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  Subjects -> CHEMISTRY (Total: 849 journals)
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    - PHYSICAL CHEMISTRY (65 journals)

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: 8)
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: 8)
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: 20)
Inorganic Chemistry Communications     Hybrid Journal   (Followers: 9)
Inorganic Chemistry Frontiers     Full-text available via subscription   (Followers: 2)
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: 5)
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]   [5 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0162-0134
   Published by Elsevier Homepage  [3038 journals]
  • 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)
       
  • Antiproliferative properties and biomolecular interactions of three Pd(II)
           and Pt(II) complexes
    • Authors: Lara Massai; Alessandro Pratesi; Jovana Bogojeski; Marco Banchini; Serena Pillozzi; Luigi Messori; Živadin D. Bugarčić
      Pages: 1 - 6
      Abstract: Publication date: Available online 30 September 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Lara Massai, Alessandro Pratesi, Jovana Bogojeski, Marco Banchini, Serena Pillozzi, Luigi Messori, Živadin D. Bugarčić
      Three Pd(II) and Pt(II) complexes with chelating mono(imidazolin-2-imine) and bis(imidazolin-2-imine) ligands i.e. [Pd(DMEAImiPr)Cl2] (1) (DMEAImiPr, 2-(1,3-diisopropyl-4,5-dimethylimidazolin-2-imine)ethan-1-dimethylamine), [Pd(DACH(ImiPr) 2)Cl2] (2) (DACH(ImiPr) 2, N,N′-(cyclohexane-1,2-diyl)bis(1,3-diisopropyl-4,5-dimethylimidazolin-2-imine)) and [Pt(DMEAImiPr)Cl2] (3), are evaluated here as potential cytotoxic and anticancer agents. An acceptable solution behaviour was found for the three study compounds in terms of solubility and stability. Notably, the three metal complexes demonstrated moderate to high cytotoxic properties in selected cancer cell lines (liquid and solid tumor). To gain deeper mechanistic insight, the reactivity of the study complexes with model DNA oligos and protein molecules was investigated through spectrometric and spectroscopic methods; in both cases adduct formation was clearly documented by ESI-MS measurements. The binding of these metal complexes to calf thymus DNA (CT-DNA) was further examined by absorption (UV–Vis) and emission spectral studies (Ethidium bromide displacement studies, EtBr). Overall, the studied complexes 1–3 exhibited a remarkable DNA binding ability that might be linked to the observed cytotoxic effects. Interestingly our results revealed that DNA binding, as well as anticancer activity of 1–3 follows the order 2 > 3 > 1. The implications of these findings are discussed.
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      PubDate: 2016-10-01T15:00:54Z
      DOI: 10.1016/j.jinorgbio.2016.09.016
      Issue No: Vol. 165 (2016)
       
  • Biochemical characterization and zinc binding group (ZBGs) inhibition
           studies on the catalytic domain of MMP7 (cdMMP7)
    • Authors: Fan Meng; Hao Yang; Colin Jack; Huaqun Zhang; Abraham Moller; Devin Spivey; Richard C. Page; David L. Tierney; Michael W. Crowder
      Pages: 7 - 17
      Abstract: Publication date: Available online 14 October 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Fan Meng, Hao Yang, Colin Jack, Huaqun Zhang, Abraham Moller, Devin Spivey, Richard C. Page, David L. Tierney, Michael W. Crowder
      Matrix metalloproteinase 7 (MMP7/matrilysin-1) has been implicated in many pathological conditions, such as in cancer and inflammatory diseases; therefore, MMP7 has been targeted for drugs. Success in developing a clinical inhibitor, which exhibits suitable specificity and selectivity, will likely require structural and/or kinetic evaluation of enzyme/inhibitor interactions. To enable these future studies we herein describe the over-expression, purification, and characterization of the catalytic domain of MMP7 (cdMMP7). cdMMP7 was over-expressed in an E. coli over-expression system, and the resulting enzyme was processed into inclusion bodies, which were subsequently solubilized, enabling the enzyme to be re-folded into a catalytically-active form. cdMMP7 was shown to bind 1.8eq of Zn(II), exhibit steady-state kinetic constants of 0.4s−1 for k cat and 23μM for Km, and yield CD and fluorescence spectra that are consistent with a properly-folded enzyme. Pre-steady state kinetic studies yielded kinetic mechanisms of cdMMP7, and these mechanisms are similar to those of other MMPs. Inhibition studies on cdMMP7 with four zinc binding group (ZBG) inhibitors showed that maltol, thiomaltol, and allothiomaltol are better inhibitors with lower IC50 values and lower Kd values against cdMMP7 and cdMMP16 than the commonly-used ZBG inhibitor acetohydroxamic acid. Docking studies suggest that improved inhibitory character may be due to interactions with the S1′ substrate binding pocket. Finally, a ZnCo-heterobimetallic analog of cdMMP7 with Co(II) bound in the catalytic site was prepared and characterized. This study describes a well-characterized analog of MMP7 that is available for future inhibitor design efforts.
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      PubDate: 2016-10-15T15:02:36Z
      DOI: 10.1016/j.jinorgbio.2016.10.005
      Issue No: Vol. 165 (2016)
       
  • Synthesis, crystal structures, DFT studies, molecular docking and urease
           inhibition studies of three Ni(II) complexes with a sexidentate N2O4-donor
           bis-Schiff base ligand
    • Authors: Hu Wang; Tianxiang Lan; Xia Zhang; Dongmei Zhang; Caifeng Bi; Yuhua Fan
      Pages: 18 - 24
      Abstract: Publication date: Available online 14 October 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Hu Wang, Tianxiang Lan, Xia Zhang, Dongmei Zhang, Caifeng Bi, Yuhua Fan
      Three Ni(II) complexes with a sexidentate N2O4-donor bis-Schiff base ligand, namely Ni(C36H34N2O8)·2CH3OH (1), Ni(C28H34N2O8S2)·H2O (2) and Ni(C40H36N4O8)·3CH3OH (3) (C36H34N2O8 =1,2-bis(2-methoxy-6-formylphenoxy)ethane-L-phenylalanine; C28H34N2O8S2 =1,2-bis(2-methoxy-6-formylphenoxy)ethane-L-methionine; C40H36N4O8 =1,2-bis(2-methoxy-6-formylphenoxy)ethane-L-tryptophan) were synthesized and structurally characterized. Theoretical studies of the three complexes were carried out by density functional theory (DFT) Becke's three-parameter hybrid (B3LYP) method employing the 6-31G basis set. Moreover, the inhibitory activities were tested in vitro against jack bean urease. At the same time, molecular docking was investigated to determine the probable binding mode by inserting the complexes into the active site of jack bean urease. The experimental values and docking simulation exhibited that complex 3 showed strong inhibitory activity (IC50 =11.27±2.08μM) compared with the positive reference acetohydroxamic acid. Their structure-activity relationships were further discussed.
      Graphical abstract image

