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  Subjects -> CHEMISTRY (Total: 843 journals)
    - ANALYTICAL CHEMISTRY (47 journals)
    - CHEMISTRY (594 journals)
    - CRYSTALLOGRAPHY (22 journals)
    - ELECTROCHEMISTRY (26 journals)
    - INORGANIC CHEMISTRY (42 journals)
    - ORGANIC CHEMISTRY (45 journals)
    - PHYSICAL CHEMISTRY (67 journals)

INORGANIC CHEMISTRY (42 journals)

Acta Polymerica     Hybrid Journal   (Followers: 7)
Additives for Polymers     Full-text available via subscription   (Followers: 20)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 6)
Advances in Polymer Technology     Hybrid Journal   (Followers: 11)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 3)
Bioinorganic Chemistry and Applications     Open Access   (Followers: 6)
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: 1)
European Journal of Inorganic Chemistry     Hybrid Journal   (Followers: 8)
European Polymer Journal     Hybrid Journal   (Followers: 44)
Heterocyclic Communications     Hybrid Journal   (Followers: 1)
High Performance Polymers     Hybrid Journal  
Indian Journal of Chemistry - Section A     Open Access   (Followers: 7)
Inorganic Chemistry     Full-text available via subscription   (Followers: 24)
Inorganic Chemistry Communications     Hybrid Journal   (Followers: 9)
Inorganic Chemistry Frontiers     Full-text available via subscription   (Followers: 1)
Inorganic Materials     Hybrid Journal   (Followers: 3)
Inorganic Materials: Applied Research     Hybrid Journal   (Followers: 1)
Inorganica Chimica Acta     Hybrid Journal   (Followers: 5)
Inorganics     Open Access  
International Journal of Bio-Inorganic Hybrid Nanomaterials     Open Access  
International Journal of Inorganic Chemistry     Open Access   (Followers: 1)
JBIC Journal of Biological Inorganic Chemistry     Hybrid Journal   (Followers: 4)
Journal of Inorganic and Organometallic Polymers and Materials     Partially Free   (Followers: 7)
Journal of Inorganic Biochemistry     Hybrid Journal   (Followers: 2)
Journal of Inorganic Chemistry     Open Access   (Followers: 3)
Journal of Polymer Engineering     Hybrid Journal   (Followers: 9)
Journal of Polymers and the Environment     Hybrid Journal   (Followers: 3)
Journal of Separation Science     Hybrid Journal   (Followers: 10)
Metallodrugs     Open Access   (Followers: 1)
Open Journal of Inorganic Chemistry     Open Access   (Followers: 3)
Plasmas and Polymers     Hybrid Journal  
Polymer Bulletin     Hybrid Journal   (Followers: 7)
Polymer Composites     Hybrid Journal   (Followers: 11)
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: 1)
Zeitschrift für Kristallographie - New Crystal Structures     Open Access  
Journal Cover Journal of Inorganic Biochemistry
  [SJR: 0.96]   [H-I: 87]   [2 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0162-0134
   Published by Elsevier Homepage  [2801 journals]
  • Azido- and chlorido-cobalt complex as carrier-prototypes for antitumoral
           prodrugs
    • Abstract: Publication date: Available online 27 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Bianca M. Pires, Letícia C. Giacomin, Frederico A.V. Castro, Amanda dos S. Cavalcanti, Marcos D. Pereira, Adailton J. Bortoluzzi, Roberto B. Faria, Marciela Scarpellini
      Cobalt(III) complexes are well-suited systems for cytotoxic drug release under hypoxic conditions. Here, we investigate the effect of cytotoxic azide release by cobalt- containing carrier-prototypes for antitumoral prodrugs. In addition, we study the species formed after reduction of Co3+ →Co2+ in the proposed models for these prodrugs. The three new complexes, [CoIII(L)(N3)2]BF4 (1), [{CoII(L)(N3)}2](ClO4)2 (2), and [CoII(L)Cl]PF6 (3), L=[(bis(1-methylimidazol-2-yl)methyl)(2-(pyridyl-2-yl)ethyl)amine], were synthesized and studied by several spectroscopic, spectrometric, electrochemical, and crystallographic methods. Reactivity spectroscopic data reveal that complex 1 is able to release N3 − either after reduction with ascorbic acid, or by ambient light irradiation, in aqueous phosphate buffer (pH6.2, 7.0 and 7.4) and acetonitrile solutions. The antitumoral activity of compounds 1–3 were tested in normoxia on MCF-7 (human breast adenocarcinoma), PC-3 (human prostate) and A-549 (human lung adenocarcinoma epithelial) cell lines, after 24h of exposure. Either complexes or NaN3 presented IC50 values higher than 200μM, showing lower cytotoxicity than the clinical standard antitumoral complex cisplatin, in the same conditions. Complexes 1–3 were also evaluated in hypoxia on A-549 and results indicate high IC50 data (>200μM) after 24h of exposure. However, an increase of cancer cell susceptibility to 1 and 2 was observed at 300μM. Regarding to complex 3, no cytotoxic activity was observed in the same conditions. Data presented here indicate that the tridentate ligand L is able to stabilize both oxidation states of cobalt (+3 and +2). In addition, the cobalt(III) complex yield low cytotoxic cobalt(II) species after reduction, which corroborates to their proposition as carrier prototypes for antitumoral prodrugs.
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      PubDate: 2016-01-29T01:59:15Z
       
