) than cisplatin, while the cytotoxicity of AgNO3 is of the same order of cisplatin. The camphorsulphonylimine ligands display irrelevant (IL, IIIL) or no cytotoxicity (IIL). The highest cytotoxicity (lower IC50) was found for [(AgNO3)2(IIL)]. The binding ability of the complexes to calf thymus-deoxyribonucleic acid (CT-DNA) was studied by fluorescence. Constants (Ksv, Ka) and the number (n) of binding centres to DNA were calculated showing that DNA intercalation possibly occurs in the cases of complexes 2 and 3, while a more complicated process operates for 1. As expected from the cytotoxicity, [(AgNO3)2(IIL)] displays the highest binding affinity (Ka =1.61×105 M−1). No binding to DNA was detected for AgNO3 or IIL under the experimental conditions used. The binding trend to CT-DNA found by fluorescence was corroborated by cyclic voltammetry.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.003
       
  • Structural characteristics of amorphous K-Bi citrate (De-Nol) and its
           aqueous solutions from EXAFS spectra
    • Authors: Simon B. Erenburg; Svetlana V. Trubina; Yuri M. Yukhin; Marat R. Sharafutdinov
      Abstract: Publication date: Available online 4 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Simon B. Erenburg, Svetlana V. Trubina, Yuri M. Yukhin, Marat R. Sharafutdinov
      EXAFS (Extended X-ray Absorption Fine Structure) spectra of an amorphous solid Bi complex with citrate (known as De-Nol) and its aqueous solutions in a wide concentration range are measured. For the solutions good agreement is revealed between their structural parameters and the averaged interatomic distances and coordination numbers of the crystalline polymeric bismuth citrate compound composed of 12-nuclear Bi clusters based on the structure Bi12O22. So, it is found that droplets of the colloidal solution have a core structure close to the solid Bi12O22 cluster structure. When the concentrated solution is diluted the cluster structure is somewhat modified, it remaining similar to the structure of the Bi12O22 cluster and even at a tenfold dilution and the nearest (oxygen) spheres of the Bi environment changing insignificantly. The appearance in this case of an additional oxygen atom at a large distance from the bismuth atom likely due to the presence of the oxygen atom from the hydroxyl group of the diluted aqueous solution. The appearance of such oxygen is in accordance with particles size increase for diluted solution obtained by small-angle X-ray diffraction measurements. It is established that the structure of the amorphous solid complex is multiphase and, as a whole, similar to the structure of the solid binuclear complexes.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.001
       
  • Structural characteristics of amorphous K-Bi citrate (De-Nol) and its
           aqueous solutions from EXAFS spectra
    • Authors: Simon B. Erenburg; Svetlana V. Trubina; Yuri M. Yukhin; Marat R. Sharafutdinov
      Abstract: Publication date: Available online 4 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Simon B. Erenburg, Svetlana V. Trubina, Yuri M. Yukhin, Marat R. Sharafutdinov
      EXAFS (Extended X-ray Absorption Fine Structure) spectra of an amorphous solid Bi complex with citrate (known as De-Nol) and its aqueous solutions in a wide concentration range are measured. For the solutions good agreement is revealed between their structural parameters and the averaged interatomic distances and coordination numbers of the crystalline polymeric bismuth citrate compound composed of 12-nuclear Bi clusters based on the structure Bi12O22. So, it is found that droplets of the colloidal solution have a core structure close to the solid Bi12O22 cluster structure. When the concentrated solution is diluted the cluster structure is somewhat modified, it remaining similar to the structure of the Bi12O22 cluster and even at a tenfold dilution and the nearest (oxygen) spheres of the Bi environment changing insignificantly. The appearance in this case of an additional oxygen atom at a large distance from the bismuth atom likely due to the presence of the oxygen atom from the hydroxyl group of the diluted aqueous solution. The appearance of such oxygen is in accordance with particles size increase for diluted solution obtained by small-angle X-ray diffraction measurements. It is established that the structure of the amorphous solid complex is multiphase and, as a whole, similar to the structure of the solid binuclear complexes.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.001
       