      PubDate: 2016-10-15T15:02:36Z
      DOI: 10.1016/j.jinorgbio.2016.10.006
      Issue No: Vol. 165 (2016)
       
  • Organometallic myoglobins: Formation of Fe–carbon bonds and distal
           pocket effects on aryl ligand conformations
    • Authors: Bing Wang; Leonard M. Thomas; George B. Richter-Addo
      Pages: 1 - 4
      Abstract: Publication date: November 2016
      Source:Journal of Inorganic Biochemistry, Volume 164
      Author(s): Bing Wang, Leonard M. Thomas, George B. Richter-Addo
      Bioorganometallic Fe–C bonds are biologically relevant species that may result from the metabolism of natural or synthetic hydrazines. The molecular structures of four new sperm whale mutant myoglobin derivatives with Fe–aryl moieties, namely H64A–tolyl-m, H64A–chlorophenyl-p, H64Q–tolyl-m, and H64Q–chlorophenyl-p, have been determined at 1.7–1.9Å resolution. The structures reveal conformational preferences for the substituted aryls resulting from attachment of the aryl ligands to Fe at the site of net –NHNH2 release from the precursor hydrazines, and show distal pocket changes that readily accommodate these bulky ligands.
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      PubDate: 2016-11-04T01:16:53Z
      DOI: 10.1016/j.jinorgbio.2016.06.028
      Issue No: Vol. 164 (2016)
       
  • Insights into the anti-angiogenic properties of phosphaplatins
    • Authors: Lu Yang; Shadi Moghaddas; Homa Dezvareh; Louiza Belkacemi; Steven J. Bark; Rathindra N. Bose; Loi H. Do
      Pages: 5 - 16
      Abstract: Publication date: November 2016
      Source:Journal of Inorganic Biochemistry, Volume 164
      Author(s): Lu Yang, Shadi Moghaddas, Homa Dezvareh, Louiza Belkacemi, Steven J. Bark, Rathindra N. Bose, Loi H. Do
      Phosphaplatins are platinum-based antitumor compounds that, unlike other clinically utilized platinum drugs (i.e. cisplatin, carboplatin, and oxaliplatin), appear to target proteins rather than DNA. Because of their unique mode of action, phosphaplatins are promising drug candidates for cisplatin-resistant cancers. In this study, we discovered that Pt(II) and Pt(IV) phosphaplatins possess diverse antitumor properties. In addition to targeting apoptosis antigen (FAS) and proapoptotic gene products as described previously, phosphaplatins also target angiogenesis. We demonstrate that phosphaplatins inhibit human umbilical vein endothelial cell (HUVEC) migration and tube formation in vitro and suppress tumor angiogenesis and growth in immunodeficient mice that were inoculated with A2780 ovarian cancer cells in vivo. To provide insight into this novel antitumor mechanism, phosphaplatin-treated HUVECs were found to exhibit lower gene expression levels of vascular endothelial growth factors (VEGFs) and the VEGFR-2 receptor compared to untreated cells. Kinase inhibition studies suggest that phosphaplatins are inhibitors of VEGFR-2. In ligand exchange experiments using both Pt atomic absorption and 31P NMR spectroscopies, we show that phosphaplatins most likely bind to VEGFR-2 through metal-ligand coordination rather than electrostatic interactions. These studies enhance our understanding of the diverse and novel mechanisms of action of the phosphaplatin antitumor agents, which could potentially be used as chemotherapeutic agents against cisplatin-resistant cancers.
      Graphical abstract image

      PubDate: 2016-11-04T01:16:53Z
      DOI: 10.1016/j.jinorgbio.2016.07.020
      Issue No: Vol. 164 (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
      Abstract: Publication date: Available online 24 November 2016
      Source:Journal of Inorganic Biochemistry
      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).
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      PubDate: 2016-11-29T18:33:42Z
      DOI: 10.1016/j.jinorgbio.2016.11.028
       
  • 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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
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      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
       
  • Ru(III) anticancer agents with aromatic and non-aromatic dithiocarbamates
           as ligands: Loading into nanocarriers and preliminary biological studies
    • Authors: S. Scintilla; L. Brustolin; A. Gambalunga; F. Chiara; A. Trevisan; C. Nardon; D. Fregona
      Abstract: Publication date: Available online 16 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): S. Scintilla, L. Brustolin, A. Gambalunga, F. Chiara, A. Trevisan, C. Nardon, D. Fregona
      Since the discovery of cisplatin in the 1960s, other metal complexes have been investigated as potential antitumor agents to overcome the side-effects associated with the administration of the Pt-based drug. In line with our previous research, in this work we report the synthesis and characterization of mono- and dinuclear Ru(III) complexes with the pyrrolidinedithiocarbamate (PDT) ligand and the more sterically-hindered carbazole-dithiocarbamato ligand (CDT), to compare their properties (both at the chemical and antiproliferative level), in an attempt to assess a structure-activity rationale. Moreover, to overcome the scarce solubility under physiological conditions of the Ru(III)-dithiocarbamato compounds, the biocompatible copolymer Pluronic® F127 has been used, to encapsulate the metal derivatives in water-soluble micellar carriers. Finally, preliminary biological evaluations on CDT and PDT compounds along with their nanoformulations, open intriguing perspectives in anticancer chemotherapy. In particular, comparing the structure of the Ru(III) derivatives, the ionic dinuclear PDT complex shows an important cytotoxic action in comparison to its neutral counterparts. Moreover, the micellar carrier improves the overall activity of the encapsulated Ru(III)-PDT chemotherapeutics. On the other hand, the nanoformulation of the CDT derivatives allows us to solubilize both the 1:3 and the 2:5 complexes and to state their inactivity.
      Graphical abstract image

      PubDate: 2016-11-17T18:00:02Z
      DOI: 10.1016/j.jinorgbio.2016.11.018
       
  • 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
       
  • The anticancer effect related to disturbances in redox balance on Caco-2
           cells caused by an alkynyl gold(I) complex
    • Authors: Cristina Sánchez-de-Diego; Inés Mármol; Rocío Pérez; Sonia Gascón; Mª Jesús Rodriguez-Yoldi; Elena Cerrada
      Abstract: Publication date: Available online 4 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Cristina Sánchez-de-Diego, Inés Mármol, Rocío Pérez, Sonia Gascón, Mª Jesús Rodriguez-Yoldi, Elena Cerrada
      The alkynyl gold(I) derivative [Au(C≡CPh)(PTA)] (PTA = 1,3,5-triaza-7-phosphaadamantane) induces apoptosis in colorectal carcinoma tumour cells (Caco-2) without affecting to normal enterocytes. [Au(C≡CPh)(PTA)] is a slight lipophilic drug, stable in PBS (Phosphate Buffered Saline) and able to bind BSA (Bovin Serum Albumin) by hydrophobic interactions. Once inside the cell, [Au(C≡CPh)(PTA)] targets seleno proteins such as Thioredoxin Reductase 1, increasing ROS (Reactive Oxygen Species) levels, reducing cell viability and proliferation and inducing mitochondrial apoptotic pathway, pro-apoptotic and anti-apoptotic protein imbalance, loss of mitochondrial membrane potential, cytochrome c release and activation of caspase 9 and 3. Moreover, unlike other metal-based drugs such as cisplatin, [Au(C≡CPh)(PTA)] does not target nucleic acid, reducing the risk of side mutation in the DNA. In consequence, our results predict a promising future for [Au(C≡CPh)(PTA)] as a chemotherapeutic agent for colorectal carcinoma.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.009
       