  • Preparation, optical and electrochemical properties, and molecular orbital
           calculations of tetraazaporphyrinato ruthenium (II) bis(4-methylpyridine)
           fused with one to four diphenylthiophene units
    • Abstract: Publication date: Available online 28 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Takeshi Kimura, Naoko Murakami, Eiichi Suzuki, Taniyuki Furuyama, Tsukasa Nakahodo, Hisashi Fujihara, Nagao Kobayashi
      2,5-Diphenyl-3,4-dicyanothiophene (1) and phthalonitrile (2) were mixed and treated with ruthenium (III) trichloride, 4-methylpyridine, and DBU in 2-ethoxyethanol at 135°C, to produce low-symmetrical tetraazaporphyrins (TAPs) (3), (4), (5), and (6) with one to three thiophene rings. Two thiophene-annelated tetraazaporphyrins were isolated as opposite and adjacent isomers 4 and 5. The structure of 3 was determined by X-ray crystallography, showing that the thiophene ring linked at the 3,4-positions on the tetraazaporphyrin scaffold deviates from the mean plane of the four central pyrrole nitrogen atoms (N1–N3–N5–N7). Optical and electrochemical properties of the products were examined by UV–vis and magnetic circular dichroism (MCD) spectroscopy, together with cyclic voltammetry. In the 1H NMR spectra, the signals of 4-methylpyridine coordinating to the central ruthenium atom appeared at a higher magnetic field than those of uncoordinated 4-methylpyridine itself due to the shielding effect of the TAP ring. Increasing the number of fused thiophene rings resulted in 1) lower magnetic field shifts of the signals of axially coordinated 4-methylpyridine in the 1H NMR spectra, 2) lower energy shifts of the Q band absorption in the UV–vis spectra, and 3) decreasing (cathodic shift) of the first oxidation potentials. The structures of simplified model compounds were optimized using the DFT method with the Gaussian 09 program at the B3LYP/LANL2DZ level for the Ru atom and the B3LYP/6-31G (d, p) level for the C, H, N, and S atoms. The optimized structures were utilized to calculate the NMR shielding constants, the HOMO and LUMO orbital energies, and the electronic absorption spectra.
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      PubDate: 2016-01-29T01:59:15Z
       
  • The structures, cytotoxicity, apoptosis and molecular docking controlled
           by the aliphatic chain of palladium(II) complexes
    • Abstract: Publication date: Available online 21 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): MingChang Zhu, Xiaoting Cui, Shaozhong Zhang, Lei Liu, ZhengBo Han, EnJun Gao
      A new series of Pd(II) complexes derived from benzenealkyl dicarboxylate ligands, [Pd(Ln)(phen)] (phen=2,9-dimethyl-1,10-phenanthroline, complex 1: L 1 =phenylmalonate; complex 2: L 2 =benzylmalonate; complex 3: L 3 =(2-phenylethyl)malonate; complex 4: L 4 =(3-phenylpropyl)malonate) have been synthesized under room temperature condition. These complexes contain a long dicarboxylate aliphatic chain. They were characterized by elemental analysis, infrared spectroscopy, single crystal X-ray diffraction. The binding of complexes with fish sperm DNA (FS-DNA) was investigated by UV absorption and fluorescence spectra. Gel electrophoresis assay demonstrated the ability of the complexes to cleave the pBR322 plasmid DNA. The cytotoxic activity of the complexes was tested against two different cancer cell lines, HeLa and HL-60. Cytotoxic activity studies showed the four complexes exhibited significant cancer cell inhibitory rate. Further flow cytometry experiments showed that the cytotoxic Pd(II) complexes induced apoptosis of HL-60 tumour cell lines. The molecular dynamic simulations and docking methods were used to predict the DNA binding affinity of Pd(II) complexes by the resulting relative binding energy of complexes with DNA -6.01, −6.25, −7.24 and −7.59kcal/mol, while with DNA-Topoisomerase I(Topo I) -7.98, −9.25, −10.2 and −11.5kcal/mol, respectively. The good visualisation images supported with the experimental results of structure–activity relationship between cytotoxicity and carbon chain length.
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      PubDate: 2016-01-23T01:51:42Z
       
