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  Subjects -> CHEMISTRY (Total: 792 journals)
    - ANALYTICAL CHEMISTRY (47 journals)
    - CHEMISTRY (552 journals)
    - CRYSTALLOGRAPHY (22 journals)
    - ELECTROCHEMISTRY (24 journals)
    - INORGANIC CHEMISTRY (41 journals)
    - ORGANIC CHEMISTRY (42 journals)
    - PHYSICAL CHEMISTRY (64 journals)

INORGANIC CHEMISTRY (41 journals)

Acta Polymerica     Hybrid Journal   (Followers: 6)
Additives for Polymers     Full-text available via subscription   (Followers: 21)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 4)
Advances in Polymer Technology     Hybrid Journal   (Followers: 12)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 2)
Bioinorganic Chemistry and Applications     Open Access   (Followers: 4)
Comments on Inorganic Chemistry: A Journal of Critical Discussion of the Current Literature     Hybrid Journal  
Current Methods in Inorganic Chemistry     Full-text available via subscription  
European Journal of Inorganic Chemistry     Hybrid Journal   (Followers: 6)
European Polymer Journal     Hybrid Journal   (Followers: 41)
Heterocyclic Communications     Full-text available via subscription   (Followers: 2)
High Performance Polymers     Hybrid Journal  
Indian Journal of Chemistry - Section A     Open Access   (Followers: 5)
Inorganic Chemistry     Full-text available via subscription   (Followers: 19)
Inorganic Chemistry Communications     Hybrid Journal   (Followers: 7)
Inorganic Chemistry Frontiers     Full-text available via subscription  
Inorganic Materials     Hybrid Journal   (Followers: 2)
Inorganic Materials: Applied Research     Hybrid Journal   (Followers: 1)
Inorganica Chimica Acta     Hybrid Journal   (Followers: 4)
Inorganics     Open Access  
International Journal of Inorganic Chemistry     Open Access   (Followers: 1)
JBIC Journal of Biological Inorganic Chemistry     Hybrid Journal   (Followers: 2)
Journal of Inorganic and Organometallic Polymers and Materials     Partially Free   (Followers: 6)
Journal of Inorganic Biochemistry     Hybrid Journal   (Followers: 2)
Journal of Inorganic Chemistry     Open Access  
Journal of Polymer Engineering     Full-text available via subscription   (Followers: 8)
Journal of Polymers and the Environment     Hybrid Journal   (Followers: 3)
Journal of Separation Science     Hybrid Journal   (Followers: 7)
Metallodrugs     Open Access  
Open Journal of Inorganic Chemistry     Open Access   (Followers: 1)
Plasmas and Polymers     Hybrid Journal  
Polymer Bulletin     Hybrid Journal   (Followers: 7)
Polymer Composites     Hybrid Journal   (Followers: 8)
Polyoxometalate Chemistry     Open Access  
Reviews in Inorganic Chemistry     Full-text available via subscription  
Russian Journal of Inorganic Chemistry     Hybrid Journal  
Studies in Inorganic Chemistry     Full-text available via subscription  
Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry     Hybrid Journal   (Followers: 3)
Topics in Inorganic and General Chemistry     Full-text available via subscription  
Zeitschrift für anorganische und allgemeine Chemie     Hybrid Journal   (Followers: 1)
Zeitschrift für Kristallographie - New Crystal Structures     Open Access  
Journal Cover Journal of Inorganic Biochemistry
   [4 followers]  Follow    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
     ISSN (Print) 0162-0134
     Published by Elsevier Homepage  [2571 journals]   [SJR: 0.807]   [H-I: 79]
  • Editorial Board
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141




      PubDate: 2014-10-17T09:58:46Z
       
  • CON
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141




      PubDate: 2014-10-17T09:58:46Z
       
  • Bioinorganic chemistry of synucleinopathies: Deciphering the binding
           features of Met motifs and His-50 in AS–Cu(I) interactions
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Marco C. Miotto , Andrés Binolfi , Markus Zweckstetter , Christian Griesinger , Claudio O. Fernández
      The aggregation of alpha-synuclein (AS) is a critical step in the etiology of Parkinson's disease (PD) and other neurodegenerative synucleinopathies. This process is selectively enhanced by copper in vitro and the interaction is proposed to play a potential role in vivo. Presently, the identity of the Cu(I) binding sites in AS and their relative affinities are under debate. In this work we have addressed unresolved details related to the structural binding specificity and affinity of Cu(I) to full-length AS. We demonstrated conclusively that: (i) the binding preferences of Cu(I) for the Met-binding sites at the N- (K d =20μM) and C-terminus (K d =270μM) of AS are widely different: (ii) the imidazole ring of His-50 acts as an effective anchoring residue (K d =50μM) for Cu(I) binding to AS; and (iii) no major structural rearrangements occur in the protein upon Cu(I) binding. Overall, our work shows that Cu(I) binding to the N- and C-terminal regions of AS are two independent events, with substantial differences in their affinities, and suggest that protein oxidative damage derived from a misbalance in cellular copper homeostasis would target preferentially the N-terminal region of AS. This knowledge is key to understanding the structural-aggregation basis of the copper catalyzed oxidation of AS.
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      PubDate: 2014-10-17T09:58:46Z
       
  • Introduction of a covalent histidine–heme linkage in a hemoglobin: A
           promising tool for heme protein engineering
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Selena L. Rice , Matthew R. Preimesberger , Eric A. Johnson , Juliette T.J. Lecomte
      The hemoglobins of the cyanobacteria Synechococcus and Synechocystis (GlbNs) are capable of spontaneous and irreversible attachment of the b heme to the protein matrix. The reaction, which saturates the heme 2-vinyl by addition of a histidine residue, is reproduced in vitro by preparing the recombinant apoprotein, adding ferric heme, and reducing the iron to the ferrous state. Spontaneous covalent attachment of the heme is potentially useful for protein engineering purposes. Thus, to explore whether the histidine–heme linkage can serve in such applications, we attempted to introduce it in a test protein. We selected as our target the heme domain of Chlamydomonas eugametos LI637 (CtrHb), a eukaryotic globin that exhibits less than 50% sequence identity with the cyanobacterial GlbNs. We chose two positions, 75 in the FG corner and 111 in the H helix, to situate a histidine near a vinyl group. We characterized the proteins with gel electrophoresis, absorbance spectroscopy, and NMR analysis. Both T111H and L75H CtrHbs reacted upon reduction of the ferric starting material containing cyanide as the distal ligand to the iron. With L75H CtrHb, nearly complete (>90%) crosslinking was observed to the 4-vinyl as expected from the X-ray structure of wild-type CtrHb. Reaction of T111H CtrHb also occurred at the 4-vinyl, in a 60% yield indicating a preference for the flipped heme orientation in the starting material. The work suggests that the His–heme modification will be applicable to the design of proteins with a non-dissociable heme group.
      Graphical abstract image

      PubDate: 2014-10-17T09:58:46Z
       
  • CYP2J2 epoxygenase membrane anchor plays an important role in facilitating
           electron transfer from CPR
    • Abstract: Publication date: January 2015
      Source:Journal of Inorganic Biochemistry, Volume 142
      Author(s): Daryl D. Meling , Daniel R. McDougle , Aditi Das
      CYP2J2 epoxygenase is a membrane-bound cytochrome P450 primarily expressed in the heart and plays a significant role in cardiovascular diseases. The interactions of CYP2J2 with its redox partner, cytochrome P450 reductase (CPR), and with its substrates are quite complex and can have a significant effect on the kinetics of substrate metabolism. Here we show that the N-terminus of CYP2J2 plays an important role in the formation of CYP–CPR complex for subsequent electron transfer. We demonstrate that when CYP2J2–CPR are pre-incubated before the onset of reduction, the kinetics of reduction is triphasic and is of a similar order of magnitude to previously reported rates in other cytochrome P450 systems. However, when CYP2J2 and CPR form a complex during the time course of the experiment the kinetics of the fastest phase for N-terminus containing full-length CYP2J2 is 200 times faster than the kinetics of reduction of N-terminally truncated CYP2J2. Hence, we show that the N-terminus of CYP2J2 is very important to form a productive CYP–CPR complex to facilitate electron transfer.
      Graphical abstract image