  • The anticancer effect related to disturbances in redox balance on Caco-2
           cells caused by an alkynyl gold(I) complex
    • Authors: Cristina Sánchez-de-Diego; Inés Mármol; Rocío Pérez; Sonia Gascón; Mª Jesús Rodriguez-Yoldi; Elena Cerrada
      Abstract: Publication date: Available online 4 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Cristina Sánchez-de-Diego, Inés Mármol, Rocío Pérez, Sonia Gascón, Mª Jesús Rodriguez-Yoldi, Elena Cerrada
      The alkynyl gold(I) derivative [Au(C≡CPh)(PTA)] (PTA = 1,3,5-triaza-7-phosphaadamantane) induces apoptosis in colorectal carcinoma tumour cells (Caco-2) without affecting to normal enterocytes. [Au(C≡CPh)(PTA)] is a slight lipophilic drug, stable in PBS (Phosphate Buffered Saline) and able to bind BSA (Bovin Serum Albumin) by hydrophobic interactions. Once inside the cell, [Au(C≡CPh)(PTA)] targets seleno proteins such as Thioredoxin Reductase 1, increasing ROS (Reactive Oxygen Species) levels, reducing cell viability and proliferation and inducing mitochondrial apoptotic pathway, pro-apoptotic and anti-apoptotic protein imbalance, loss of mitochondrial membrane potential, cytochrome c release and activation of caspase 9 and 3. Moreover, unlike other metal-based drugs such as cisplatin, [Au(C≡CPh)(PTA)] does not target nucleic acid, reducing the risk of side mutation in the DNA. In consequence, our results predict a promising future for [Au(C≡CPh)(PTA)] as a chemotherapeutic agent for colorectal carcinoma.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.009
       
  • G2/M cell cycle arrest on HT-29 cancer cells and toxicity assessment of
           triphenylphosphanegold(I) carbonimidothioates, Ph3PAu[SC(OR)=NPh], R=Me,
           Et, and iPr, during zebrafish development
    • Authors: Kah Kooi Ooi; Chien Ing Yeo; Theventhiran Mahandaran; Kok Pian Ang; Abdah Md Akim; Yoke-Kqueen Cheah; Hoi-Ling Seng; Edward R.T. Tiekink
      Abstract: Publication date: Available online 4 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Kah Kooi Ooi, Chien Ing Yeo, Theventhiran Mahandaran, Kok Pian Ang, Abdah Md Akim, Yoke-Kqueen Cheah, Hoi-Ling Seng, Edward R.T. Tiekink
      Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), were previously shown to be significantly cytotoxic toward HT-29 cancer cells and to induce cell death by both intrinsic and extrinsic apoptotic pathways whereby 1 activated the p73 gene, and each of 2 and 3 activated p53; 2 also caused apoptotic cell death via the c-Jun. N-terminal kinase/mitogen-activated protein kinase pathway. Apoptosis pathways have been further evaluated by mitochondrial cytochrome c measurements and annexin V screening, confirming apoptotic pathways of cell death. Cell cycle analysis showed the majority of treated HT-29 cells were arrested at the G2/M checkpoint after 24h; results of both assays were confirmed by changes in populations of relevant genes (PCR array analysis). Cell invasion studies showed inhibition of metastasis through Matrigel™ matrix to 17–22% cf. untreated cells. LC50 values were determined in zebrafish (8.36, 8.17, and 7.64μM for 1–3). Finally, the zebrafish tolerated doses of 1 and 2 up to 0.625μM, and 3 was tolerated at even higher doses of up to 1.25μM.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.008
       
  • G2/M cell cycle arrest on HT-29 cancer cells and toxicity assessment of
           triphenylphosphanegold(I) carbonimidothioates, Ph3PAu[SC(OR)=NPh], R=Me,
           Et, and iPr, during zebrafish development
    • Authors: Kah Kooi Ooi; Chien Ing Yeo; Theventhiran Mahandaran; Kok Pian Ang; Abdah Md Akim; Yoke-Kqueen Cheah; Hoi-Ling Seng; Edward R.T. Tiekink
      Abstract: Publication date: Available online 4 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Kah Kooi Ooi, Chien Ing Yeo, Theventhiran Mahandaran, Kok Pian Ang, Abdah Md Akim, Yoke-Kqueen Cheah, Hoi-Ling Seng, Edward R.T. Tiekink
      Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), were previously shown to be significantly cytotoxic toward HT-29 cancer cells and to induce cell death by both intrinsic and extrinsic apoptotic pathways whereby 1 activated the p73 gene, and each of 2 and 3 activated p53; 2 also caused apoptotic cell death via the c-Jun. N-terminal kinase/mitogen-activated protein kinase pathway. Apoptosis pathways have been further evaluated by mitochondrial cytochrome c measurements and annexin V screening, confirming apoptotic pathways of cell death. Cell cycle analysis showed the majority of treated HT-29 cells were arrested at the G2/M checkpoint after 24h; results of both assays were confirmed by changes in populations of relevant genes (PCR array analysis). Cell invasion studies showed inhibition of metastasis through Matrigel™ matrix to 17–22% cf. untreated cells. LC50 values were determined in zebrafish (8.36, 8.17, and 7.64μM for 1–3). Finally, the zebrafish tolerated doses of 1 and 2 up to 0.625μM, and 3 was tolerated at even higher doses of up to 1.25μM.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.008
       