  • Complexation and molecular modeling studies of europium(III)-Gallic
           acid-amino acid complexes
    • Abstract: Publication date: Available online 21 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Mohamed Taha, Imran Khan, João A.P. Coutinho
      With many metal-based drugs extensively used today in the treatment of cancer, attention has focused on the development of new coordination compounds with antitumor activity with europium (III) complexes recently introduced as novel anticancer drugs. The aim of this work is to design new Eu(III) complexes with gallic acid, an antioxidant phenolic compound. Gallic acid was chosen because it shows anticancer activity without harming health cells. As antioxidant, it helps to protect human cells against oxidative damage that implicated in DNA damage, cancer, and accelerated cell aging. In this work, the formation of binary and ternary complexes of Eu(III) with gallic acid, primary ligand, and amino acids alanine, leucine, isoleucine, and tryptophan were studied by glass electrode potentiometry in aqueous solution containing 0.1 M NaNO3 at (298.2 ± 0.1) K. Their overall stability constants were evaluated and the concentration distributions of the complexes species in solution were calculated. The protonation constants of gallic acid and amino acids were also determined at our experimental conditions and compared with those predicted by using conductor-like screening model for realistic solvation (COSMO-RS) model. The geometries of Eu(III)-gallic acid complexes were characterized by the density functional theory (DFT). The spectroscopic UV–visible and photoluminescence measurements are carried out to confirm the formation of Eu(III)-gallic acid complexes in aqueous solutions.
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      PubDate: 2016-01-23T01:51:42Z
       
  • Observation of the seleno bis-(S-glutathionyl) arsinium anion in rat bile
    • Abstract: Publication date: Available online 21 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Graham N. George, Jürgen Gailer, Olena Ponomarenko, Paul F. La Porte, Karen Strait, Mohammad Alauddin, Habibul Ahsan, Selim Ahmed, Julian Spallholz, Ingrid J. Pickering
      Certain arsenic and selenium compounds show a remarkable mutual cancellation of toxicities, where a lethal dose of one can be voided by an equimolar and otherwise lethal dose of the other. It is now well established that the molecular basis of this antagonism is the formation and biliary excretion of seleno bis-(S-glutathionyl) arsinium anion [(GS)2AsSe]−. Previous work has definitively demonstrated the presence of [(GS)2AsSe]− in rabbit bile, but only in the presence of other arsenic and selenium species. Rabbits have a gall bladder, which concentrates bile and lowers its pH; it seems likely that this may be responsible for the breakdown of biliary [(GS)2AsSe]−. Since rats have no gall bladder, the bile proceeds directly through the bile duct from the hepatobiliary tree. In the present work we have shown that the primary product of biliary co-excretion of arsenic and selenium in rats is [(GS)2AsSe]−, with essentially 100% of the arsenic and selenium present as this species. The chemical plausibility of the XAS-derived structural conclusions of this novel arsenic and selenium co-excretion product are supported by density functional theory calculations. These results establish the biomolecular basis to further explore the use of selenium dietary supplements as a possible palliative for chronic low-level arsenic poisoning of human populations.
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      PubDate: 2016-01-23T01:51:42Z
       
  • Apomaghemite as a doxorubicin carrier for anticancer drug delivery
    • Abstract: Publication date: Available online 21 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Rocío Jurado, Paulina Frączek, Mélissa Droetto, Purificación Sánchez, Elsa Valero, José M. Domínguez-Vera, Natividad Gálvez
      Protein cages have well-defined structures and can be chemically and biologically engineered in many ways, making them useful platforms for drug delivery applications. Taking advantage of the unique structure feature of apoferritin, a new theranostic nanocarrier is proposed herein. The apoferritin protein is effective for the encapsulation of maghemite nanoparticles and for loading a significant dose of doxorubicin (DOX) drug. This simultaneous loading of maghemite nanoparticles and DOX has been achieved either using co-encapsulation or surface-binding approaches. Maghemite nanoparticles coated with the protein apoferritin, are an effective long-term MRI liver contrast agent and we report here that additionally can serve as an anticancer drug-delivery system. In particular we show that maghemite-containing apoferritin can sustain the DOX delivery under period of 10 to 25days depending on the environmental conditions.
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      PubDate: 2016-01-23T01:51:42Z
       