      PubDate: 2014-10-17T09:58:46Z
       
  • Semax, an ACTH4-10 peptide analog with high affinity for copper(II) ion
           and protective ability against metal induced cell toxicity
    • Abstract: Publication date: January 2015
      Source:Journal of Inorganic Biochemistry, Volume 142
      Author(s): Giovanni Tabbì , Antonio Magrì , Alessandro Giuffrida , Valeria Lanza , Giuseppe Pappalardo , Irina Naletova , Vincenzo Giuseppe Nicoletti , Francesco Attanasio , Enrico Rizzarelli
      Heptapeptide Semax, encompassing the sequence 4-7 of N-terminal domain of the adrenocorticotropic hormone (ACTH) and a C-terminal Pro-Gly-Pro tripeptide, belongs to a short regulatory peptides family. This compound has been found to affect learning processes and to exert marked neuroprotective activities on cognitive brain functions. Dys-homeostasis of metal ions is involved in several neurodegenerative disorders and growing evidences have showed that brain is a specialized organ able to concentrate metal ions. In this work, the metal binding ability and protective activity of Semax and its metal complexes were studied. The equilibrium study clearly demonstrated the presence of three complex species. Two minor species [CuL] and [CuLH−1]− co-exist together with the [CuLH−2]2− in the pH range from 3.6 to 5. From pH5 the [CuLH−2]2− species becomes predominant with the donor atoms around copper arranged in a 4N planar coordination mode. Noteworthy, a reduced copper induced cytotoxicity was observed in the presence of Semax by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay on a SHSY5Y neuroblastoma and RBE4 endothelial cell lines.
      Graphical abstract image

      PubDate: 2014-10-12T06:34:49Z
       
  • An investigation into the interactions of gold nanoparticles and
           anti-arthritic drugs with macrophages, and their reactivity towards
           thioredoxin reductase
    • Abstract: Publication date: January 2015
      Source:Journal of Inorganic Biochemistry, Volume 142
      Author(s): Lloyd R.A. James , Zhi-Qiang Xu , Ronald Sluyter , Emma L. Hawksworth , Celine Kelso , Barry Lai , David J. Paterson , Martin D. de Jonge , Nicholas E. Dixon , Jennifer L. Beck , Stephen F. Ralph , Carolyn T. Dillon
      Gold(I) complexes are an important tool in the arsenal of established approaches for treating rheumatoid arthritis (RA), while some recent studies have suggested that gold nanoparticles (Au NPs) may also be therapeutically efficacious. These observations prompted the current biological studies involving gold(I) anti-RA agents and Au NPs, which are aimed towards improving our knowledge of how they work. The cytotoxicity of auranofin, aurothiomalate, aurothiosulfate and Au NPs towards RAW264.7 macrophages was evaluated using the MTT assay, with the former compound proving to be the most toxic. The extent of cellular uptake of the various gold agents was determined using graphite furnace atomic absorption spectrometry, while their distribution within macrophages was examined using microprobe synchrotron radiation X-ray fluorescence spectroscopy. The latter technique showed accumulation of gold in discrete regions of the cell, and co-localisation with sulfur in the case of cells treated with aurothiomalate or auranofin. Electrospray ionization mass spectrometry was used to characterize thioredoxin reductase (TrxR) in which the penultimate selenocysteine residue was replaced by cysteine. Mass spectra of solutions of TrxR and aurothiomalate, aurothiosulfate or auranofin showed complexes containing bare gold atoms bound to the protein, or protein adducts containing gold atoms retaining some of their initial ligands. These results support TrxR being an important target of gold(I) drugs used to treat RA, while the finding that Au NPs are incorporated into macrophages, but elicit little toxicity, indicates further exploration of their potential for treatment of RA is warranted.
      Graphical abstract image

      PubDate: 2014-10-12T06:34:49Z
       
  • Design, synthesis and SAR studies of novel 1,2-bis(aminomethyl)cyclohexane
           platinum(II) complexes with cytotoxic activity. Studies of interaction
           with DNA of iodinated seven-membered 1,4-diaminoplatinocycles
    • Abstract: Publication date: January 2015
      Source:Journal of Inorganic Biochemistry, Volume 142
      Author(s): Marina Gay , Ángel M. Montaña , Consuelo Batalla , Juan M. Mesas , María-Teresa Alegre
      A selected library of nine novel platinum(II) complexes having differently functionalized 1,2-bis(aminomethyl)cyclohexane carrier ligands with a 1,4-diamino framework and iodides as labile ligands have been synthesized and evaluated in vitro for their tumor cell growth inhibitory activity, in front of one pair of human carcinoma cell lines A2780 and A2780cisR. These cell lines were chosen based on studying all the known main mechanisms of resistance of cisplatin. A2780cisR cells are resistant through a combination of reduced drug transport enhanced DNA repair/tolerance and elevated glutathione (GSH) levels with respect to the parental A2780 cells. Most platinum complexes evaluated showed a very low resistant factor, up to 16 times lower than that of cisplatin, which indicates their ability to overcome the cisplatin resistance in ovarian cancer A2780cisR cells. Structure–activity studies have been performed in order to know the influence of the several organic functionalities (CC double bond, free OH group, MeO group, etc.) and the stereochemistry on the cytotoxic activity. Moreover, studies of interaction with DNA of these complexes were performed via three techniques: circular dichroism (CD), electrophoresis on agarose gel (EF) and atomic force microscopy (AFM) in order to evaluate the modifications of secondary and tertiary structure of DNA, induced by platinum complexes. These studies allowed us to correlate the IC50 values of complexes and the intensity of interaction to DNA, the main target for these compounds.
      Graphical abstract image

      PubDate: 2014-10-12T06:34:49Z
       
  • Selective interaction of Hpn-like protein with nickel, zinc and bismuth in
           vitro and in cells by FRET
    • Abstract: Publication date: January 2015
      Source:Journal of Inorganic Biochemistry, Volume 142
      Author(s): Yuen-Yan Chang , Yau-Tsz Lai , Tianfan Cheng , Haibo Wang , Ya Yang , Hongzhe Sun
      Hpn-like (Hpnl) is a unique histidine- and glutamine-rich protein found only in Helicobacter pylori and plays a role on nickel homeostasis. We constructed the fluorescent sensor proteins CYHpnl and CYHpnl_1-48 (C-terminal glutamine-rich region truncated) using enhanced cyan and yellow fluorescent proteins (eCFP and eYFP) as the donor–acceptor pair to monitor the interactions of Hpnl with metal ions and to elucidate the role of conserved Glu-rich sequence in Hpnl by fluorescence resonance energy transfer (FRET). CYHpnl and CYHpnl_1-48 exhibited largest responses towards Ni(II) and Zn(II) over other metals studied and the binding of Bi(III) to CYHpnl was observed in the presence of an excess amount of Bi(III) ions (K d =115±4.8μM). Moreover, both CYHpnl and CYHpnl_1-48 showed positive FRET responses towards the binding to Ni(II) and Zn(II) in Escherichia coli cells overexpressing CYHpnl and CYHpnl_1-48, whereas a decrease in FRET upon Bi(III)-binding in E. coli cells overexpressing the latter. Our study provides clear evidence on Hpnl binding to nickel in cells, and intracellular interaction of Hpnl with Bi(III) could disrupt the protein function, thus probably contributing to the efficacy of Bi(III) drugs against H. pylori.
      Graphical abstract image

      PubDate: 2014-10-08T05:58:58Z
       
  • 2,6-Bis(2,6-diethylphenyliminomethyl)pyridine coordination compounds with
           cobalt(II), nickel(II), copper(II), and zinc(II): synthesis, spectroscopic
           characterization, X-ray study and in vitro cytotoxicity
    • Abstract: Publication date: January 2015
      Source:Journal of Inorganic Biochemistry, Volume 142
      Author(s): Pablo Martinez-Bulit , Ariadna Garza-Ortíz , Edgar Mijangos , Lidia Barrón-Sosa , Francisco Sánchez-Bartéz , Isabel Gracia-Mora , Angelina Flores-Parra , Rosalinda Contreras , Jan Reedijk , Norah Barba-Behrens
      Coordination compounds with cobalt(II), nickel(II), copper(II) and zinc(II) and the ligand 2,6-bis(2,6-diethylphenyliminomethyl)pyridine (L) were synthesized and fully characterized by IR and UV–Vis-NIR spectroscopy, elemental analysis, magnetic susceptibility and X-ray diffraction for two representative cases. These novel compounds were designed to study their activity as anti-proliferative drugs against different human cancer cell lines. The tridentate ligand forms heptacoordinated compounds from nitrate metallic salts, where the nitrate acts in a chelating form to complete the seven coordination positions. In vitro cell growth inhibition was measured for CoII, CuII and ZnII complexes, as well as for the free ligand. Upon coordination, the IC50 value of the transition-metal compounds is improved compared to the free ligand. The copper(II) and zinc(II) compounds are the most promising candidates for further in vitro and in vivo studies. The activity against colon and prostate cell lines merits further research, in views of the limited therapeutic options for such cancer types.
      Graphical abstract image