  • 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
       
  • Antioxidant and anticancer effects and bioavailability studies of the
           flavonoid baicalin and its oxidovanadium(IV) complex
    • Authors: Juan J. Martinez Medina; Luciana G. Naso; Ana L. Pérez; Alberto Rizzi; Evelina G. Ferrer; Patricia A.M. Williams
      Abstract: Publication date: Available online 5 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Juan J. Martinez Medina, Luciana G. Naso, Ana L. Pérez, Alberto Rizzi, Evelina G. Ferrer, Patricia A.M. Williams
      Based on the known antioxidant effect of flavonoids, baicalin (baic) found in roots of Scutellaria has been selected. Its coordination complex with the oxidovanadium(IV) cation, Na4[VO(baic)2].6H2O (VIVO(baic)), was synthesized at pH9 in ethanol and characterized by physicochemical methods. Spectrophotometric studies at pH9 showed a ligand: metal stoichiometry of 2:1. By vibrational spectroscopy a coordination mode through the cis 5-OH and 6-OH deprotonated groups is inferred. EPR spectroscopy shows an environment of four aryloxide (ArO−) groups in the equatorial plane of the V=O moiety, both in solution and in the solid complex. The antioxidant capacity against superoxide and peroxyl radicals of VIVO(baic) resulted greater than for baicalin and correlated with previous results obtained for other VOflavonoid complexes. The coordination mode produces delocalization of the electron density and the stabilization of the radical formed by interaction with external radicals. The complex and the ligand displayed no toxic (Artemia salina test) and no mutagenic (Ames test) effects. The complex improved the ability of the ligand to reduce cell viability of human lung cancer cell lines (A549) generating reactive oxygen species (ROS) in cells, being this effect reversed by pre-incubation of the cells with antioxidants such as vitamins C and E. The addition of NAC (N-acetyl-L-cysteine, a sequestering agent of free radicals) suppresses the anticancer effect, confirming the oxidative stress mechanism. The complex interacted with bovine serum albumin (BSA) with stronger binding than baicalin and the mechanisms involved H bonding and van der Waals interactions.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.005
       
  • Antioxidant and anticancer effects and bioavailability studies of the
           flavonoid baicalin and its oxidovanadium(IV) complex
    • Authors: Juan J. Martinez Medina; Luciana G. Naso; Ana L. Pérez; Alberto Rizzi; Evelina G. Ferrer; Patricia A.M. Williams
      Abstract: Publication date: Available online 5 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Juan J. Martinez Medina, Luciana G. Naso, Ana L. Pérez, Alberto Rizzi, Evelina G. Ferrer, Patricia A.M. Williams
      Based on the known antioxidant effect of flavonoids, baicalin (baic) found in roots of Scutellaria has been selected. Its coordination complex with the oxidovanadium(IV) cation, Na4[VO(baic)2].6H2O (VIVO(baic)), was synthesized at pH9 in ethanol and characterized by physicochemical methods. Spectrophotometric studies at pH9 showed a ligand: metal stoichiometry of 2:1. By vibrational spectroscopy a coordination mode through the cis 5-OH and 6-OH deprotonated groups is inferred. EPR spectroscopy shows an environment of four aryloxide (ArO−) groups in the equatorial plane of the V=O moiety, both in solution and in the solid complex. The antioxidant capacity against superoxide and peroxyl radicals of VIVO(baic) resulted greater than for baicalin and correlated with previous results obtained for other VOflavonoid complexes. The coordination mode produces delocalization of the electron density and the stabilization of the radical formed by interaction with external radicals. The complex and the ligand displayed no toxic (Artemia salina test) and no mutagenic (Ames test) effects. The complex improved the ability of the ligand to reduce cell viability of human lung cancer cell lines (A549) generating reactive oxygen species (ROS) in cells, being this effect reversed by pre-incubation of the cells with antioxidants such as vitamins C and E. The addition of NAC (N-acetyl-L-cysteine, a sequestering agent of free radicals) suppresses the anticancer effect, confirming the oxidative stress mechanism. The complex interacted with bovine serum albumin (BSA) with stronger binding than baicalin and the mechanisms involved H bonding and van der Waals interactions.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.005
       
  • 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
       
  • Targeting human telomeric and c-myc G-quadruplexes with
           alkynylplatinum(II) terpyridine complexes under molecular crowding
           conditions
    • Authors: Zhize Ou; Yunqing Wang; Yunyan Gao; Xiaobing Wang; Yimeng Qian; Yi Li; Xuesong Wang
      Abstract: Publication date: Available online 9 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Zhize Ou, Yunqing Wang, Yunyan Gao, Xiaobing Wang, Yimeng Qian, Yi Li, Xuesong Wang
      The interactions between alkynylplatinum(II) terpyridine complexes 1–3 and the G-quadruplex DNA, including c-myc and telomeric quadruplex DNA, are investigated both in dilute solution and under molecular crowding conditions. The UV–vis absorption spectroscopy, circular dichroism and molecular docking studies suggest that 1–3 associate with telomeric and c-myc G-quadruplexes via groove binding, and electrostatic interactions. Experimental studies indicate that under molecular crowding conditions (in the presence of 40wt% PEG 200), 1–2 show weak affinity for c-myc, while 3 still displays high affinity and selectivity for c-myc. On the other hand, 1–3 act as efficient and selective ligand for telomeric quadruplex DNA under molecular crowding conditions. The complex 3 exhibits excellent cytotoxicity against A549, K562 and SGC-7901, with IC50 values that are 35.0-fold, 10.0-fold, and 12.1-fold lower than the values of cisplatin under the same conditions, respectively.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.012
       
  • Mammalian agmatinases constitute unusual members in the family of
           Mn2+-dependent ureahydrolases
    • Authors: Nicol Romero; José Benítez; David Garcia; Arlette González; Leonardo Bennun; María A. García-Robles; Vasthi López; Liam A. Wilson; Gerhard Schenk; Nelson Carvajal; Elena Uribe
      Abstract: Publication date: Available online 9 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Nicol Romero, José Benítez, David Garcia, Arlette González, Leonardo Bennun, María A. García-Robles, Vasthi López, Liam A. Wilson, Gerhard Schenk, Nelson Carvajal, Elena Uribe
      Agmatine (1-amino-4-guanidinobutane) plays an important role in a range of metabolic functions, in particular in the brain. Agmatinases (AGMs) are enzymes capable of converting agmatine to the polyamine putrescine and urea. AGMs belong to the family of Mn2+-dependent ureahydrolases. However, no AGM from a mammalian source has yet been extracted in catalytically active form. While in human AGM the six amino acid ligands that coordinate the two Mn2+ ions in the active site are conserved, four mutations are observed in the murine enzyme. Here, we demonstrate that similar to its human counterpart murine AGM does not appear to have in vitro catalytic activity, independent of the presence of Mn2+. However, in presence of agmatine both enzymes are very efficient in promoting cell growth of a yeast strain that is deficient in polyamine biosynthesis (Saccharomyces cerevisiae strain TRY104Δspe1). Furthermore, mutations among the putative Mn2+ binding residues had no effect on the ability of murine AGM to promote growth of the yeast culture. It thus appears that mammalian AGMs form a distinct group within the family of ureahydrolases that (i) either fold in a manner distinct from other members in this family, or (ii) require accessory proteins to bind Mn2+ in a mechanism related to that observed for the Ni2+-dependent urease.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.015
       