  • Catalytic reduction of dioxygen with modified Thermus thermophilus
           cytochrome c552
    • Abstract: Publication date: Available online 20 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Jonathan Husband, Michael S. Aaron, Rajneesh K. Bains, Andrew R. Lewis, Jeffrey J. Warren
      Efficient catalysis of the oxygen reduction reaction (ORR) is of central importance to function in fuel cells. Metalloproteins, such as laccase (Cu) or cytochrome c oxidase (Cu/Fe-heme) carry out the 4H+/4e− reduction quite efficiently, but using large, complex protein frameworks. Smaller heme proteins also can carry out ORR, but less efficiently. To gain greater insight into features that promote efficient ORR, we expressed, characterized, and investigated the electrochemical behavior of six new mutants of cytochrome c 552 from T. thermophilus: V49S/M69A, V49T/M69A, L29D/V49S/M69A, P27A/P28A/L29D/V49S/M69A, and P27A/P28A/L29D/V49T/M69A. Mutation to V49 causes only minor shifts to FeIII/II reduction potentials (E°´), but introduction of Ser provides a hydrogen bond donor that slightly enhances oxygen reduction activity. Mutation of L29 to D induces small shifts in heme optical spectra, but not to E°´ (within experimental error). Replacement of P27 and P28 with A in both positions induces a−50mV shift in E°´, again with small changes to the optical spectra. Both the optical spectra and reduction potentials have signatures consistent with peroxidase enzymes. The V49S and V49T mutations have the largest impact of ORR catalysis, suggesting that increased electron density at the Fe site does not improve O2 reduction chemistry.
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      PubDate: 2016-01-23T01:51:42Z
       
  • Synthesis, characterization, in vitro cytotoxicity and anticancer effects
           of ruthenium(II) complexes on BEL-7402 cells
    • Abstract: Publication date: Available online 22 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Cheng Zhang, Bing-Jie Han, Chuan-Chuan Zeng, Shang-Hai Lai, Wei Li, Bing Tang, Dan Wan, Guang-Bin Jiang, Yun-Jun Liu
      Four new ruthenium(II) polypyridyl complexes [Ru(dmb)2(DQTT)](ClO4)2 (1) (DQTT =12-(1,4-dihydroquinoxalin-6-yl)-4,5,9,14-tetraazabenzo[b]triphenylene, dmb=4,4′-dimethyl-2,2′-bipyridine), [Ru(bpy)2(DQTT)](ClO4)2 (2) (bpy=2,2′-bipyridine), [Ru(phen)2(DQTT)](ClO4)2 (3) (phen =1,10-phenanthroline) and [Ru(dmp)2(DQTT)](ClO4)2 (4) (dmp=2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized by elemental analysis, ESI-MS, 1H NMR and 13C NMR. The cytotoxic activity in vitro of the complexes was evaluated against human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines by MTT (3-(4,5-dimethylthiazole)-2,5-diphenyltetraazolium bromide) method. The IC50 values of complexes 1–4 against BEL-7402 cells are 31.8±1.0, 35.8±1.6, 29.0±0.8 and 25.0±0.9μM, respectively. The morphological apoptosis was investigated with AO/EB (acridine orange/ethidium bromide) and Hoechst 33,258 staining methods. The DNA damage was assayed by comet assay. The inhibition of cell migration was evaluated by the wound healing assay. The levels of ROS (reactive oxygen species) and the changes of mitochondrial membrane potential were studied under fluorescent microscope. The percentages in the cells of apoptotic and necrotic cells and the cell cycle arrest were determined by flow cytometry. The expression of Bcl-2 family proteins was investigated by western blot analysis. The results show that the complexes induce BEL-7402 cells apoptosis through a ROS-mediated mitochondrial dysfunction pathway, which was accompanied by regulation of the expression of Bcl-2 family proteins.
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      PubDate: 2016-01-23T01:51:42Z
       