      PubDate: 2014-10-08T05:58:58Z
       
  • Ruthenium(II) polypyridyl complexes induce BEL-7402 cell apoptosis by
           ROS-mediated mitochondrial pathway
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Guang-Bin Jiang , Xiang Zheng , Jun-Hua Yao , Bing-Jie Han , Wei Li , Ji Wang , Hong-Liang Huang , Yun-Jun Liu
      A new ligand dmdppz and its four ruthenium(II) polypyridyl complexes [Ru(dmb)2(dmdppz)](ClO4)2 (1), [Ru(bpy)2(dmdppz)](ClO4)2 (2), [Ru(phen)2(dmdppz)](ClO4)2 (3) and [Ru(dmp)2(dmdppz)](ClO4)2 (4) (where dmb, bpy, phen, dmp and dmdppz stand for 4,4′-dimethyl-2,2′-bipyridine, 2,2′-bipyridine, 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline and 5,8-dimethoxylpyrido[3,2-a:2′,3′-c]phenazine, respectively) have been synthesized and characterized. Their DNA binding behaviors show that the complexes bind to calf thymus DNA by intercalation. The complexes exhibit efficient photocleavage of pBR322 DNA on irradiation. The cytotoxicity of the ligand and the complexes toward HepG-2, HeLa, MG-63, A549 and BEL-7402 were assayed by MTT ((3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide)) method. The IC50 values of the complexes 1, 2, 3 and 4 toward BEL-7402 cells are 14.6, 16.8, 18.0 and 16.7μM, respectively. Dmdppz shows no cytotoxic activity against selected cell lines. The cellular uptake, apoptosis, comet assay, reactive oxygen species (ROS), mitochondrial membrane potential and western blot analysis were investigated. These results indicate that complexes 1–4 exert their toxicity through the intrinsic ROS-mediated mitochondrial pathway, which is accompanied by the regulation of Bcl-2 family proteins.
      Graphical abstract image

      PubDate: 2014-10-03T05:38:13Z
       
  • Cytotoxic malonate platinum(II) complexes with
           1,2,4-triazolo[1,5-a]pyrimidine derivatives: Structural characterization
           and mechanism of the suppression of tumor cell growth
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Iwona Łakomska , Kamil Hoffmann , Andrzej Wojtczak , Jerzy Sitkowski , Ewa Maj , Joanna Wietrzyk
      A series of malonate (mal) platinum(II) complexes of the general formula [Pt(mal)(L)2], where L=5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp) (1), 7-isobutyl-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine (ibmtp) (2) or 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) (3), has been prepared and characterized using multinuclear (1H, 13C, 15N, 195Pt) NMR, IR and electrospray ionization mass spectrometry (ESIMS). Furthermore, the crystal structures of [Pt(mal)(dmtp)2]∙4H2O (1a) and [Pt(mal)(dbtp)2]∙CHCl3 (3a) have been determined using single-crystal X-ray diffraction. The spectroscopic characterization unambiguously confirmed the square-planar geometry of Pt(II) with two monodentate N3-bonded 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines and one O-chelating malonate. The antiproliferative activities of the compounds against the human cell lines T47D (cisplatin-resistant human ductal breast epithelial tumor cell line) and A549 (lung adenocarcinoma epithelial cell line) and the mouse cell line 4T1 (mouse breast tumor model) were assessed using an in vitro screening assay. Compounds (2) and (3) exhibited substantial antigrowth properties against T47D cells, whereas only (3) exhibited an IC50 value that was lower than cisplatin and carboplatin against the 4T1 cell line. Additionally, compounds (2, 3) are capable of arresting the cell cycle of A549 cells at the G0/G1 phase, whereas cisplatin and carboplatin arrested the cells at the G2/M phase, indicating differences in the mechanism of the suppression of tumor cell growth. Finally, in the quest for low toxicity platinum drugs, the in vitro antiproliferative activity against normal mouse fibroblast cells (BALB/3T3) was evaluated. The inhibition of BALB/3T3 cell proliferation by the evaluated Pt(II) complexes increased in the order (1)<(2)<<carboplatin<<(3)<cisplatin.
      Graphical abstract image

      PubDate: 2014-10-03T05:38:13Z
       
  • Syntheses, crystal structures and antioxidant study of Zn(II) complexes
           with morin-5′-sulfonic acid (MSA)
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Elżbieta Pieniążek , Jan Kalembkiewicz , Maciej Dranka , Elżbieta Woźnicka
      The study of modified synthetic procedure of water soluble morin-5′-sulfonic acid sodium salt (NaMSA) involving less aggressive chemicals and carried out at mild conditions was described. The NaMSA salt is a convenient source of anionic morin-5'-sulfonic ligand (MSA) in ion exchange reactions. The coordination ability of MSA ligand towards the zinc cations was investigated in aqueous solution and in solid state. Novel zinc complexes of morin-5'-sulfonate were obtained by a reaction of Zn(NO3)2 with morin-5'-sulfonate in water. Resulting compounds were characterized by single-crystal X-ray diffraction analysis, as well as spectral and thermal methods. The coordination interaction, hydrogen bond and π–π stacking lead to the formation of a 1D chain or 3D coordination polymers. The antioxidant activity of the Zn(II)–MSA complexes was evaluated by means of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method. In this work, we have shown that the studied compounds are more effective free radical scavengers than the natural flavonoids like plain morin.
      Graphical abstract image

      PubDate: 2014-10-03T05:38:13Z
       
  • Mercury binding by methanobactin from Methylocystis strain SB2
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Bipin S. Baral , Nathan L. Bandow , Alexy Vorobev , Brittani C. Freemeier , Brandt H. Bergman , Timothy J. Herdendorf , Nathalie Fuentes , Luke Ellias , Erick Turpin , Jeremy D. Semrau , Alan A. DiSpirito
      Methanobactin (mb) is a post-translationally modified copper-binding compound, or chalkophore, secreted by many methane-oxidizing bacteria or methanotrophs in response to copper limitation. In addition to copper, methanobactin from Methylosinus trichosporium OB3b (mb-OB3b) has been shown to bind a variety of metals including Hg2+. In this report, Hg binding by the structurally unique methanobactin from Methylocystis strain SB2 (mb-SB2) was examined and compared to mb-OB3b. Mb-SB2 is shown to bind the common forms of Hg found in aqueous environments, Hg2+, Hg(CN)2 and CH3Hg+. The spectral and thermodynamic properties of binding for each form of mercury differed. UV-visible absorption spectra suggested that Hg2+ binds to both the oxazolone and imidazolone rings of mb-SB2, whereas CH3Hg+ appeared to only bind to the oxazolone ring. Hg(CN)2 showed spectral properties between Hg2+ and CH3Hg+. Isothermal titration calorimetry (ITC) showed both Hg(CN)2 and CH3Hg+ fit into two-site binding models. For Hg(CN)2 the first site was exothermic and the second endothermic. Both binding sites in CH3Hg+ were exothermic, but at equilibrium the reaction never moved back to the baseline, suggesting a slow residual reaction. ITC results for Hg2+ were more complex and suggested a 3- or 4-site model. The spectral, kinetic and thermodynamic changes following Hg binding by mb-SB2 also differed from the changes associated with mb-OB3b. Like mb-OB3b, copper did not displace Hg bound to mb-SB2. In contrast to mb-OB3b Hg2+ could displace Cu from Cu-containing mb-SB2 and preferentially bound Hg2+ over Cu2+ at metal to mb-SB2 molar ratios above 1.0.
      Graphical abstract image

      PubDate: 2014-09-29T05:21:01Z
       
  • Mercury metallation of the copper protein azurin and structural insight
           into possible heavy metal reactivity
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Anthony P. Zampino , Francesca M. Masters , Erika L. Bladholm , Matthew J. Panzner , Steven M. Berry , Thomas C. Leeper , Christopher J. Ziegler
      Mercury(II) metallation of Pseudomonas aeruginosa azurin has been characterized structurally and biochemically. The X-ray crystal structure at 1.5Å of mercury(II) metallated azurin confirms the coordination of mercury at the copper binding active site and a second surface site. These findings are further validated by NMR, Matrix-assisted laser desorption/ionization spectrometry (MALDI), and UV–visible spectroscopic methods indicating copper displacement from the wild-type protein. Bioinformatic analysis has identified homologous human protein domains computationally, and compared them to the structure of azurin, providing a model for human mercury interactions. Study of the mercury–azurin adduct, in combination with other known examples of protein–heavy metal interactions, could provide further insight into the chemical mechanisms of toxicological interactions, leading toward a global understanding of the biological speciation of toxic heavy metals.
      Graphical abstract image