  • Mammalian agmatinases constitute unusual members in the family of
           Mn2+-dependent ureahydrolases
    • Authors: Nicol Romero; José Benítez; David Garcia; Arlette González; Leonardo Bennun; María A. García-Robles; Vasthi López; Liam A. Wilson; Gerhard Schenk; Nelson Carvajal; Elena Uribe
      Abstract: Publication date: Available online 9 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Nicol Romero, José Benítez, David Garcia, Arlette González, Leonardo Bennun, María A. García-Robles, Vasthi López, Liam A. Wilson, Gerhard Schenk, Nelson Carvajal, Elena Uribe
      Agmatine (1-amino-4-guanidinobutane) plays an important role in a range of metabolic functions, in particular in the brain. Agmatinases (AGMs) are enzymes capable of converting agmatine to the polyamine putrescine and urea. AGMs belong to the family of Mn2+-dependent ureahydrolases. However, no AGM from a mammalian source has yet been extracted in catalytically active form. While in human AGM the six amino acid ligands that coordinate the two Mn2+ ions in the active site are conserved, four mutations are observed in the murine enzyme. Here, we demonstrate that similar to its human counterpart murine AGM does not appear to have in vitro catalytic activity, independent of the presence of Mn2+. However, in presence of agmatine both enzymes are very efficient in promoting cell growth of a yeast strain that is deficient in polyamine biosynthesis (Saccharomyces cerevisiae strain TRY104Δspe1). Furthermore, mutations among the putative Mn2+ binding residues had no effect on the ability of murine AGM to promote growth of the yeast culture. It thus appears that mammalian AGMs form a distinct group within the family of ureahydrolases that (i) either fold in a manner distinct from other members in this family, or (ii) require accessory proteins to bind Mn2+ in a mechanism related to that observed for the Ni2+-dependent urease.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.015
       
  • Evaluation of cellular uptake, cytotoxicity and cellular ultrastructural
           effects of heteroleptic oxidovanadium(IV) complexes of salicylaldimines
           and polypyridyl ligands
    • Authors: Gonzalo Scalese; Isabel Correia; Julio Benítez; Santiago Rostán; Fernanda Marques; Filipa Mendes; António Pedro Matos; João Costa Pessoa; Dinorah Gambino
      Abstract: Publication date: Available online 9 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Gonzalo Scalese, Isabel Correia, Julio Benítez, Santiago Rostán, Fernanda Marques, Filipa Mendes, António Pedro Matos, João Costa Pessoa, Dinorah Gambino
      Searching for prospective vanadium-based drugs for cancer treatment, a new series of structurally related [VIVO(L-2H)(NN)] compounds (1–8) was developed. They include a double deprotonated salicylaldimine Schiff base ligand (L-2H) and different NN-polypyridyl co-ligands having DNA intercalating capacity. Compounds were characterized in solid state and in solution. EPR spectroscopy suggests that the NN ligands act as bidentate and bind through both nitrogen donor atoms in an axial-equatorial mode. The cytotoxicity was evaluated in human tumoral cells (ovarian A2780, breast MCF7, prostate PC3). The cytotoxic activity was dependent on type of cell and incubation time. At 24h PC3 cells presented low sensitivity, but at 72h all complexes showed high cytotoxic activity in all cells. Human kidney HEK293 and ovarian cisplatin resistant A2780cisR cells were also included to evaluate selectivity towards cancer cells and potency to overcome cisplatin resistance, respectively. Most complexes showed no detectable interaction with plasmid DNA, except 2 and 7 which depicted low ability to induce single strand breaks in supercoiled DNA. Based on the overall cytotoxic profile, complexes with 2,2´-bipyridine and 1,10-phenanthroline ligands (1 and 2) were selected for further studies, which consisted on cellular distribution and ultrastructural analyses. In the A2780 cells both depicted different distribution profiles; the former accumulates mostly at the membrane and the latter in the cytoskeleton. Morphology of treated cells showed nuclear atypia and membrane alterations, more severe for 1. Complexes induce different cell death pathways, predominantly necrosis for 1 and apoptosis for 2. Complexes alternative mode of cell death motivates the possibility for further developments.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.010
       
  • Evaluation of cellular uptake, cytotoxicity and cellular ultrastructural
           effects of heteroleptic oxidovanadium(IV) complexes of salicylaldimines
           and polypyridyl ligands
    • Authors: Gonzalo Scalese; Isabel Correia; Julio Benítez; Santiago Rostán; Fernanda Marques; Filipa Mendes; António Pedro Matos; João Costa Pessoa; Dinorah Gambino
      Abstract: Publication date: Available online 9 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Gonzalo Scalese, Isabel Correia, Julio Benítez, Santiago Rostán, Fernanda Marques, Filipa Mendes, António Pedro Matos, João Costa Pessoa, Dinorah Gambino
      Searching for prospective vanadium-based drugs for cancer treatment, a new series of structurally related [VIVO(L-2H)(NN)] compounds (1–8) was developed. They include a double deprotonated salicylaldimine Schiff base ligand (L-2H) and different NN-polypyridyl co-ligands having DNA intercalating capacity. Compounds were characterized in solid state and in solution. EPR spectroscopy suggests that the NN ligands act as bidentate and bind through both nitrogen donor atoms in an axial-equatorial mode. The cytotoxicity was evaluated in human tumoral cells (ovarian A2780, breast MCF7, prostate PC3). The cytotoxic activity was dependent on type of cell and incubation time. At 24h PC3 cells presented low sensitivity, but at 72h all complexes showed high cytotoxic activity in all cells. Human kidney HEK293 and ovarian cisplatin resistant A2780cisR cells were also included to evaluate selectivity towards cancer cells and potency to overcome cisplatin resistance, respectively. Most complexes showed no detectable interaction with plasmid DNA, except 2 and 7 which depicted low ability to induce single strand breaks in supercoiled DNA. Based on the overall cytotoxic profile, complexes with 2,2´-bipyridine and 1,10-phenanthroline ligands (1 and 2) were selected for further studies, which consisted on cellular distribution and ultrastructural analyses. In the A2780 cells both depicted different distribution profiles; the former accumulates mostly at the membrane and the latter in the cytoskeleton. Morphology of treated cells showed nuclear atypia and membrane alterations, more severe for 1. Complexes induce different cell death pathways, predominantly necrosis for 1 and apoptosis for 2. Complexes alternative mode of cell death motivates the possibility for further developments.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.010
       
  • 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
       
  • Targeting human telomeric and c-myc G-quadruplexes with
           alkynylplatinum(II) terpyridine complexes under molecular crowding
           conditions
    • Authors: Zhize Ou; Yunqing Wang; Yunyan Gao; Xiaobing Wang; Yimeng Qian; Yi Li; Xuesong Wang
      Abstract: Publication date: Available online 9 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Zhize Ou, Yunqing Wang, Yunyan Gao, Xiaobing Wang, Yimeng Qian, Yi Li, Xuesong Wang
      The interactions between alkynylplatinum(II) terpyridine complexes 1–3 and the G-quadruplex DNA, including c-myc and telomeric quadruplex DNA, are investigated both in dilute solution and under molecular crowding conditions. The UV–vis absorption spectroscopy, circular dichroism and molecular docking studies suggest that 1–3 associate with telomeric and c-myc G-quadruplexes via groove binding, and electrostatic interactions. Experimental studies indicate that under molecular crowding conditions (in the presence of 40wt% PEG 200), 1–2 show weak affinity for c-myc, while 3 still displays high affinity and selectivity for c-myc. On the other hand, 1–3 act as efficient and selective ligand for telomeric quadruplex DNA under molecular crowding conditions. The complex 3 exhibits excellent cytotoxicity against A549, K562 and SGC-7901, with IC50 values that are 35.0-fold, 10.0-fold, and 12.1-fold lower than the values of cisplatin under the same conditions, respectively.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.012
       