  • Adsorption of the cis-[Pt(NH3)2(P2O7)]2− (phosphaplatin) on
           hydroxyapatite nanocrystals as a smart way to selectively release
           activated cis-[Pt(NH3)2Cl2] (cisplatin) in tumor tissues
    • Abstract: Publication date: Available online 20 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Michele Benedetti, Federica De Castro, Alessandro Romano, Danilo Migoni, Barbara Piccinni, Tiziano Verri, Marco Lelli, Norberto Roveri, Francesco P. Fanizzi
      The relevant adsorption of cis-[Pt(NH3)2(P2O7)]2− (phosphaplatin) on hydroxyapatite nanocrystals (nHAP) was observed and studied in water suspension. Phosphaplatin cytotoxicity, which is very low for HeLa, MCF-7 and HS-5 cell lines could be enhanced, reaching that of cisplatin, by interaction with solid nHAP. This effect stems from nHAP ability to catalyze the phosphaplatin hydrolysis, producing the same hydrolytic species responsible for cisplatin antitumor activity.
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      PubDate: 2016-01-23T01:51:42Z
       
  • Bovine serum albumin binding, antioxidant and anticancer properties of an
           oxidovanadium(IV) complex with luteolin
    • Abstract: Publication date: Available online 22 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Luciana G. Naso, Luis Lezama, María Valcarcel, Clarisa Salado, Patricia Villacé, Danel Kortazar, Evelina G. Ferrer, Patricia A.M. Williams
      Chemotherapy using metal coordination compounds for cancer treatment is the work of ongoing research. Continuing our research on the improvement of the anticancer activity of natural flavonoids by metal complexation, a coordination compound of the natural antioxidant flavone luteolin (lut) and the oxidovanadium(IV) cation has been synthesized and characterized. Using different physicochemical measurements some structural aspects of [VO(lut)(H2O)2]Na.3H2O (VOlut) were determined. The metal coordinated to two cis-deprotonated oxygen atoms (ArO−) of the ligand and two H2O molecules. Magnetic measurements in solid state indicated the presence of an effective exchange pathway between adjacent vanadium ions. VOlut improved the antioxidant capacity of luteolin only against hydroxyl radical. The antitumoral effects were evaluated on MDAMB231 breast cancer and A549 lung cancer cell lines. VOlut exhibited higher viability inhibition (IC50 =17μM) than the ligand on MDAMB231 cells but they have the same behavior on A549 cells (ca. IC50 =60μM). At least oxidative stress processes were active during cancer cell-killing. When metals chelated through the carbonyl group and one adjacent OH group of the flavonoid an effective improvement of the biological properties has been observed. In VOlut the different coordination may be the cause of the small improvement of some of the tested properties of the flavonoid. Luteolin and VOlut could be distributed and transported in vivo. Luteolin interacted in the microenvironment of the tryptophan group of the serum binding protein, BSA, by means of electrostatic forces and its complex bind the protein by H bonding and van der Waals interactions.
      Graphical abstract image

      PubDate: 2016-01-23T01:51:42Z
       
  • Potentiation of mitochondrial dysfunction in tumor cells by conjugates of
           metabolic modulator dichloroacetate with a Pt(IV) derivative of
           oxaliplatin
    • Abstract: Publication date: March 2016
      Source:Journal of Inorganic Biochemistry, Volume 156
      Author(s): Juraj Zajac, Hana Kostrhunova, Vojtech Novohradsky, Oldrich Vrana, Raji Raveendran, Dan Gibson, Jana Kasparkova, Viktor Brabec
      The molecular and cellular mechanisms of enhanced toxic effects in tumor cells of the Pt(IV) derivatives of antitumor oxaliplatin containing axial dichloroacetate (DCA) ligands were investigated. DCA ligands were chosen because DCA has shown great potential as an apoptosis sensitizer and anticancer agent reverting the Wartburg effect. In addition, DCA reverses mitochondrial changes in a wide range of cancers, promoting tumor cell apoptosis in a mitochondrial-dependent pathway. We demonstrate that (i) the transformation of oxaliplatin to its Pt(IV) derivatives containing axial DCA ligands markedly enhances toxicity in cancer cells and helps overcome inherent and acquired resistance to cisplatin and oxaliplatin; (ii) a significant fraction of the intact molecules of DCA conjugates with Pt(IV) derivative of oxaliplatin accumulates in cancer cells where it releases free DCA; (iii) mechanism of biological action of the Pt(IV) derivatives of oxaliplatin containing DCA ligands is connected with the effects of DCA released in cancer cells from the Pt(IV) prodrugs on mitochondria and metabolism of glucose; (iv) treatments with the Pt(IV) derivatives of oxaliplatin containing DCA ligands activate an autophagic response in human colorectal cancer cells; (v) the toxic effects in cancer cells of the Pt(IV) derivatives of oxaliplatin containing DCA ligands can be potentiated if cells are treated with these prodrugs in combination with 5-fluorouracil. These properties of the Pt(IV) derivatives of oxaliplatin containing DCA ligands provide opportunities for further development of new platinum-based agents with the capability of killing cancer cells resistant to conventional antitumor platinum drugs used in the clinic.
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      PubDate: 2016-01-19T02:43:06Z
       