      PubDate: 2014-09-29T05:21:01Z
       
  • Ferrocifen derivatives that induce senescence in cancer cells: selected
           examples
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Céline Bruyère , Véronique Mathieu , Anne Vessières , Pascal Pigeon , Siden Top , Gérard Jaouen , Robert Kiss
      Platinum coordination complexes represent an important class of anti-tumor agents. Due to recognized drawbacks, research into other types of metallodrugs has been diversified with the aim of finding new chemical entities with alternative mechanisms of action to overcome classical chemoresistance. P5 and DP1, two closely related ferrocenyl complexes bearing a similar ferrocenyl-ene-phenyl motif and displaying marked differences in their conformations and oxidation state versatility, were assayed in cancer cell models characterized by various sensitivities to pro-apoptotic stimuli. P5 and DP1 exert growth inhibitory effects between 0.5 and 10μM against glioma and melanoma cells including pluripotent stem-like cells. These effects are due, at least partly, to senescence induction with typical SA-β-galactosidase staining and senescence-associated secretory phenotype (SASP) as measured by the secretion of IL-1α, IL-1β, IL-6, IL-8 and TNF-α. Regulation of these cytokines' secretion may be related to AP-1 and other transcription factors unrelated to senescence. An in vivo graft of B16F10 cells after in vitro pre-incubation with DP1 or P5 led to increased survival in mice. In conclusion, P5 and DP1 ferrocenyl complexes induce senescence in various cancer cell models associated with distinct sensitivity to pro-apoptotic stimuli.
      Graphical abstract image Highlights This study reports that synthetic ferrocenyl complexes can overcome apoptosis resistance by inducing irreversible senescence associated with a typical secretory phenotype. However and interestingly this senescence occurs via an unclassical pathway.

      PubDate: 2014-09-29T05:21:01Z
       
  • A new bis-3-hydroxy-4-pyrone as a potential therapeutic iron chelating
           agent. Effect of connecting and side chains on the complex structures and
           metal ion selectivity
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Valeria M. Nurchi , Guido Crisponi , Massimiliano Arca , Miriam Crespo-Alonso , Joanna I. Lachowicz , Delara Mansoori , Leonardo Toso , Giuseppina Pichiri , M. Amelia Santos , Sergio M. Marques , Juan Niclós-Gutiérrez , Josefa M. González-Pérez , Alicia Domínguez-Martín , Duane Choquesillo-Lazarte , Zbigniew Szewczuk , M. Antonietta Zoroddu , Massimiliano Peana
      This work reports the synthesis, characterization and study of complex formation equilibria of the new ligand 6,6′-(2-(diethylamino)ethylazanediyl)bis(methylene)bis(5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) with FeIII, AlIII, CuII and ZnII. On the basis of previous encouraging results with tetradentate bis-kojic acid chelators, this ligand was designed to improve the pharmacokinetic properties: increase the solubility, neutral at physiological pH7.4, and enhancement of membrane crossing ability. FeIII and AlIII complexation gave evidence of high metal-sequestering capacity of L9. Cellular assays showed that the ligand is capable of crossing cellular membranes and it does not present toxic effects. Complex formation equilibria with the essential metal ions CuII and ZnII have been furthermore studied to evaluate disturbances of this chelator on the homeostatic equilibria of these essential metal ions. A variety of techniques (potentiometry, UV–visible spectrophotometry, 1D and 2D NMR spectroscopy, ESI–MS (electrospray ionization–mass spectrometry), quantum mechanical calculations and X-ray diffraction) have facilitated the characterization of the ligand, and the corresponding iron and zinc complexes, together with an exhaustive analysis of the protonation and complex equilibria.
      Graphical abstract image

      PubDate: 2014-09-25T04:59:30Z
       
  • Editorial Board
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140




      PubDate: 2014-09-21T04:20:47Z
       
  • Contents
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140




      PubDate: 2014-09-21T04:20:47Z
       
  • α-Hydroxy coordination of mononuclear vanadyl citrate, malate and
           S-citramalate with N-heterocycle ligand, implying a new protonation
           pathway of iron–vanadium cofactor in nitrogenase
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Can-Yu Chen , Mao-Long Chen , Hong-Bin Chen , Hongxin Wang , Stephen P. Cramer , Zhao-Hui Zhou
      Unlike the most of α-alkoxy coordination in α-hydroxycarboxylates to vanadium, novel α-hydroxy coordination to vanadium(IV) has been observed for a series of chiral and achiral monomeric α-hydroxycarboxylato vanadyl complexes [VO(H2cit)(bpy)]·2H2O (1), [VO(Hmal)(bpy)]·H2O (2), [VO(H2cit)(phen)]·1.5H2O (3), [VO(Hmal)(phen)]·H2O (4), and [ΔVO(S-Hcitmal)(bpy)]·2H2O (5), [VO(H2cit)(phen)]2·6.5H2O (6), which were isolated from the reactions of vanadyl sulfate with α-hydroxycarboxylates and N-heterocycle ligands in acidic solution. The complexes feature a tridentate citrate, malate or citramalate that chelates to vanadium atom through their α-hydroxy, α-carboxy and β-carboxy groups; while the other β-carboxylic acidic group of citrate is free to participate strong hydrogen bonds with lattice water molecule. The neutral α-hydroxy group also forms strong intermolecular hydrogen bonds with water molecule and the negatively-charged α-carboxy group in the environment. The inclusion of a hydrogen ion in α-alkoxy group results in the formation of a series of neutral complexes with one less positive charge. There are two different configurations of citrate with respect to the trans-position of axial oxo group, where the complex with trans-hydroxy configuration seems more stable with less hindrance. The average bond distances of VOhydroxy and VOα-carboxy are 2.196 and 2.003Å respectively, which are comparable to the VO distance (2.15Å) of homocitrate in FeV-cofactor of V-nitrogenase. A new structural model is suggested for R-homocitrato iron vanadium cofactor as VFe7S9C(R-Hhomocit) (H4homocit=homocitric acid) with one more proton in homocitrate ligand.
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      PubDate: 2014-09-21T04:20:47Z
       
  • Synthesis, characterization, and antitumor activity of unusual pseudo five
           coordinate gold(III) complexes: Distinct cytotoxic mechanism or expensive
           ligand delivery systems?
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Pauline M. Olsen , Charles Ruiz , Daniel Lussier , Brian Khoa Le , Noah Angel , Michelle Smith , Chihyun (Brian) Hwang , Raneen Khatib , Julia Jenkins , Kaitlyn Adams , Jonathan Getcher , Fook Tham , Zhou (Georgia) Chen , Emma H. Wilson , Jack F. Eichler
      Gold(III) complexes bearing bidentate ligands based on the 1,10-phenanthroline and 2,2′-bipyridine scaffolds have shown promising anticancer activity against a variety of tumor cell lines. In particular, our laboratory has previously found that a pseudo five coordinate gold(III) complex possessing the 2,9-di-sec-butyl-1,10-phenanthroline ligand {[(di-sec-butylphen)AuCl3]} exhibits antitumor activity against a panel of five different lung and head–neck tumor cell lines. However, the [(di-sec-butylphen)AuCl3] complex was determined to be less active than the free 2,9-di-sec-butyl-1,10-phenanthroline ligand. In order to determine if this class of gold(III) complexes has a distinct mechanism of initiating tumor cell death or if these gold complexes simply release the polypyridyl ligand in the intracellular environment, structural analogues of the [(di-sec-butylphen)AuCl3] complex have been synthesized and structurally characterized. These structural congeners were prepared by using mono-alkyl and di-phenyl substituted 1,10-phenanthroline ligands, di-alkyl and di-phenyl substituted 4-methyl-1,10-phenanthroline ligands, and mono-alkyl 2,2′-bipyridine ligands. The redox stability of this library of distorted square pyramidal gold(III) complexes has been studied and the in vitro antitumor activity of gold(III) complexes and corresponding polypyridyl ligands has been determined. The [(di-n-butylphen)AuCl3] and [(mono-n-butylphen)AuCl3] complexes have been found to be significantly more potent at inhibiting the growth of A549 lung tumor cells than the clinically used drug cisplatin. More importantly, these two gold(III) complexes are significantly more active than their respective free ligands, providing evidence that this class of pseudo five coordinate gold(III) complexes has a mechanism of initiating tumor cell death that is independent of the free ligand.
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      PubDate: 2014-09-21T04:20:47Z
       
  • Synthesis and biological evaluation of 2-benzoylpyridine
           thiosemicarbazones in a dimeric system: Structure–activity
           relationship studies on their anti-proliferative and iron chelation
           efficacy
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Adeline Y. Lukmantara , Danuta S. Kalinowski , Naresh Kumar , Des R. Richardson
      Thiosemicarbazone chelators represent an exciting class of biologically active compounds that show great potential as anti-tumor agents. Our previous studies demonstrated the potent anti-tumor activity of the 2′-benzoylpyridine thiosemicarbazone series. While extensive studies have been performed on monomeric thiosemicarbazone compounds, dimeric thiosemicarbazone chelators have received comparatively less attention. Thus, it was of interest to investigate the anti-proliferative activity and iron chelation efficacy of dimeric thiosemicarbazones. Two classes of dimeric thiosemicarbazones were designed and synthesized. The first class consisted of two benzoylpyridine-based thiosemicarbazone units connected via a hexane or dodecane alkyl bridge, while the second class of dimer consisted of two thiosemicarbazones attached to a 2,6-dibenzoylpyridine core. These dimeric ligands demonstrated greater anti-proliferative activity than the clinically used iron chelator, desferrioxamine. This study highlights the importance of optimal lipophilicity as a factor influencing the cytotoxicity and iron chelation efficacy of these chelators.
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      PubDate: 2014-09-18T04:11:17Z
       