  • Inactivation of urease by catechol: Kinetics and structure
    • Authors: Luca Mazzei; Michele Cianci; Francesco Musiani; Gábor Lente; Marta Palombo; Stefano Ciurli
      Abstract: Publication date: Available online 9 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Luca Mazzei, Michele Cianci, Francesco Musiani, Gábor Lente, Marta Palombo, Stefano Ciurli
      Urease is a Ni(II)-containing enzyme that catalyzes the hydrolysis of urea to yield ammonia and carbamate at a rate 1015 times higher than the uncatalyzed reaction. Urease is a virulence factor of several human pathogens, in addition to decreasing the efficiency of soil organic nitrogen fertilization. Therefore, efficient urease inhibitors are actively sought. In this study, we describe a molecular characterization of the interaction between urease from Sporosarcina pasteurii (SPU) and Canavalia ensiformis (jack bean, JBU) with catechol, a model polyphenol. In particular, catechol irreversibly inactivates both SPU and JBU with a complex radical-based autocatalytic multistep mechanism. The crystal structure of the SPU-catechol complex, determined at 1.50Å resolution, reveals the structural details of the enzyme inhibition.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.016
       
  • 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
       
  • Aza-bridged bisphenanthrolinyl Pt(II) complexes: Efficient stabilization
           and topological selectivity on telomeric G-quadruplexes
    • Authors: Lei He; Zhenyu Meng; Yi-qun Xie; Xiang Chen; Tianhu Li; Fangwei Shao
      Abstract: Publication date: Available online 9 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Lei He, Zhenyu Meng, Yi-qun Xie, Xiang Chen, Tianhu Li, Fangwei Shao
      Two platinum complexes with an aza-bridged bis-phenanthroline ligand (bpa) were synthesized. The two phenanthrolines in bpa entered a flat plane prior to binding of nucleic acids, which bestowed on the two Pt complexes a significantly high stabilizing ability on both DNA and RNA G-quadruplexes. Further extending alkyl tail from aromatic coordination core enabled the complexes to distinguish GQ sequence based upon the topological folding structures and enhanced the selectivity of the complex against duplex DNA. This study paved the way to develop Pt complexes as GQ stabilizers for specific folding topology and the applications to disease and/or personalized anticancer medicine/therapy.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.011
       
  • Aza-bridged bisphenanthrolinyl Pt(II) complexes: Efficient stabilization
           and topological selectivity on telomeric G-quadruplexes
    • Authors: Lei He; Zhenyu Meng; Yi-qun Xie; Xiang Chen; Tianhu Li; Fangwei Shao
      Abstract: Publication date: Available online 9 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Lei He, Zhenyu Meng, Yi-qun Xie, Xiang Chen, Tianhu Li, Fangwei Shao
      Two platinum complexes with an aza-bridged bis-phenanthroline ligand (bpa) were synthesized. The two phenanthrolines in bpa entered a flat plane prior to binding of nucleic acids, which bestowed on the two Pt complexes a significantly high stabilizing ability on both DNA and RNA G-quadruplexes. Further extending alkyl tail from aromatic coordination core enabled the complexes to distinguish GQ sequence based upon the topological folding structures and enhanced the selectivity of the complex against duplex DNA. This study paved the way to develop Pt complexes as GQ stabilizers for specific folding topology and the applications to disease and/or personalized anticancer medicine/therapy.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.011
       
  • Inactivation of urease by catechol: Kinetics and structure
    • Authors: Luca Mazzei; Michele Cianci; Francesco Musiani; Gábor Lente; Marta Palombo; Stefano Ciurli
      Abstract: Publication date: Available online 9 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Luca Mazzei, Michele Cianci, Francesco Musiani, Gábor Lente, Marta Palombo, Stefano Ciurli
      Urease is a Ni(II)-containing enzyme that catalyzes the hydrolysis of urea to yield ammonia and carbamate at a rate 1015 times higher than the uncatalyzed reaction. Urease is a virulence factor of several human pathogens, in addition to decreasing the efficiency of soil organic nitrogen fertilization. Therefore, efficient urease inhibitors are actively sought. In this study, we describe a molecular characterization of the interaction between urease from Sporosarcina pasteurii (SPU) and Canavalia ensiformis (jack bean, JBU) with catechol, a model polyphenol. In particular, catechol irreversibly inactivates both SPU and JBU with a complex radical-based autocatalytic multistep mechanism. The crystal structure of the SPU-catechol complex, determined at 1.50Å resolution, reveals the structural details of the enzyme inhibition.
      Graphical abstract image

      PubDate: 2016-11-10T17:42:24Z
      DOI: 10.1016/j.jinorgbio.2016.11.016
       
  • Polycyclic ferrocenyl(dihydro)thiazepine Derivatives: Diastereo-selective
           synthesis, Characterization, Electrochemical Behavior, Theoretical and
           Biological Investigation
    • Authors: Jessica J. Sánchez García; Yanis Toledano-Magaña; Marcos Flores-Alamo; Elena Martínez-Klimova; Rodrigo Galindo-Murillo; Luis F. Hernández-Ayala; Luis Ortiz-Frade; Juan C. García-Ramos; Elena I. Klimova
      Abstract: Publication date: Available online 2 November 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Jessica J. Sánchez García, Yanis Toledano-Magaña, Marcos Flores-Alamo, Elena Martínez-Klimova, Rodrigo Galindo-Murillo, Luis F. Hernández-Ayala, Luis Ortiz-Frade, Juan C. García-Ramos, Elena I. Klimova
      The reaction of E-2-ferrocenylmethylidenetetralones and E,E-2,6-bis-(ferrocenylmethylidene)-cyclohexanone with 2-aminothiophenol proceed with high diastereoselectivity, forming the ~4.5:1 mixture of trans- and cis-isomers of polycyclic ferrocenylthiazepines, respectively. The reactions of E,E-2,5-bis-(ferrocenylmethylidene)cyclopentanone and E,E-3,5-bis-(ferrocenylmethylidene)-1-methyl-4-piperidone with 2-aminothiophenol take place stereo specifically to form the diastereomeric tricyclic thiazepines of cis- and trans-configuration, respectively. The structures of the obtained compounds were established by IR, 1H and 13C NMR spectroscopy and mass-spectrometry. The structures of the trans-tetralino[1,2a]-, trans-5,7-dimethyltetralino[1,2a]-2-ferrocenyl [1,5]benzo-2,3-dihydrothiazepines and cis-5-ferrocenyl-methylidenecyclopentano[1,2a]-2-ferrocenyl- [1,5]benzo-2,3-dihydrothiazepine were confirmed by X-ray diffraction analysis. An electrochemical study reveals that the diferrocenyl derivatives belong to a Class I compounds of the Robin-Day classification. This behavior is explained by the analysis of frontier orbitals as calculated by density functional theory, showing that only one ferrocenyl unit participates in the generation of HOMO and LUMO orbitals. Compounds 4a and 4c showed similar capacity to inhibit the proliferation of HM1: IMSS trophozoite cultures than the first choice drug for human amoebiasis treatment, metronidazole. Morphological changes induced in the trophozoites after drug exposure suggest a redox in balance as the probable mechanism of the parasite death.
      Graphical abstract image