  • Genotoxic assessment of the copper chelated compounds Casiopeinas: Clues
           about their mechanisms of action
    • Authors: Jorge Serment-Guerrero; Maria Elena Bravo-Gomez; Eric Lara-Rivera; Lena Ruiz-Azuara
      Abstract: Publication date: Available online 5 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Jorge Serment-Guerrero, Maria Elena Bravo-Gomez, Eric Lara-Rivera, Lena Ruiz-Azuara
      Casiopeinas is the generic name of a group of copper chelated complexes designed to be used as antineoplastic. Some of these compounds have shown promising results, and in fact, one of them named Casiopeina III-ia has completed preclinical trials and is ready to start clinical phase I in Mexico. As part of the tests that have to be done to every molecule intended to be used in humans, bacterial assays are required because of their sensitivity, speed and reproducibility and among them, Ames test and the SOS Chromotest are widely used to evaluate DNA damage. With the aim to contribute to complete safety information related to genotoxicity and support the hypothesis about their mode of action, four different Casiopeinas (Cas II-gly, Cas III-Ea, Cas III-ia and Cas III-Ha) were tested for genotoxicity with these assays, as well as differential cytotoxicity upon Escherichia coli mutants defectives in some DNA repair mechanisms. However, although it is well known that these molecules produce DNA breakage, the results of the Chromotest and Ames test were negative. Despite this is controversial, a possible explanation is that there is a direct interaction between DNA and the Casiopeinas tested.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.007
       
  • Genotoxic assessment of the copper chelated compounds Casiopeinas: Clues
           about their mechanisms of action
    • Authors: Jorge Serment-Guerrero; Maria Elena Bravo-Gomez; Eric Lara-Rivera; Lena Ruiz-Azuara
      Abstract: Publication date: Available online 5 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Jorge Serment-Guerrero, Maria Elena Bravo-Gomez, Eric Lara-Rivera, Lena Ruiz-Azuara
      Casiopeinas is the generic name of a group of copper chelated complexes designed to be used as antineoplastic. Some of these compounds have shown promising results, and in fact, one of them named Casiopeina III-ia has completed preclinical trials and is ready to start clinical phase I in Mexico. As part of the tests that have to be done to every molecule intended to be used in humans, bacterial assays are required because of their sensitivity, speed and reproducibility and among them, Ames test and the SOS Chromotest are widely used to evaluate DNA damage. With the aim to contribute to complete safety information related to genotoxicity and support the hypothesis about their mode of action, four different Casiopeinas (Cas II-gly, Cas III-Ea, Cas III-ia and Cas III-Ha) were tested for genotoxicity with these assays, as well as differential cytotoxicity upon Escherichia coli mutants defectives in some DNA repair mechanisms. However, although it is well known that these molecules produce DNA breakage, the results of the Chromotest and Ames test were negative. Despite this is controversial, a possible explanation is that there is a direct interaction between DNA and the Casiopeinas tested.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.007
       
  • Synthesis and antibacterial activity of silver@carbon nanocomposites
    • Authors: Kunjie Wang; Qingjuan Ji; Hongxia Li; Feng Guan; Deyi Zhang; Huixia Feng; Haiyan Fan
      Abstract: Publication date: Available online 5 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Kunjie Wang, Qingjuan Ji, Hongxia Li, Feng Guan, Deyi Zhang, Huixia Feng, Haiyan Fan
      In this work, hollow multiple-Ag-nanoclustes- C-shell nanocomposites (Ag@C) were synthesized by using silane coupling agent to graft carbon dots(CDs) with silver nanoparticles(AgNPs). CDs act as coating and stabilizing agent, protecting AgNPs from aggregation and oxidation. And the results indicated that Ag@C nanocomposites demonstrate strong bactericidal effect on both gram-negative and gram-positive bacteria that were tested by the disk diffusion method. Cellular toxicity evaluation was performed using MTT assay. Meanwhile, the as-prepared Ag@C nanocomposites show a good biocompatibility.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.002
       