  • Combining anti-cancer drugs with artificial sweeteners: Synthesis and
           anti-cancer activity of saccharinate (sac) and thiosaccharinate (tsac)
           complexes cis-[Pt(sac)2(NH3)2] and cis-[Pt(tsac)2(NH3)2]
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Subhi A. Al-Jibori , Ghassan H. Al-Jibori , Lamaan J. Al-Hayaly , Christoph Wagner , Harry Schmidt , Suna Timur , F. Baris Barlas , Elif Subasi , Shishir Ghosh , Graeme Hogarth
      The new platinum(II) complexes cis-[Pt(sac)2(NH3)2] (sac=saccharinate) and cis-[Pt(tsac)2(NH3)2] (tsac=thiosaccharinate) have been prepared, the X-ray crystal structure of cis-[Pt(sac)2(NH3)2].H2O reveals that both saccharinate anions are N-bound in a cis-arrangement being inequivalent in both the solid-state and in solution at room temperature. Preliminary anti-cancer activity has been assessed against A549 human alveolar type-II like cell lines with the thiosaccharinate complex showing good activity.
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      PubDate: 2014-09-18T04:11:17Z
       
  • A hybrid antioxidizing and antibacterial material based on Ag–La2O3
           nanocomposites
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Kunjie Wang , Yanping Wu , Hongxia Li , Mingliang Li , Feng Guan , Haiyan Fan
      The Ag–La2O3 hybrid nanoparticles were prepared by loading Ag nanoparticles on the surface of the La2O3 nanorods. The synthesis was a one-step process where sodium borohydride was used as a reducing agent to convert silver ions into silver nanoparticles, which were further deposited on the La2O3 nanorods. Moreover, they were found evenly dispersed upon the surface of La2O3 supports. The as-prepared Ag–La2O3 nanocomposites showed anti-oxidizing and significant antibacterial effect in vitro. Using the results from transmission electron microscope (TEM), the plausible mechanism was also proposed to explain the inhibition of bacterial growth. The present strategy can be potentially extended to develop drug-labels and other antibacterial agents.
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      PubDate: 2014-09-18T04:11:17Z
       
  • Novel copper(II) complexes as new promising antitumour agents. A crystal
           structure of [Cu(1,10-phenanthroline-5,6-dione)2(OH2)(OClO3)](ClO4)
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Tiziana Pivetta , Federica Trudu , Elisa Valletta , Francesco Isaia , Carlo Castellano , Francesco Demartin , Rossana Tuveri , Sarah Vascellari , Alessandra Pani
      The cytotoxic properties of copper(II) complexes with 1,10-phenanthroline (phen) can be modified by substitution in the phen backbone. For this purpose, Cu(II) complexes with phen, 1,10-phenanthrolin-5,6-dione (phendione) and 1,10-phenanthrolin-5,6-diol (phendiol) have been synthesised and characterised. The crystal structure of [Cu(phendione)2(OH2)(OClO3)](ClO4) is discussed. The complex formation equilibria between Cu(II) and phen or phendione were studied by potentiometric measurements at 25 and 37°C in 0.1M ionic strength (NaCl). The antitumour activity of the compounds has been tested in vitro against a panel of tumour (DU-145, HEP-G2, SK-MES-1, CCRF-CEM, CCRF-SB) and normal (CRL-7065) human cell lines. The studied compounds generally present an antiproliferative effect greater than that of cisplatin. The phen and phendione ligands present a similar antiproliferative effect against all the tested cells. Phendiol presents an antiproliferative effect 1.3 to 18 times greater than that of phen or phendione for leukemic, lung, prostatic and fibroblast cells, while it presents less activity towards hepatic cells. Complexes with two ligands are more cytotoxic towards all the tested cell lines than complexes with one ligand and are generally more cytotoxic than the ligand alone. Complexes [Cu(phendiol)2(OH2)](ClO4)2 and [Cu(phendione)2(OH2)(OClO3)](ClO4) appear to be the most active compounds for the treatment of SK-MES-1 and HEP-G2 cells, respectively, being at least 18 times more cytotoxic than cisplatin. The studied Cu(II) complexes are characterised by a strong DNA affinity and were found to interact with DNA mainly by groove binding or electrostatic interactions. The complexes appear to act on cells with a mechanism different from that of cisplatin.
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      PubDate: 2014-09-18T04:11:17Z
       
  • Synthesis and biological assays on cancer cells of dinuclear gold
           complexes with novel functionalised di(N-heterocyclic carbene) ligands
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Marco Baron , Stéphane Bellemin-Laponnaz , Cristina Tubaro , Marino Basato , Sara Bogialli , Alessandro Dolmella
      New dinuclear di(N-heterocyclic carbene) silver(I), gold(I) and gold(III) complexes have been synthesised and their antiproliferative effects towards various cancer cell lines have been screened. The di(N-heterocyclic carbene) ligands have a propylene linker between the carbene moieties and the imidazole backbone has been functionalised with a 1-benzyl- or 1-PEG-1,2,3-triazole ring (PEG=poly(ethylene glycol)) via a CuAAC (copper azido alkyne cycloaddition) reaction. The resulting gold(I) and gold(III) complexes display an antiproliferative activity superior to that of the unfunctionalised pristine complexes together with a higher selectivity towards cancerous cells with respect to healthy cells.
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      PubDate: 2014-09-18T04:11:17Z
       
  • Hydroxyquinoline derived vanadium(IV and V) and copper(II) complexes as
           potential anti-tuberculosis and anti-tumor agents
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Isabel Correia , Pedro Adão , Somnath Roy , Mohamed Wahba , Cristina Matos , Mannar R. Maurya , Fernanda Marques , Fernando R. Pavan , Clarice Q.F. Leite , Fernando Avecilla , João Costa Pessoa
      Several mixed ligand vanadium and copper complexes were synthesized containing 8-hydroxyquinoline (8HQ) and a ligand such as picolinato (pic−), dipicolinato (dipic2−) or a Schiff base. The complexes were characterized by spectroscopic techniques and by single-crystal X-ray diffraction in the case of [VVO(l-pheolnaph-im)(5-Cl-8HQ)] and [VVO(OMe)(8HQ)2], which evidenced the distorted octahedral geometry of the complexes. The electronic absorption data showed the presence of strong ligand to metal charge transfer bands, significant solvent effects, and methoxido species in methanol, which was further confirmed by 51V- NMR spectroscopy. The structures of [CuII(dipic)(8HQ)]Na and [VIVO(pic)(8HQ)] were confirmed by EPR spectroscopy, showing only one species in solution. The biological activity of the compounds was assessed through the minimal inhibitory concentration (MIC) of the compounds against Mycobacterium tuberculosis (Mtb) and the cytotoxic activity against the cisplatin sensitive/resistant ovarian cells A2780/A2780cisR and the non-tumorigenic HEK cells (IC50 values). Almost all tested vanadium complexes were very active against Mtb and the MICs were comparable to, or better than, the MICs of drugs, such as streptomycin. The activity of the complexes against the A2780 cell line was dependent on incubation time presenting IC50 values in the 3–14μM (at 48h) range. In these conditions, the complexes were significantly (*P <0.05–**P <0.001) more active than cisplatin (22μM), in the A2780 cells and even surpassing its activity in the cisplatin-resistant cells A2780cisR (2.4–8μM vs. 75.4; **P <0.001). In the non-tumorigenic HEK cells poor selectivity toward cancer cells for most of the complexes was observed, as well as for cisplatin.
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      PubDate: 2014-09-18T04:11:17Z
       
  • Selected cytotoxic gold compounds cause significant inhibition of 20S
           proteasome catalytic activities
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Nicola Micale , Tanja Schirmeister , Roberta Ettari , Maria A. Cinellu , Laura Maiore , Maria Serratrice , Chiara Gabbiani , Lara Massai , Luigi Messori
      Six structurally diverse cytotoxic gold compounds are reported to cause profound and differential inhibition of the three main catalytic activities of purified 20S proteasome whilst auranofin, an established gold(I) drug in clinical use, is nearly ineffective. In particular, the gold(I) complex [(pbiH)Au(PPh3 )]PF6 , turns out to be the most potent inhibitor of all three enzyme activities with sub-micromolar IC50 values. The present results further support the view that proteasome inhibition may play a major – yet not exclusive – role in the cytotoxic actions of gold based anticancer agents.
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      PubDate: 2014-09-18T04:11:17Z
       