      PubDate: 2016-11-04T01:16:53Z
      DOI: 10.1016/j.jinorgbio.2016.09.002
       
  • 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
       
  • New copper(I) complexes bearing lomefloxacin motif: Spectroscopic
           properties, in vitro cytotoxicity and interactions with DNA and human
           serum albumin
    • Authors: Urszula K. Komarnicka; Radosław Starosta; Agnieszka Kyzioł; Michał Płotek; Małgorzata Puchalska; Małgorzata Jeżowska-Bojczuk
      Abstract: Publication date: Available online 30 September 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Urszula K. Komarnicka, Radosław Starosta, Agnieszka Kyzioł, Michał Płotek, Małgorzata Puchalska, Małgorzata Jeżowska-Bojczuk
      In this paper we present lomefloxacin's (HLm, 2nd generation fluoroquinolone antibiotic agent) organic and inorganic derivatives: aminomethyl(diphenyl)phosphine (PLm), its oxide as well as new copper(I) iodide or copper(I) thiocyanate complexes with PLm and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,2′-biquinoline (bq) as the auxiliary ligands. The synthesized compounds were fully characterised by NMR, UV–Vis and luminescence spectroscopies. Selected structures were analysed by theoretical DFT (density functional theory) methods. High stability of the complexes in aqueous solutions in the presence of atmosferic oxygen was proven. Cytotoxic activity of all compounds was tested towards three cancer cell lines (CT26 - mouse colon carcinoma, A549 - human lung adenocarcinoma, and MCF7 - human breast adenocarcinoma). All complexes are characterised by cytotoxic activity higher than the activity of the parent drug and its organic derivatives as well as cisplatin. Studied derivatives as well as parent drug do not intercalate to DNA, except Cu(I) complexes with bq ligand. All studied complexes caused single-stranded cleavage of the sugar–phosphate backbone of plasmid DNA. The addition of H2O2 caused distinct changes in the plasmid structure and led to single- and/or double-strain plasmid cleavage. Studied compounds interact with human serum albumin without affecting its secondary structure.
      Graphical abstract image

      PubDate: 2016-10-01T15:00:54Z
      DOI: 10.1016/j.jinorgbio.2016.09.015
       
  • Coordination ability and biological activity of a naringenin
           thiosemicarbazone
    • Authors: Katarzyna Brodowska; Isabel Correia Eugenio Garribba Fernanda Marques Klewicka Costa
      Abstract: Publication date: Available online 30 September 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Katarzyna Brodowska, Isabel Correia, Eugenio Garribba, Fernanda Marques, Elżbieta Klewicka, Elżbieta Łodyga-Chruscińska, João Costa Pessoa, Aliaksandr Dzeikala, Longin Chrusciński
      Graphical abstract image

      PubDate: 2016-10-01T15:00:54Z
       
  • Multiconfigurational and DFT analyses of the electromeric formulation and
           UV–vis absorption spectra of the superoxide adduct of ferrous superoxide
           reductase
    • Authors: Amr A.A. Attia; Daniela Cioloboc; Alexandru Lupan; Radu Silaghi-Dumitrescu
      Abstract: Publication date: Available online 30 September 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Amr A.A. Attia, Daniela Cioloboc, Alexandru Lupan, Radu Silaghi-Dumitrescu
      The putative initial adduct of ferrous superoxide reductase (SOR) with superoxide has been alternatively formulated as ferric-peroxo or ferrous-superoxo. The ~600-nm UV–vis absorption band proposed to be assigned to this adduct (either as sole intermediate in the SOR catalytic cycle, or as one of the two intermediates) has recently been interpreted as due to a ligand-to-metal charge transfer, involving thiolate and superoxide in a ferrous complex, contrary to an alternative assignment as a predominantly cysteine thiolate-to-ferric charge transfer in a ferric-peroxo electromer. In an attempt to clarify the electromeric formulation of this adduct, we report a computational study using a multiconfigurational complete active space self-consistent field (MC-CASSCF) wave function approach as well as modelling the UV–vis absorption spectra with time-dependent density functional theory (TD-DFT). The MC-CASSCF calculations disclose a weak interaction between iron and the dioxygenic ligand and a dominant configuration with an essentially ferrous-superoxo character. The computed UV–vis absorption spectra reveal a marked dependence on the choice of density functional – both in terms of location of bands and in terms of orbital contributors. For the main band in the visible region, besides the recently reported thiolate-to-superoxide charge transfer, a more salient, and less functional-dependent, feature is a thiolate-to-ferric iron charge transfer, consistent with a ferric-peroxo electromer. By contrast, the computed UV–vis spectra of a ferric-hydroperoxo SOR model match distinctly better (and with no qualitative dependence on the DFT methodology) the 600-nm band as due to a mainly thiolate-to-ferric character – supporting the assignment of the SOR “600-nm intermediate” as a S =5/2 ferric-hydroperoxo species.
      Graphical abstract image