  • Structural and functional effects of benzimidazole/thioether–copper
           complexes with antitumor activity on cell membranes and molecular models
    • Abstract: Publication date: March 2016
      Source:Journal of Inorganic Biochemistry, Volume 156
      Author(s): Ivan Castillo, Mario Suwalsky, María José Gallardo, Valentina Troncoso, Brenda N. Sánchez-Eguía, Edelmiro Santiago-Osorio, Itzen Aguiñiga, Ana K. González-Ugarte
      Two cytotoxic copper(II) complexes with N–H and N-methylated benzimidazole-derived ligands (Cu-L 2 and Cu-L 2Me ) were synthesized and made to interact with human erythrocytes and molecular models of their plasmatic membranes. The latter consisted in lipid bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), lipids of the types present in the outer and inner monolayers of the human erythrocyte membrane, respectively. Initial assessment of the interaction of the complexes with DMPC and DMPE consisted of X-ray diffraction studies, which showed preferential interactions with the former. Scanning electron microscopy (SEM) of erythrocytes incubated with solutions of the Cu(II) complexes evidenced deformation of the cells to stomatocytes and knizocytes by Cu-L 2 and Cu-L 2Me due to interactions with the inner and outer leaflets of the cell membranes, respectively. This was further confirmed by real-time observation of the dose-dependent effects of the complexes on live erythrocytes by defocusing microscopy (DM). The combined observations, including the increased antiproliferative activity of the N-methylated complex Cu-L 2Me over that of Cu-L 2 is rationalized based on the higher lipophilicity of the former. This property would facilitate passive diffusion of Cu-L 2Me through the cell membrane, particularly in the initial stages when the DMPC-rich outer leaflet is involved. In contrast, the benzimidazole N–H groups of Cu-L 2 may participate in hydrogen bonding with DMPE polar groups; this result is consistent with the formation of stomatocyte induced by the latter complex.
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      PubDate: 2016-01-19T02:43:06Z
       
  • Group 11 complexes with amino acid derivatives: Synthesis and antitumoral
           studies
    • Abstract: Publication date: March 2016
      Source:Journal of Inorganic Biochemistry, Volume 156
      Author(s): Lourdes Ortego, Margarida Meireles, Cornelia Kasper, Antonio Laguna, M. Dolores Villacampa, M. Concepción Gimeno
      Gold(I), gold(III), silver(I) and copper(I) complexes with modified amino acid esters and phosphine ligands have been prepared in order to test their cytotoxic activity. Two different phosphine fragments, PPh3 and PPh2py (py=pyridine), have been used. The amino acid esters have been modified by introducing an aromatic amine as pyridine that coordinates metal fragments through the nitrogen atom, giving complexes of the type [M(L)(PR3)]+ or [AuCl3(L)] (L= l-valine-N-(4-pyridylcarbonyl) methyl ester (L1), l-alanine-N-(4-pyridylcarbonyl) methyl ester (L2), l-phenylalanine-N-(4-pyridylcarbonyl) methyl-ester) (L3); M=Au(I), Ag(I), Cu(I), PR3 =PPh3, PPh2py). The in vitro cytotoxic activity of metal complexes was tested against four tumor human cell lines and one tumor mouse cell line. A metabolic activity test (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTT) was used and IC50 values were compared with those obtained for cisplatin. Several complexes displayed significant cytotoxic activities. In order to determine whether antiproliferation and cell death are associated with apoptosis, NIH-3T3 cells were exposed to five selected complexes (Annexin V+ FITC, PI) and analyzed by flow cytometry. These experiments showed that the mechanism by which the complexes inhibit cell proliferation inducing cell death in NIH-3T3 cells is mainly apoptotic.
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      PubDate: 2016-01-19T02:43:06Z
       
  • Toward a better understanding of the oxaliplatin mode of action upon the
           steric hindrance of 1,2-diaminocyclohexane and its analogue
    • Abstract: Publication date: Available online 15 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Zhimei Wang, Mian Wu, Shaohua Gou
      The present research is concerned with the mechanism investigation on the interaction between oxaliplatin and guanosine 5′-monophosphate (GMP) in the presence of glutathione (GSH). The binding modes of oxaliplatin with GMP and GSH were explored by HPLC and LC–MS techniques, respectively, in which four key intermediates were found and five adducts were determined in the reaction. The results indicated that GSH can interfere with the reaction between oxaliplatin and DNA in two ways. One is by competing with GMP to bind the active platinum unit, and the other is by substituting the guanine-N7 atom of DNA to form inactive platinum species. In contrast to oxaliplatin with trans 1,2-diaminocyclohexane as spatial framework, a known platinum(II) complex, characteristic of trans-bicyclo[2.2.2]octane-7,8-diamine possessing dicyclic steric hindrance, was also studied in the same way to explicit its mode of action with DNA.
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      PubDate: 2016-01-19T02:43:06Z
       