  • Off–on–off pH luminescence switching and DNA binding
           properties of a free terpyridine-appended ruthenium complex
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Ze-Bao Zheng , Si-Yuan Kang , Xun Yi , Na Zhang , Ke-Zhi Wang
      A ruthenium(II) complex [Ru(bpy)2(HL1)](ClO4)2·3H2O {bpy=2,2′-bipyridine and HL1 =2-(2,6-di(pyridin-2-yl)pyridin-4-yl)-1H-imidazo[4,5-f][1,10]phenanthroline}, denoted as RuHL1 , was synthesized and characterized by elemental analysis, proton nuclear magnetic resonance spectroscopy, and mass spectrometry. The pH effects on the UV–visible (UV–vis) absorption and emission spectra and the luminescence lifetimes of RuHL1 have been studied, and their ground- and excited-state acid ionization constants were derived. The complex was found to exhibit pH-induced “off–on–off” luminescence switching properties via protonation/deprotonation of the grafted imidazole and terpyridyl groups. A pH-induced emission on–off intensity ratio of 166 was observed as pH was increased from 2.00 to 5.44, which is one of the largest values observed among imidazole-containing Ru(II) complex-based acidic-pH-induced pH luminescence switches. RuHL1 also strongly binds to calf thymus DNA in mixed binding modes involving classic intercalation and partial intercalation, as determined by UV–vis absorption and emission spectrophotometric DNA titration, ethidium bromide displacement, DNA denaturation and DNA viscosity measurements.
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      PubDate: 2014-09-18T04:11:17Z
       
  • Synthesis, characterization, microbiological evaluation, genotoxicity and
           synergism tests of new nano silver complexes with sulfamoxole X-ray
           diffraction of [Ag2(SMX)2]·DMSO
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Francesca Velluti , Natalia Mosconi , Ana Acevedo , Graciela Borthagaray , Jorge Castiglioni , Ricardo Faccio , Davi Fernando Back , Guillermo Moyna , Marcela Rizzotto , María H. Torre
      The synthesis and microbiological evaluation of two new Ag(I) complexes with sulfamoxole (SMX), [Ag2(SMX)2]·H2O and [Ag4(SCN)3(SMX)]·H2O are described. Both were characterized by elemental analysis, thermogravimetry, powder and single crystal X-ray diffraction, NMR, Raman and experimental and theoretical IR spectroscopies. Their antibacterial and antifungal properties were evaluated by agar and broth dilution assays, respectively. In addition, synergism tests for Pseudomonas aeruginosa were performed, and genotoxicity studies were carried out employing the Allium cepa test. Both complexes displayed good activity against Escherichia coli, Staphylococcus aureus, P. aeruginosa, and 10 fungi strains, with lower minimum inhibitory concentrations (MICs) than that of free SMX in all cases. The nanometrical crystallite particle size determined from XRPD, DLS and TEM might explain the good microbiological activity in spite of the low solubility of both complexes. The fractional inhibitory concentration (FIC) calculated from the P. aeruginosa test data indicated that the activity of the complexes is not due to synergism of the free components in the concentration ratios studied. Moreover, none of the complexes displayed cytotoxic effects on onions in the concentration range tested, and chromosome aberrations were not observed.
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      PubDate: 2014-09-18T04:11:17Z
       
  • Decomposition of amino diazeniumdiolates (NONOates): Molecular mechanisms
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Nizamuddin Shaikh , Marat Valiev , Sergei V. Lymar
      Although diazeniumdiolates (X[N(O)NO]−) are extensively used in biochemical, physiological, and pharmacological studies due to their ability to release NO and/or its congeneric nitroxyl, the mechanisms of these processes remain obscure. In this work, we used a combination of spectroscopic, kinetic, and computational techniques to arrive at a quantitatively consistent molecular mechanism for decomposition of amino diazeniumdiolates (amino NONOates: R2N[N(O)NO]−, where R= N(C2H5)2 (1), N(C3H4NH2)2 (2), or N(C2H4NH2)2 (3)). Decomposition of these NONOates is triggered by protonation of their [NN(O)NO]− group with the apparent pK a and decomposition rate constants of 4.6 and 1s−1 for 1; 3.5 and 0.083s−1 for 2; and 3.8 and 0.0033s−1 for 3. Although protonation occurs mainly on the O atoms of the functional group, only the minor R2N(H)N(O)NO tautomer (population ~10−7, for 1) undergoes the NN heterolytic bond cleavage (k d ~107 s−1 for 1) leading to amine and NO. Decompositions of protonated amino NONOates are strongly temperature-dependent; activation enthalpies are 20.4 and 19.4kcal/mol for 1 and 2, respectively, which includes contributions from both the tautomerization and bond cleavage. The bond cleavage rates exhibit exceptional sensitivity to the nature of R substituents which strongly modulate activation entropy. At pH<2, decompositions of all three NONOates that have been investigated are subject to additional acid catalysis that occurs through di-protonation of the [NN(O)NO]− group.
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      PubDate: 2014-09-18T04:11:17Z
       
  • Y3+, La3+, and some bivalent metals inhibited the opening of the
           Tl+-induced permeability transition pore in Ca2+-loaded rat liver
           mitochondria
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Sergey Korotkov , Svetlana Konovalova , Larisa Emelyanova , Irina Brailovskaya
      We showed earlier that diminution of 2,4-dinitrophenol (DNP)-stimulated respiration and increase of both mitochondrial swelling and electrochemical potential (ΔΨmito) dissipation in medium containing TlNO3 and KNO3 were caused by opening of Tl+-induced mitochondrial permeability transition pore (MPTP) in the inner membrane of Ca2+-loaded rat liver mitochondria. The MPTP opening was studied in the presence of bivalent metal ions (Sr2+, Ba2+, Mn2+, Co2+ and Ni2+), trivalent metal ions (Y3+ and La3+), and ruthenium red. We found that these metal ions (except Ba2+ and Co2+) as well as ruthenium red inhibited to the MPTP opening that manifested in preventing both diminution of the DNP-stimulated respiration and increase of the swelling and of the ΔΨmito dissipation in medium containing TlNO3, KNO3, and Ca2+. Inhibition of the MPTP opening by Sr2+ and Mn2+ is suggested because of their interaction with high affinity Ca2+ sites, facing the matrix side and participating in the MPTP opening. The inhibitory effects of metal ions (Y3+, La3+, and Ni2+), and ruthenium red are accordingly discussed in regard to competitive and noncompetitive inhibition of the mitochondrial Ca2+-uniporter. High concentrations (50μM) of Y3+ and La3+ favored of MPTP opening in the inner membrane of rat liver mitochondria in Ca2+ free medium containing TlNO3. The latter MPTP opening was markedly eliminated by MPTP inhibitors (cyclosporine A and ADP).
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      PubDate: 2014-09-01T01:45:57Z
       
  • Synthesis, DNA interaction and anticancer activity of copper(II) complexes
           
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Jie-Wen Liang , Yi Wang , Ke-Jie Du , Guan-Ying Li , Rui-Lin Guan , Liang-Nian Ji , Hui Chao
      Three novel copper(II) complexes CuL1Cl2 (1) (L1 =4′-(3-methoxyphenyl)-2,2′:6′- 2″-terpyridine), CuL2Cl2 (2) (L2 =4′-(4-methoxyphenyl)-2,2′:6′-2″-terpyridine) and CuL3Cl2 (3) (L3 =4′-(3,5-dimethoxyphenyl)-2,2′:6′-2″-terpyridine) have been synthesized and characterized. Absorption spectral titration experiments, ethidium bromide displacement assays, and cyclic voltammetric experiments were carried out and the results suggested that these complexes bound to DNA through an intercalative mode. Moreover, these complexes were found to cleave pBR322 DNA efficiently in the presence of glutathione (GSH), and exhibited good anticancer activity against HeLa, Hep-G2 and BEL-7402 cell lines. Nuclear chromatin cleavage was also observed by acridine orange/ethidium bromide (AO/EB) staining assays and comet assays. These results demonstrated that these three Cu(II) complexes caused DNA damage and induced the apoptosis of HeLa cells. Mechanistic investigations revealed the participation of reactive oxygen species which can be trapped by reactive oxygen species (ROS) radical scavengers and ROS sensors.
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      PubDate: 2014-09-01T01:45:57Z
       