  • Synthesis and antibacterial activity of silver@carbon nanocomposites
    • Authors: Kunjie Wang; Qingjuan Ji; Hongxia Li; Feng Guan; Deyi Zhang; Huixia Feng; Haiyan Fan
      Abstract: Publication date: Available online 5 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Kunjie Wang, Qingjuan Ji, Hongxia Li, Feng Guan, Deyi Zhang, Huixia Feng, Haiyan Fan
      In this work, hollow multiple-Ag-nanoclustes- C-shell nanocomposites (Ag@C) were synthesized by using silane coupling agent to graft carbon dots(CDs) with silver nanoparticles(AgNPs). CDs act as coating and stabilizing agent, protecting AgNPs from aggregation and oxidation. And the results indicated that Ag@C nanocomposites demonstrate strong bactericidal effect on both gram-negative and gram-positive bacteria that were tested by the disk diffusion method. Cellular toxicity evaluation was performed using MTT assay. Meanwhile, the as-prepared Ag@C nanocomposites show a good biocompatibility.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.002
       
  • 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
       
  • Inorganic mesoporous silicas as vehicles of two novel anthracene-based
           ruthenium metalloarenes
    • Authors: Sara Rojas; Francisco J. Carmona; Elisa Barea; Carmen R. Maldonado
      Abstract: Publication date: Available online 7 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Sara Rojas, Francisco J. Carmona, Elisa Barea, Carmen R. Maldonado
      Two novel anthracene-based half-sandwich organometallic Ru(II) compounds, namely, [Ru(p-cymene)(L1)Cl2] (1) and [Ru(p-cymene)(L2)Cl2] (2) (L 1 =1-(anthracen-9-yl)-N-(pyridin-3-ylmethyl)methanamine; L 2 =1-(anthracen-9-yl)-N-(pyridin-4-ylmethyl)methanamine) have been synthesized and characterized. We demonstrate that the fluorescence properties of these complexes are highly affected by the linking position of the anthracene unit, as only 2 shows fluorescence emission in the blue region. Regarding their biological activity, both ruthenium metallodrugs show interaction with different biological targets such as S-donor aminoacids (cysteine) and proteases (cysteine cathepsin B). Moreover, 1 and 2 show in vitro cytotoxicity against HL-60 cancer cell line (IC50 =84.5 and 87.0μM for 1 and 2, respectively), with cell death occurring via apoptosis. Further studies have shown that diffusion into cells is the main mechanism of metallodrug uptake. Finally, as a proof of concept, these ruthenium complexes have been succesfully encapsulated into MCM-41 and SBA-15 mesoporous silicas using two different incorporation strategies (impregnation and grinding).
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.004
       
  • Inorganic mesoporous silicas as vehicles of two novel anthracene-based
           ruthenium metalloarenes
    • Authors: Sara Rojas; Francisco J. Carmona; Elisa Barea; Carmen R. Maldonado
      Abstract: Publication date: Available online 7 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Sara Rojas, Francisco J. Carmona, Elisa Barea, Carmen R. Maldonado
      Two novel anthracene-based half-sandwich organometallic Ru(II) compounds, namely, [Ru(p-cymene)(L1)Cl2] (1) and [Ru(p-cymene)(L2)Cl2] (2) (L 1 =1-(anthracen-9-yl)-N-(pyridin-3-ylmethyl)methanamine; L 2 =1-(anthracen-9-yl)-N-(pyridin-4-ylmethyl)methanamine) have been synthesized and characterized. We demonstrate that the fluorescence properties of these complexes are highly affected by the linking position of the anthracene unit, as only 2 shows fluorescence emission in the blue region. Regarding their biological activity, both ruthenium metallodrugs show interaction with different biological targets such as S-donor aminoacids (cysteine) and proteases (cysteine cathepsin B). Moreover, 1 and 2 show in vitro cytotoxicity against HL-60 cancer cell line (IC50 =84.5 and 87.0μM for 1 and 2, respectively), with cell death occurring via apoptosis. Further studies have shown that diffusion into cells is the main mechanism of metallodrug uptake. Finally, as a proof of concept, these ruthenium complexes have been succesfully encapsulated into MCM-41 and SBA-15 mesoporous silicas using two different incorporation strategies (impregnation and grinding).
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.004
       