  • γ-cyclodextrin capped silver nanoparticles for molecular recognition
           and enhancement of antibacterial activity of chloramphenicol
    • Abstract: Publication date: Available online 11 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Ramesh Gannimani, Muthusamy Ramesh, Sphamandla Mtambo, Karen Pillay, Mahmoud E. Soliman, Patrick Govender
      Computational studies were conducted to identify the favourable formation of the inclusion complex of chloramphenicol with cyclodextrins. The results of molecular docking and molecular dynamics predicted the strongest interaction of chloramphenicol with γ-cyclodextrin. Further, the inclusion complex of chloramphenicol with γ-cyclodextrin was experimentally prepared and a phenomenon of inclusion was verified by using different characterization techniques such as thermogravimetric analysis, differential scanning calorimetry, 1H nuclear magnetic resonance (NMR) and two dimensional nuclear overhauser effect spectroscopy (NOESY) experiments. From these results it was concluded that γ-cyclodextrins could be an appropriate cyclodextrin polymer which can be used to functionalize chloramphenicol on the surface of silver nanoparticles. In addition, γ-cyclodextrin capped silver nanoparticles were synthesized and characterized using UV–visible spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray analysis (EDX), Fourier transform infrared spectroscopy (FTIR) and zeta potential analysis. Molecular recognition of chloramphenicol by these cylcodextrin capped silver nanoparticles was confirmed by surface enhanced raman spectroscopy (SERS) experiments. Synergistic antibacterial effect of chloramphenicol with γ-cyclodextrin capped silver nanoparticles was evaluated against Pseudomonas aeruginosa (ATCC 27853), Enterococcus faecalis (ATCC 5129), Klebsiella pneumoniae (ATCC 700603) and Staphylococcus aureus (ATCC 43300). The results from the antibacterial experiment were favourable thus allowing us to conclude that the approach of modifying organic drug molecules with cyclodextrin capped inorganic silver nanoparticles could help to enhance the antibacterial activity of them.
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      PubDate: 2016-01-15T10:07:52Z
       
  • The chemical biology of Cu(II) complexes with imidazole or thiazole
           containing ligands: Synthesis, crystal structures and comparative
           biological activity
    • Abstract: Publication date: Available online 11 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Adam Lewis, Molly McDonald, Stephanie Scharbach, Stefan Hamaway, Melissa Plooster, Kyle Peters, Kristin M. Fox, Lynne Cassimeris, Joseph M. Tanski, Laurie A. Tyler
      The synthesis and characterization of two copper(II) complexes containing 2-(2-pyridyl)benzimidazole (PyBIm) are reported with the biological activity of these two complexes and a third Cu(II) complex containing 2-(2-pyridyl)benzothiazole (PyBTh). Complex 1, [Cu(PyBIm)(NO3)(H2O)](NO3), is a four coordinate, distorted square planar species with one ligand (N,N), nitrate and water bound to Cu(II). The [Cu(PyBIm)3](BF4)2 complex (2) has distorted octahedral geometry with a 3:1 Py(BIm) ligand to metal ratio. The distorted trigonal bi-pyramidal geometry of compound 3, [Cu(PyBTh)2(H2O)](BF4)2, is comprised of two PyBTh ligands and one water. Biological activity of 1–3 has been assessed by analyzing DNA interaction, nuclease ability, cytotoxic activity and antibacterial Properties. c omplex 3 exhibits potent concentration dependent SC-DNA cleavage forming single- and double-nicked DNA in contrast to the weak activity of complexes 1 and 2. Mechanistic studies indicate all complexes utilize an oxidative mechanism however 1 and 2 employ O2 − as the principal reactive oxygen species while the highly active 3 utilizes 1O2. The interaction between 1 and 3 and DNA was investigated using fluorescence emission spectroscopy and revealed all complexes strongly intercalate DNA with Kapp values of 2.65 x 106, 1.85 x 106 and 2.72 x 106 M−1, respectively. Cytotoxic effects of 1–3 were examined using HeLa and K562 cells and show cell death in the micromolar range with the activity of 1 ≈ 2 and were slightly higher than 3. Similar reactivity was observed in the antibacterial studies with E. coli and S. aureus. A detailed comparative analysis of the three complexes is presented.
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      PubDate: 2016-01-15T10:07:52Z
       