  • New heteronuclear gold(I)–platinum(II) complexes with cytotoxic
           properties: Are two metals better than one?
    • Abstract: Publication date: December 2014
      Source:Journal of Inorganic Biochemistry, Volume 141
      Author(s): Margot Wenzel , Emilia Bigaeva , Philippe Richard , Pierre Le Gendre , Michel Picquet , Angela Casini , Ewen Bodio
      A series of mono- and heterodinuclear gold(I) and platinum(II) complexes with a new bipyridylamine-phosphine ligand have been synthesized and characterized. The X-ray structures of the ligand precursor 4-iodo-N,N-di(pyridin-2-yl)benzamide, and of one gold derivative are reported. All the complexes display antiproliferative properties in vitro in human cancer cells in the range of cisplatin or higher, which appear to correlate with compounds' uptake. Interestingly, studies of the interactions of the compounds with models of DNA indicate different mechanisms of actions with respect to cisplatin. The biological activity study of these complexes provides useful information about the interest of designing multimetallic complexes for enhanced cytotoxic properties.
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      PubDate: 2014-09-01T01:45:57Z
       
  • Cinnamaldehyde and cuminaldehyde thiosemicarbazones and their copper(II)
           
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Franco Bisceglie , Silvana Pinelli , Rossella Alinovi , Matteo Goldoni , Antonio Mutti , Alessandro Camerini , Lorenzo Piola , Pieralberto Tarasconi , Giorgio Pelosi
      This paper reports the synthesis and characterization of trans-cinnamaldehyde thiosemicarbazone (Htcin), cuminaldehyde thiosemicarbazone (Htcum) and their copper and nickel complexes. All the compounds, which on healthy cells (human fibroblasts) show a neglectable cytotoxicity, were screened in vitro in cell line U937 for their antileukemic activity. These compounds, in spite of their molecular similarity, present variegated behaviors. Htcin shows no inhibition activity in U935 cells, while both its metal complexes inhibit proliferation with IC50 at μM concentrations. The other ligand, Htcum, and its metal complexes, besides inhibiting proliferation, induce apoptosis. The cell cycle analysis highlights a G2/M checkpoint stop suggesting a possible direct action on DNA or on topoisomerase IIa. From CD and UV spectroscopy experiments, the DNA results to be not the main target of all these molecules, while both copper complexes are effective topoisomerase IIa inhibitors. All of these molecules activate caspase-9 and caspase-3, while caspase-8 activity is significantly induced by both cinnamaldehyde metal complexes. Tests on PgP and intracellular metal concentrations (determined by mean of atomic absorption spectrometry) show that the compounds tend to accumulate in the cytoplasm and that the cells do not manage to pump out copper and nickel ions.
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      PubDate: 2014-08-09T00:25:06Z
       
  • Copper-binding properties of the BIR2 and BIR3 domains of the X-linked
           inhibitor of apoptosis protein
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Yiwen Liang , Patrick M. Ewing , Willem J. Laursen , Valerie T. Tripp , Shubha Singh , Kathryn E. Splan
      The X-linked inhibitor of apoptosis protein (XIAP) is a zinc metalloprotein that has recently been implicated in copper homeostasis. XIAP mediates apoptosis via the inhibition of caspase enzymes through multiple baculovirus IAP repeat (BIR) domains, wherein zinc is coordinated by three cysteine amino acids and one histidine amino acid. XIAP binds copper ions directly at one or more unspecified sites, indicating that the protein may function as a copper sensor. We report the copper-binding properties of an XIAP construct containing the BIR2 and BIR3 domains. Absorption and emission spectroscopic measurements show that XIAP exhibits only a low-to-moderate affinity for Cu(II), but a strong affinity for Cu(I). Cu(I) is observed to bind at multiple sites within the BIR2 and BIR3 domains, including the CXXC motifs of the zinc structural sites and multiple BIR2 surface sites. Mutagenesis-based experiments reveal that surface cysteine residues mediate binding in the BIR2 domain and induce protein oligomerization under elevated copper concentrations. These results constitute the first spectroscopic evidence of copper–XIAP interactions.
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      PubDate: 2014-08-09T00:25:06Z
       
  • Synthesis, anticancer activity and toxicity of a water-soluble
           4S,5S-derivative of heptaplatin,
           
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Weiping Liu , Jing Jiang , Chengying Xie , Shuqian Hou , Haitian Quan , Qingsong Ye , Liguang Lou
      A water-soluble 4S,5S-derivative of heptaplatin, cis-{Pt(II)[(4S,5S)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]·(3-hydroxyl-cyclobutane-1,1-dicarboxylate)} was synthesized. The anticancer activity and toxicity were evaluated by comparing its interaction with DNA, cytotoxicity against four human cancer cell lines, antitumor efficiency in human gastric carcinoma NCI-N87 xenografts in nude mice, and preliminary side-effects in rats to those of its 4R,5R-optical isomer which is under preclinical development. Both isomers induce condensation of DNA to the same extent and have similar cytotoxicity, but show different antitumor activity and toxicity, probably owing to the difference in respective pharmacokinetic profiles. 4S,5S-Isomer seems to exhibit superior antitumor activity and less toxicity than 4R,5R-optical isomer as well as the parent heptaplatin. These results imply that 4S,5S-configuration as a new drug candidate may be better than 4R,5R-counterpart.
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      PubDate: 2014-08-09T00:25:06Z
       
  • Novel amphiphilic cationic porphyrin and its Ag(II) complex as potential
           anticancer agents
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Artak Tovmasyan , Nelli Babayan , David Poghosyan , Kristine Margaryan , Boris Harutyunyan , Rusanna Grigoryan , Natalia Sarkisyan , Ivan Spasojevic , Suren Mamyan , Lida Sahakyan , Rouben Aroutiounian , Robert Ghazaryan , Gennadi Gasparyan
      In the present study we have synthesized a novel amphiphilic porphyrin and its Ag(II) complex through modification of water-soluble porphyrinic structure in order to increase its lipophilicity and in turn pharmacological potency. New cationic non-symmetrical meso-substituted porphyrins were characterized by UV–visible, electrospray ionization mass spectrometry (ESI-MS), 1H NMR techniques, lipophilicity (thin-layer chromatographic retention factor, R f), and elemental analysis. The key toxicological profile (i.e. cytotoxicity and cell line- (cancer type-) specificity; genotoxicity; cell cycle effects) of amphiphilic Ag porphyrin was studied in human normal and cancer cell lines of various tissue origins and compared with its water-soluble analog. Structural modification of the molecule from water-soluble to amphiphilic resulted in a certain increase in the cytotoxicity and a decrease in cell line-specificity. Importantly, Ag(II) porphyrin showed less toxicity to normal cells and greater toxicity to their cancerous counterparts as compared to cisplatin. The amphiphilic complex was also not genotoxic and demonstrated a slight cytostatic effect via the cell cycle delay due to the prolongation of S-phase. As expected, the performed structural modification affected also the photocytotoxic activity of metal-free amphiphilic porphyrin. The ligand tested on cancer cell line revealed a dramatic (more than 70-fold) amplification of its phototoxic activity as compared to its water-soluble tetracationic metal-free analog. The compound combines low dark cytotoxicity with 5 fold stronger phototoxicity relative to Chlorin e6 and could be considered as a potential photosensitizer for further development in photodynamic therapy.
      Graphical abstract image

      PubDate: 2014-08-01T23:10:38Z
       
  • Evaluation of the Debye temperature for iron cores in human liver ferritin
           and its pharmaceutical analogue, Ferrum Lek, using Mössbauer
           spectroscopy
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): S.M. Dubiel , J. Cieślak , I.V. Alenkina , M.I. Oshtrakh , V.A. Semionkin
      An iron–polymaltose complex, Ferrum Lek, used as antianemic drug and considered as a ferritin analogue and human liver ferritin were investigated in the temperature range of 295–90K using 57Fe Mössbauer spectroscopy with a high velocity resolution (in 4096 channels). This study aimed to make a comparison of the Fe atom dynamics in the Ferrum Lek and ferritin iron cores by means of evaluation of the Debye temperature using the temperature dependence of the spectral center shift obtained with two different fitting procedures and the second order Doppler shift approach. The Debye temperature, evaluated as ΘD =502±24K for Ferrum Lek and ΘD =461±16K for human liver ferritin, demonstrated a very small difference in the Fe atom vibrations, reflecting a slightly smaller rigidity in the iron cores in human liver ferritin.
      Graphical abstract image