  • Nanosized mesoporous metal–organic framework MIL-101 as a nanocarrier
           for photoactive hexamolybdenum cluster compounds
    • Authors: Anastasia M. Cheplakova; Anastasiya O. Solovieva; Tatiana N. Pozmogova; Yuri A. Vorotnikov; Konstantin A. Brylev; Natalya A. Vorotnikova; Elena V. Vorontsova; Yuri V. Mironov; Alexander F. Poveshchenko; Konstantin A. Kovalenko; Michael A. Shestopalov
      Abstract: Publication date: Available online 9 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Anastasia M. Cheplakova, Anastasiya O. Solovieva, Tatiana N. Pozmogova, Yuri A. Vorotnikov, Konstantin A. Brylev, Natalya A. Vorotnikova, Elena V. Vorontsova, Yuri V. Mironov, Alexander F. Poveshchenko, Konstantin A. Kovalenko, Michael A. Shestopalov
      Inclusion compounds of photoluminescent hexamolybdenum cluster complexes in the chromium terephthalate metal-organic framework, MIL-101 (MIL, Matérial Institut Lavoisier) were successfully synthesized in two different ways and characterized by means of powder X-Ray diffraction, chemical analysis and nitrogen sorption. Some important functional properties of hexamolybdenum cluster complexes for biological and medical applications, in particular singlet oxygen generation ability, luminescence properties, cellular uptake behavior and cytotoxicity were studied. It was revealed that the inclusion compounds possessed significant singlet oxygen generation activity. The materials obtained showed a low cytotoxicity, thus allowing them to be used in living cells. Confocal microscopy of human larynx carcinoma (Hep-2) cells incubated with the inclusion compounds showed that MIL-101 performed as a nanocarrier adhering to the external cell membrane surface and releasing the cluster complexes which that penetrated into the cells. Moreover, photoinduced generation of reactive oxygen species (ROS) in Hep-2 cells incubated with inclusion compounds was demonstrated. The cluster supported on MIL-101 was shown to possess in vivo phototoxicity.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.014
       
  • Nanosized mesoporous metal–organic framework MIL-101 as a nanocarrier
           for photoactive hexamolybdenum cluster compounds
    • Authors: Anastasia M. Cheplakova; Anastasiya O. Solovieva; Tatiana N. Pozmogova; Yuri A. Vorotnikov; Konstantin A. Brylev; Natalya A. Vorotnikova; Elena V. Vorontsova; Yuri V. Mironov; Alexander F. Poveshchenko; Konstantin A. Kovalenko; Michael A. Shestopalov
      Abstract: Publication date: Available online 9 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Anastasia M. Cheplakova, Anastasiya O. Solovieva, Tatiana N. Pozmogova, Yuri A. Vorotnikov, Konstantin A. Brylev, Natalya A. Vorotnikova, Elena V. Vorontsova, Yuri V. Mironov, Alexander F. Poveshchenko, Konstantin A. Kovalenko, Michael A. Shestopalov
      Inclusion compounds of photoluminescent hexamolybdenum cluster complexes in the chromium terephthalate metal-organic framework, MIL-101 (MIL, Matérial Institut Lavoisier) were successfully synthesized in two different ways and characterized by means of powder X-Ray diffraction, chemical analysis and nitrogen sorption. Some important functional properties of hexamolybdenum cluster complexes for biological and medical applications, in particular singlet oxygen generation ability, luminescence properties, cellular uptake behavior and cytotoxicity were studied. It was revealed that the inclusion compounds possessed significant singlet oxygen generation activity. The materials obtained showed a low cytotoxicity, thus allowing them to be used in living cells. Confocal microscopy of human larynx carcinoma (Hep-2) cells incubated with the inclusion compounds showed that MIL-101 performed as a nanocarrier adhering to the external cell membrane surface and releasing the cluster complexes which that penetrated into the cells. Moreover, photoinduced generation of reactive oxygen species (ROS) in Hep-2 cells incubated with inclusion compounds was demonstrated. The cluster supported on MIL-101 was shown to possess in vivo phototoxicity.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.014
       