      PubDate: 2016-10-01T15:00:54Z
      DOI: 10.1016/j.jinorgbio.2016.09.017
       
  • In vitro and in vivo antitumor activity of a novel carbonyl ruthenium
           compound, the
           ct-[RuCl(CO)(dppb)(bipy)]PF­6[dppb=1,4-bis(disphenylphosphine)butane and
           bipy=2,2'-bipyridine]
    • Authors: Andréa P. Carnizello; Marília I.F. Barbosa; Monize Martins; Natália H. Ferreira; Pollyanna F. Oliveira; Geórgia M. Magalhães; Alzir A. Batista; Denise C. Tavares
      Abstract: Publication date: Available online 25 August 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Andréa P. Carnizello, Marília I.F. Barbosa, Monize Martins, Natália H. Ferreira, Pollyanna F. Oliveira, Geórgia M. Magalhães, Alzir A. Batista, Denise C. Tavares
      This study performed in vitro and in vivo biological assays of the ruthenium (II) compound ct-[RuCl(CO)(dppb)(bipy)]PF6 (where, dppb =1.4-bis(diphenylphosphine)butane and bipy =2.2′-bipyridine). The cytotoxic activity of this compound was evaluated against different tumor cell lines (HeLa, human cervical adenocarcinoma; MCF7, human breast adenocarcinoma; MO59J, human glioblastoma; HepG2, hepatocellular carcinoma and B16F10, murine melanoma) and healthy cell line (V79, Chinese hamster lung fibroblasts), by XTT (sodium 2,3′-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-3,4-tetrazolium]-bis(4-methoxy-6-nitro)benzene-sulfonic acid hydrate) method. A syngeneic murine melanoma tumor model (B16F10) was used to evaluate its antitumor activity. Additionally, experiments were performed to assess the interactions with ctDNA (calf thymus DNA) and BSA (bovine serum albumin). The results showed that ct-[RuCl(CO)(dppb)(bipy)]PF6 was cytotoxic against all tumor cell lines tested. Furthermore, the compound was more effective against tumor cells compared to the normal cell line, indicating selectivity, especially in B16F10 cells. Significant tumor growth reduction was observed in animals treated with the compound compared to the untreated control. Histopathological analysis of tumor tissue revealed a significant reduction of mitosis in animals treated with the compound compared to the untreated control. In the ctDNA and BSA interaction experiments, the compound in study showed weak interactions with ctDNA and hydrophobic interactions with BSA. The ruthenium compound investigated showed promising results in in vitro and in vivo biological assays.
      Graphical abstract image

      PubDate: 2016-08-26T11:07:05Z
      DOI: 10.1016/j.jinorgbio.2016.08.010
       
  • In Situ Synthesis of High Swell Ratio Polyacrylic Acid/Silver
           Nanocomposite Hydrogels and Their Antimicrobial Properties
    • Authors: Yi-Syuan Wei; Ko-Shao Chen; Lii-Tzu Wu
      Abstract: Publication date: Available online 24 August 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Yi-Syuan Wei, Ko-Shao Chen, Lii-Tzu Wu
      Silver nanocomposites embedded within a polymer matrix have attracted attention in recent years. Ionic polymer hydrogels comprise networks of chemically or physically cross-linked polymers that swell considerably in an appropriate solvent. In this study, we used a solution of the carboxylic monomer acrylic acid and silver nitrate to prepare nanocomposite hydrogels through ultraviolet (UV)-light irradiation. Silver-impregnated biomaterial composed of acrylic acid contains only a monomer and no cross-linker. The formation of hydrogels and reduction of silver nanoparticles were affected by the preparation parameters, that is, the monomer concentration and silver nitrate concentration. The morphology, structure, and size of the silver nanocomposite hydrogels were evaluated through field emission scanning electron microscopy and UV–visible absorption. The antimicrobial activity of the samples was tested against fourstandard strains Candida albicans, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli; and five clinical bacterial isolates Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumonia. The silver nanocomposite hydrogels exhibited an interconnected porous structure and could absorb 400 to 550g of deionized water per gram of dried hydrogel. Moreover, these hydrogels produced a strong antibacterial effect, which can be useful in developing new superabsorbent antimicrobial pharmaceutical products.
      Graphical abstract image

      PubDate: 2016-08-26T11:07:05Z
      DOI: 10.1016/j.jinorgbio.2016.08.007
       
  • The effects of the glycation of transferrin on chromium binding and the
           transport and distribution of chromium In Vivo
    • Authors: Ge Deng; Samantha L. Dyroff; Molly Lockart; Michael K. Bowman; John B. Vincent
      Abstract: Publication date: Available online 25 August 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Ge Deng, Samantha L. Dyroff, Molly Lockart, Michael K. Bowman, John B. Vincent
      Chromium (III) has been shown to act as a pharmacological agent improving insulin sensitivity in rodent models of obesity, insulin resistance, and diabetes. To act in beneficial fashion, chromium must reach insulin-sensitive tissues. Chromium is transported from the bloodstream to the tissues by the iron-transport protein transferrin. When blood concentrations of glucose are high (as in a diabetic subject), transferrin can be glycated, modifying its ability to bind and transport iron. However, the effects of glycation of transferrin on its ability to bind and transport Cr have not been examined previously. Storage of transferrin at 37°C in the presence and absence of glucose has significant effects on the binding of Cr. Transferrin stored in the absence of glucose only binds one equivalent of Cr tightly, compared to the normal binding of two equivalents of Cr by transferrin. Glycated transferrin (stored in the presence of glucose) binds two equivalents of Cr but the changes in its extinction coefficient at 245nm that accompany binding suggest that the Cr-bound transferrin possesses a conformation that deviates appreciably from untreated transferrin. These changes have dramatic effects, greatly reducing the ability of transferrin to transport Cr in vivo in rats. The results suggest that glycation of transferrin in subjects with high blood glucose concentrations should reduce the ability of Cr from pharmacological agents to enter tissues.
      Graphical abstract image

      PubDate: 2016-08-26T11:07:05Z
      DOI: 10.1016/j.jinorgbio.2016.08.008
       
  • The Heme-Based Oxygen Sensor Rhizobium etli FixL: Influence of Auxiliary
           Ligands on Heme Redox Potential and Implications on the Enzyme Activity
    • Authors: Nathalie Honorio-Felício; Marta S.P. Carepo; Tércio de F. Paulo; Luiz Gonzaga de França Lopes; Eduardo H.S. Sousa; Izaura C.N. Diógenes; Paul V. Bernhardt
      Abstract: Publication date: Available online 26 August 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Nathalie Honorio-Felício, Marta S.P. Carepo, Tércio de F. Paulo, Luiz Gonzaga de França Lopes, Eduardo H.S. Sousa, Izaura C.N. Diógenes, Paul V. Bernhardt
      Conformational changes associated to sensing mechanisms of heme-based protein sensors are a key molecular event that seems to modulate not only the protein activity but also the potential of the FeIII/II redox couple of the heme domain. In this work, midpoint potentials (E m) assigned to the FeIII/II redox couple of the heme domain of FixL from Rhizobium etli (ReFixL) in the unliganded and liganded states were determined by spectroelectrochemistry in the presence of inorganic mediators. In comparison to the unliganded ReFixL protein (+19mV), the binding to ligands that switch off the kinase activity induces a negative shift, i. e. E m =−51, −57 and −156mV for O2, imidazole and CN−, respectively. Upon binding to CO, which does not affect the kinase active, E m was observed at +21mV. The potential values observed for FeIII/II of the heme domain of ReFixL upon binding to CO and O2 do not follow the expected trend based on thermodynamics, assuming that positive potential shift would be expected for ligands that bind to and therefore stabilize the FeII state. Our results suggest that the conformational changes that switch off kinase activity upon O2 binding have knock-on effects to the local environment of the heme, such as solvent rearrangement, destabilize the FeII state and counterbalances the FeII-stabilizing influence of the O2 ligand.
      Graphical abstract image

      PubDate: 2016-08-26T11:07:05Z
      DOI: 10.1016/j.jinorgbio.2016.08.009
       
 
 
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