      PubDate: 2014-08-01T23:10:38Z
       
  • Cyclopalladated and cycloplatinated benzophenone imines: Antitumor,
           antibacterial and antioxidant activities, DNA interaction and cathepsin B
           inhibition
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Joan Albert , Lucía D'Andrea , Jaume Granell , Pepita Pla-Vilanova , Josefina Quirante , Muhammad Kaleem Khosa , Carme Calvis , Ramon Messeguer , Josefa Badía , Laura Baldomà , Mercè Font-Bardia , Teresa Calvet
      The antitumor, antibacterial and antioxidant activity, DNA interaction and cathepsin B inhibition of cyclo-ortho-palladated and -platinated compounds [Pd(C,N)]2(μ-X)2 [X=OAc (1), X=Cl (2)] and trans- N , P -[M(C,N)X(PPh3)] [M=Pd, X=OAc (3), M=Pd, X=Cl (4), M=Pt, X=Cl (5)] are discussed [(C,N)=cyclo-ortho-metallated benzophenone imine]. The cytotoxicity of compound 5 has been evaluated towards human breast (MDA-MB-231 and MCF-7) and colon (HCT-116) cancer cell lines and that of compounds 1–4 towards the HCT-116 human colon cancer cell line. These cytotoxicities have been compared with those previously reported for compounds 1–4 towards MDA-MB-231 and MCF-7 cancer cell lines. Compound 3 and 4 were approximately four times more active than cisplatin against the MDA-MB-231 and MCF-7 cancer cell lines, and compound 5, was approximately four times more potent than cisplatin against the HCT-116 cancer cell line. The antibacterial activity of compounds 1–5 was in between the ranges of activity of the commercial antibiotic compounds cefixime and roxithromycin. Complexes 1–2 and 4–5 presented also antioxidant activity. Compounds 1–5 alter the DNA tertiary structure in a similar way to cisplatin, but at higher concentration, and do not present a high efficiency as cathepsin B inhibitors. Compound 5 has not been previously described, and its preparation, characterization, and X-ray crystal structure are reported.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Antitumor platinum(IV) derivatives of oxaliplatin with axial valproato
           ligands
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Vojtech Novohradsky , Lenka Zerzankova , Jana Stepankova , Oldrich Vrana , Raji Raveendran , Dan Gibson , Jana Kasparkova , Viktor Brabec
      We report new anticancer prodrugs, platinum(IV) derivatives of oxaliplatin conjugated with valproic acid (VPA), a well-known drug having histone deacetylase inhibitory activity. Like most platinum(IV) derivatives, the cytotoxicity of the conjugates was lower in cell culture than that of oxaliplatin, but greater than those of its Pt(IV) derivative containing biologically inactive axial ligands in several cancer cell lines. Notably, these conjugates display activity in both cisplatin sensitive- and resistant tumor cells capable of both markedly enhanced accumulation in tumor cells and acting in a dual threat manner, concurrently targeting histone deacetylase and genomic DNA. These results demonstrate the dual targeting strategy to be a valuable route to pursue in the design of platinum agents which may be more effective in cancer types that are typically resistant to therapy by conventional cisplatin. Moreover, platinum(IV) derivatives containing VPA axial ligands seem to be promising dual-targeting candidates for additional preclinical studies.
      Graphical abstract image

      PubDate: 2014-07-27T22:37:22Z
       
  • Two structurally analogous ruthenium complexes as naked-eye and reversible
           molecular “light switch” for G-quadruplex DNA
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Xiao-Hui Lu , Shuo Shi , Jun-Liang Yao , Xing Gao , Hai-Liang Huang , Tian-Ming Yao
      A pair of symmetrical furyl based ruthenium(II) complexes ([Ru(phen)2dpq-df]2+ (1) and [Ru(bpy)2dpq-df]2+ (2) (phen=1,10-phenanthroline, bpy=2,2′-bipyridine, dpq-df=dipyrido (3,2-a:2′,3′-c) quinoxaline-difuran) have been prepared and characterized. The binding properties of both complexes toward G-quadruplex DNA have been investigated by fluorescence spectroscopy, UV–Vis spectroscopy, circular dichroism (CD), fluorescence resonance energy transfer (FRET) melting assays and molecular docking studies. The experimental results indicated that both Ru-complexes exhibited a remarkable “light switch” effect in the presence of hybrid G-quadruplex DNA. Interestingly, the “light switch” can be repeated off and on through the successive addition of Cu2+ ions and EDTA, and all these behaviors can be observed even by the naked eyes. Moreover, FRET melting assay revealed that both complexes could be potential stabilizers for G-quadruplex architectures. The computational studies not only confirmed that the two complex molecules bound to one G-quadruplex DNA molecule, but also explained the “light switch” effect.
      Graphical abstract image

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

      PubDate: 2014-07-27T22:37:22Z
       
  • Synthesis and properties of a new micellar
           polyphosphazene–platinum(II) conjugate drug
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Prakash G. Avaji , Hye In Joo , Jung Hyun Park , Kyung Su Park , Yong Joo Jun , Hwa Jeong Lee , Youn Soo Sohn
      Aiming at tumor targeting delivery of oxaliplatin using polymer therapy, a new monomeric platinum(II) complex (dach)Pt[HEDM] (dach: trans-(±)-1,2-diaminocyclohexane; HEDM: 2-hydroxyethoxydiethylmalate) was designed to include the antitumor moiety (dach)Pt and HEDM as a linker to the polyphosphazene backbone. This monomeric Pt-complex could easily be grafted to the PEGylated polyphosphazene backbone to prepare a novel polyphosphazene–Pt conjugate, [NP(MPEG550)(dach)Pt(EM)]n [MPEG550: methoxy poly(ethylene glycol) with an average molecular weight of 550; EM: ethoxymalate]. This amphiphilic polyphosphazene–Pt conjugate was found to self-assemble into stable polymeric micelles of a mean diameter of 130nm, which is suitable for passive tumor targeting by enhanced permeability and retention (EPR) effect. Pharmacokinetic study of this polymer conjugate exhibited long blood circulation as expected and longer half-life (t1/2β=9.52h) compared with oxaliplatin (3.47h), and much larger AUC (area under the curve) value (25,831ng·h/mL) compared with oxaliplatin (1194ng·h/mL). Biodistribution study of the polymer conjugate has shown excellent tumor selectivity with the tumor to tissue ratio of 3.84 at 2h post injection and 11.7 at 24h post injection probably due to the EPR effect of the polymer conjugate while no tumor selectivity was observed for monomeric oxaliplatin. Furthermore, accumulation of this polymer conjugate in kidney was much lower compared with oxaliplatin. Also the nude mouse xenograft trial of the polymer conjugate has shown higher antitumor efficacy compared with oxaliplatin.
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      PubDate: 2014-07-27T22:37:22Z
       
  • Cellular uptake and cytotoxicity of a near-IR fluorescent
           corrole–TiO2 nanoconjugate
    • Abstract: Publication date: November 2014
      Source:Journal of Inorganic Biochemistry, Volume 140
      Author(s): Carl M. Blumenfeld , Bryce F. Sadtler , G. Esteban Fernandez , Lily Dara , Cathie Nguyen , Felix Alonso-Valenteen , Lali Medina-Kauwe , Rex A. Moats , Nathan S. Lewis , Robert H. Grubbs , Harry B. Gray , Karn Sorasaenee
      We are investigating the biological and biomedical imaging roles and impacts of fluorescent metallocorrole–TiO2 nanoconjugates as potential near-infrared optical contrast agents in vitro in cancer and normal cell lines. The TiO2 nanoconjugate labeled with the small molecule 2,17-bis(chlorosulfonyl)-5,10,15-tris(pentafluorophenyl)corrolato aluminum(III) (1-Al–TiO2) was prepared. The nanoparticle 1-Al–TiO2 was characterized by transmission electron microscopy (TEM) and integrating-sphere electronic absorption spectroscopy. TEM images of three different samples of TiO2 nanoparticles (bare, H2O2 etched, and 1-Al functionalized) showed similarity in shapes and sizes with an average diameter of 29nm for 1-Al–TiO2. Loading of 1-Al on the TiO2 surfaces was determined to be ca. 20–40mg 1-Al/g TiO2. Confocal fluorescence microscopy (CFM) studies of luciferase-transfected primary human glioblastoma U87-Luc cells treated with the nanoconjugate 1-Al–TiO2 as the contrast agent in various concentrations were performed. The CFM images revealed that 1-Al–TiO2 was found inside the cancer cells even at low doses (0.02–2μg/mL) and localized in the cytosol. Bioluminescence studies of the U87-Luc cells exposed to various amounts of 1-Al–TiO2 showed minimal cytotoxic effects even at higher doses (2–2000μg/mL) after 24h. A similar observation was made using primary mouse hepatocytes (PMH) treated with 1-Al–TiO2 at low doses (0.0003–3μg/mL). Longer incubation times (after 48 and 72h for U87-Luc) and higher doses (>20μg/mL 1-Al–TiO2 for U87-Luc and >3μg/mL 1-Al–TiO2 for PMH) showed decreased cell viability.
      Graphical abstract image

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

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

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

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

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

      PubDate: 2014-07-27T22:37:22Z
       
 
 
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