  • 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
       
  • Copper (II) complexes possessing alkyl-substituted polypyridyl ligands:
           Structural characterization and in vitro antitumor activity
    • Authors: Noah Angel; Raneen Khatib Julia Jenkins Michelle Smith Justin Rubalcava
      Abstract: Publication date: Available online 22 October 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Noah R. Angel, Raneen M. Khatib, Julia Jenkins, Michelle Smith, Justin M. Rubalcava, Brian Khoa Le, Daniel Lussier, Zhuo (Georgia) Chen, Fook S. Tham, Emma H. Wilson, Jack F. Eichler
      In an effort to find alternatives to the antitumor drug cisplatin, a series of copper (II) complexes possessing alkyl-substituted polypyridyl ligands have been synthesized. Eight new complexes are reported herein: μ-dichloro-bis{2,9-di-sec-butyl-1,10-phenanthrolinechlorocopper(II)} {[(di-sec-butylphen)ClCu(μ-Cl)2CuCl(di-sec-butylphen)]}(1), 2-sec-butyl-1,10-phenanthrolinedichlorocopper(II) {[mono-sec-butylphen) CuCl2} (2), 2,9-di-n-butyl-1,10-phenanthrolinedichlorocopper(II) {[di-n-butylphen) CuCl2}(3), 2-n-butyl-1,10-phenanthrolinedichlorocopper(II) {[mono-n-butylphen) CuCl2} (4), 2,9-di-methyl-1,10-phenanthrolineaquadichlorocopper(II) {[di-methylphen) Cu(H2O)Cl2}(5), μ-dichloro-bis{6-sec-butyl-2,2′-bipyridinedichlorocopper(II)} {(mono-sec-butylbipy) ClCu(μ-Cl)2CuCl(mono-sec-butylbipy)} (6), 6,6′-di-methyl-2,2′-bipyridinedichlorocopper(II) {6,6′-di-methylbipy) CuCl2} (7), and 4,4′-dimethyl-2,2′-bipyridinedichlorocopper(II) {4,4′-di-methylbipy) CuCl2} (8). These complexes have been characterized via elemental analysis, UV–vis spectroscopy, and mass spectrometry. Single crystal X-ray diffraction experiments revealed the complexes synthesized with the di-sec-butylphen ligand (1) and mono-sec-butylbipy ligand (6) crystallized as dimers in which two copper(II) centers are bridged by two chloride ligands. Conversely, complexes 2, 7, and 8 were isolated as monomeric species possessing distorted tetrahedral geometries, and the [(di-methylphen)Cu(H2O)Cl2] (5) complex was isolated as a distorted square pyramidal monomer possessing a coordinating aqua ligand. Compounds 1–8 were evaluated for their in vitro antitumor efficacy. Compounds 1, 5, and 7 in particular were found to exhibit remarkable activity against human derived lung cancer cells, yet this class of copper(II) compounds had minimal cytotoxic effect on non-cancerous cells. In vitro control experiments indicate the activity of the copper(II) complexes most likely does not arise from the formation of CuCl2 and free polypyridyl ligand, and preliminary solution state studies suggest these compounds are generally stable in biological buffer. The results presented herein suggest further development of this class of copper-based drugs as potential anti-cancer therapies should be pursued.
      Graphical abstract image

      PubDate: 2016-10-27T23:08:05Z
       
  • The facial triad in the α-ketoglutarate dependent oxygenase FIH: A role
           for sterics in linking substrate binding to O2 activation
    • Authors: John A. Hangasky; Cornelius Y. Taabazuing; Cristina B. Martin; Scott J. Eron; Michael J. Knapp
      Abstract: Publication date: Available online 17 October 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): John A. Hangasky, Cornelius Y. Taabazuing, Cristina B. Martin, Scott J. Eron, Michael J. Knapp
      The factor inhibiting hypoxia inducible factor-1α (FIH) is a nonheme Fe(II)/αKG oxygenase using a 2-His-1-Asp facial triad. FIH activates O2 via oxidative decarboxylation of α-ketoglutarate (αKG) to generate an enzyme-based oxidant which hydroxylates the Asn803 residue within the C-terminal transactivation domain (CTAD) of HIF-1α. Tight coupling of these two sequential reactions requires a structural linkage between the Fe(II) and the substrate binding site to ensure that O2 activation occurs after substrate binds. We tested the hypothesis that the facial triad carboxylate (Asp201) of FIH linked substrate binding and O2 binding sites. Asp201 variants of FIH were constructed and thoroughly characterized in vitro using steady-state kinetics, crystallography, autohydroxylation, and coupling measurements. Our studies revealed each variant activated O2 with a catalytic efficiency similar to that of wild-type (WT) FIH (k cat aK M(O2) =0.17μM−1min−1), but led to defects in the coupling of O2 activation to substrate hydroxylation. Steady-state kinetics showed similar catalytic efficiencies for hydroxylation by WT-FIH (k cat /K M(CTAD) =0.42μM−1 min−1) and D201G (k cat /K M(CTAD) =0.34μM−1 min−1); hydroxylation by D201E was greatly impaired, while hydroxylation by D201A was undetectable. Analysis of the crystal structure of the D201E variant revealed steric crowding near the diffusible ligand site supporting a role for sterics from the facial triad carboxylate in the O2 binding order. Our data support a model in which the facial triad carboxylate Asp201 provides both steric and polar contacts to favor O2 access to the Fe(II) only after substrate binds, leading to coupled turnover in FIH and other αKG oxygenases.
      Graphical abstract image

      PubDate: 2016-10-22T18:23:31Z
      DOI: 10.1016/j.jinorgbio.2016.10.007
       
  • Nitrite coordination in myoglobin
    • Authors: Androulla Ioannou; Alexandra Lambrou Vangelis Daskalakis Eftychia Pinakoulaki
      Abstract: Publication date: Available online 14 October 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Androulla Ioannou, Alexandra Lambrou, Vangelis Daskalakis, Eftychia Pinakoulaki
      The coordination of nitrite in myoglobin (Mb) has been characterized by resonance Raman spectroscopy and the frequencies of the nitrite bound to the heme Fe as well to the 2-vinyl have been computed by Density Functional Theory (DFT) calculations. The DFT Natural Bond Orbital (NBO) analysis and the extensive isotope-labeling in the resonance Raman experiments indicate that NO2 − (O1-N=O2) is bound to the heme Fe via O1. Based on the vibrational characterization of the reversible transition between low and high spin Fe-O-N=O/2-nitrovinyl species, we suggest that the key step that triggers the spin-change is the increase of the proximal Fe-NHis93 bond length. The frequencies of the O and N sensitive bands of the Fe-O-N=O/2-nitrovinyl species remained largely unchanged in the low-to high-spin transition. Therefore the “greening” process in the reaction of ferric Mb with NO2 − proceeds through the Fe-O-N=O/2-nitrovinyl species, which can exist in either the high or low-spin state.
      Graphical abstract image

      PubDate: 2016-10-15T15:02:36Z
       
  • New dibutyltin(IV) ladders: Syntheses, structures and, optimization and
           evaluation of cytotoxic potential employing A375 (melanoma) and HCT116
           (colon carcinoma) cell lines in vitro
    • Authors: Tushar Basu; Baul Dhrubajyoti Dutta Andrew Duthie Nikhil Guchhait Bruno
      Abstract: Publication date: Available online 15 October 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Tushar S. Basu Baul, Dhrubajyoti Dutta, Andrew Duthie, Nikhil Guchhait, Bruno G.M. Rocha, M. Fátima C. Guedes da Silva, Raveendra B. Mokhamatam, Nune Raviprakash, Sunil K. Manna
      Synthesis and spectroscopic properties of seven new dibutyltin(IV) compounds of 2-{(E)-4-hydroxy-3-[(E)-4-(aryl)iminomethyl]phenyldiazenyl}benzoic acids (LnHH′; n =2–8) with general formula {[Bu2Sn(LnH)]2O}2 (1–7) are reported. The compounds were characterized by elemental analysis and by UV–Visible, fluorescence, IR, 1H, 13C and 119Sn NMR spectroscopies. Solid state structures of dibutyltin(IV) compounds 1–3, 6 and 7 were accomplished from single crystal X-ray crystallography which reveal the common ladder-type structure with two endo- and two exo-Sn atoms. The redox properties of LnHH′ (n =2–4, 7 and 8) and their diorganotin(IV) compounds 1–3, 6 and 7 were also investigated by cyclic voltammetry. In general, the dibutyltin(IV) derivatives exhibited significant in vitro cytotoxic potency towards A375 (melanoma) and HCT116 (colon carcinoma) cell lines as determined by several experiments, like Live and Dead assay, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability assay, LDH (lactate dehydrogenase), cleavage of caspases and PARP (poly(ADP-ribose)polymerase), and DNA fragmentation. Dibutyltin(IV) compounds increase cell death without cytolysis and decreases membrane fluidity, without interfering with p53. Among the dibutyltin(IV) compounds, compound 6 was found to be the most potent, with an IC50 value of 78nM. A mechanism of action for tumor cell death is proposed.
      Graphical abstract image

      PubDate: 2016-10-15T15:02:36Z
       
  • Novel metalloantimalarials: Transmission blocking effects of water soluble
           Cu(I), Ag(I) and Au(I) phosphane complexes on the murine malaria parasite
           Plasmodium berghei
    • Authors: Sofia Tapanelli; Annette Habluetzel; Maura Pellei; Luciano Marchiò; Alessia Tombesi; Ambra Capparè; Carlo Santini
      Abstract: Publication date: Available online 13 October 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Sofia Tapanelli, Annette Habluetzel, Maura Pellei, Luciano Marchiò, Alessia Tombesi, Ambra Capparè, Carlo Santini
      The water soluble phosphane complexes [M(L)4]PF6 (M=Cu(I), Ag(I)) and [Au(L)4]Cl (L=thp (tris(hydroxymethyl)phosphane) or PTA (1,3,5-triaza-7-phosphaadamantane)) showed notable in vitro activity against Plasmodium early sporogonic stages, the sexual forms of the malaria parasite that are responsible for infection of the mosquito vector. Effects varied according to both, the type of metal and phosphane ligands. [Ag(thp)4]PF6 was the best performing complex exhibiting a half inhibitory concentration (IC50) value in the low micromolar range (0.3–15.6μM). The silver complex [Ag(thp)4]PF6 was characterized by X-ray crystallography revealing that the structure comprises the cationic complex [Ag(thp)4]+, the PF6 − anion, and a water molecule of crystallization. Our results revealed that Cu(I), Ag(I) and Au(I) phosphanes complexes elicited similar activity profiles showing potential for the development of antimalarial, transmission blocking compounds. Molecules targeting the sexual parasite stages in the human and/or mosquito host are urgently needed to complement current artemisinin based treatments and next generation antimalarials in a vision not only to cure the disease but to interrupt its transmission.
      Graphical abstract image

      PubDate: 2016-10-15T15:02:36Z
      DOI: 10.1016/j.jinorgbio.2016.10.004
       
  • Rat liver mitochondrial dysfunction by addition of copper(II) or iron(III)
           ions
    • Authors: Christian Rosario; Musacco-Sebio Juan Acosta Bajicoff Paola Paredes-Fleitas Alberto Boveris
      Abstract: Publication date: Available online 14 October 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Christian Saporito-Magriñá, Rosario Musacco-Sebio, Juan M. Acosta, Sofía Bajicoff, Paola Paredes-Fleitas, Alberto Boveris, Marisa G. Repetto
      Increased copper (Cu) and iron (Fe) levels in liver and brain are associated to oxidative stress and damage with increased phospholipid oxidation process. The aim of this work was to assess the toxic effects of Cu2+ and Fe3+ addition to rat liver mitochondria by determining mitochondrial respiration in states 3 (active respiration) and 4 (resting respiration), and phospholipid peroxidation. Both, Cu2+ and Fe3+ produced decreases in O2 consumption in a concentration-dependent manner in active state 3: both ions by 42% with malate-glutamate as complex I substrate (concentration for half maximal response (C50) 60μM Cu2+ and 1.25mM Fe3+), and with succinate as complex II substrate: 64–69% with C50 of 50μM Cu2+ and with C50 of 1.25mM of Fe3+. Respiratory control decreased with Cu2+ (C50 50μM) and Fe3+ (C50 1.25-1-75mM) with both substrates. Cu2+ produced a 2-fold increase and Fe3+ a 5-fold increase of thiobarbituric acid-reactive substances (TBARS) content from 25μM Cu2+ (C50 40μM) and from 100μM Fe3+ (C50 1.75mM). Supplementations with Cu2+ and Fe3+ ions induce mitochondrial dysfunction with phospholipid peroxidation in rat liver mitochondria. Although is proved that a Fenton/Haber Weiss mechanism of oxidative damage occurs in metal-ion induced mitochondrial toxicity, slightly different responses to the metal ions suggest some differences in the mechanism of intracellular toxicity. The decreased rates of mitochondrial respiration and the alteration of mitochondrial function by phospholipid and protein oxidations lead to mitochondrial dysfunction, cellular dyshomeostasis and cell death.
      Graphical abstract image

      PubDate: 2016-10-15T15:02:36Z
       
 
 
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