  • One-dimensional chiral copper (II) complexes with novel Nano-structures
           and superior antitumor activity
    • Abstract: Publication date: Available online 11 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Wei Chuan Zhang, Xue Tang, Xiaoming Lu
      Three novel copper(II) compounds of formulas {[Cu(Phen)(Ala)]·NO3·H2O}n (1), {[Cu(Phen)(Ala)]·NO3}n (2) and [Cu(Ala)2]n (3) have been synthesized and determined by X-ray diffraction. 1 and 2 are shown in one dimensional long-chain chiral structures, and 3 is a two dimensional checkerboard-type structure. Both 1 and 2 displayed a higher anticancer activity than 3 against various cancer cells, even higher than the similar mononuclear complexes and clinical anticancer drug 5-fluorouracil. The noncancerous cell lines (CCC-HEL-1) have showed that complexes 1–3 have hardly any cytotoxicity. Transmission electron microscopy was studied to show the nano-structure and π function of two complexes. The ligand 1,10-phenanthroline inserted into its enantiomer lead complex 1 stable, and the π–π interaction outside the chain made complex 2 active, which is easy to crack and pile up together. In addition, the energy gaps, UV–vis, luminescent and cyclic voltammetry were experimented to show the stable one dimensional long-chain chiral structure and the π function of two complexes.
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      PubDate: 2016-01-15T10:07:52Z
       
  • Chalcogen bonding interactions between reducible sulfur and selenium
           compounds and models of zinc finger proteins
    • Abstract: Publication date: Available online 12 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Patricia B. Lutz, Craig A. Bayse
      Reducible sulfur and selenium (r-S/Se) compounds, defined as sulfur and selenium compounds not in the lowest −2 oxidation state (e.g., −1 to +6), release Zn2+ from zinc-sulfur proteins such as zinc fingers (ZFs) and metallothionein. A series of density functional theory calculations were performed on donor–acceptor complexes between r-S/Se compounds and models of the Cys2His2, Cys3His and Cys4 ZF sites. These S⋯S/Se chalcogen bonding interactions consist of the donation of electron density from a S lone pair on the ZF model to a S/Se–X antibonding molecular orbital of the r-S/Se compound. The strength of the interaction was shown to be dependent upon the Lewis basicity of the ZF model (Cys4 >Cys3His>Cys2His2) and the Lewis acidity of the r-S/Se compound as measured by the energy of the S/Se–X antibonding orbital. Interactions with the softer r-Se compounds were stronger than the r-S compounds, consistent with the greater reactivity of the former with ZF proteins.
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      PubDate: 2016-01-15T10:07:52Z
       
  • Synthesis and structure elucidation of new μ-oxamido-bridged
           dicopper(II) complexes showing in vitro anticancer activity: Evaluation of
           DNA/protein-binding properties by experiment and molecular docking
    • Abstract: Publication date: March 2016
      Source:Journal of Inorganic Biochemistry, Volume 156
      Author(s): Kang Zheng, Fang Liu, Yan-Tuan Li, Zhi-Yong Wu, Cui-Wei Yan
      Two new μ-oxamido-bridged dicopper(II) complexes formulated as [Cu2(hmdoxd)(H2O)(Me2bpy)]-(ClO4)·DMF (1) and [Cu2(hmdoxd)(bpy)](ClO4)·CH3OH (2), where H3hmdoxd is N-(2-hydroxy-5-methylphenyl)-N′-[2-(dimethylamino)ethyl]oxamide; Me2bpy and bpy stand for 4,4′-dimethyl-2,2′-bipyridine and 2,2′-bipyridine, respectively, were synthesized and structurally characterized. The single-crystal X-ray diffraction analysis reveals that the copper(II) ions in complexes 1 and 2 are bridged by the cis-hmdoxd3− with corresponding Cu⋯Cu separations of 5.1596(6) and 5.1562(6) Å, respectively, in which the endo- and exo-copper(II) ions are located in square-planar and square-pyramidal geometries, respectively, for 1, and square-planar environments for 2. In the crystals of the two complexes, there are abundant hydrogen bonds and π–π stacking interactions contributing to the supramolecular structure. The DNA/protein-binding property of the two complexes are studied both theoretically and experimentally, indicating that complexes 1 and 2 can interact with DNA in the mode of intercalation and partial intercalation, respectively, and effectively bind to protein BSA via the favored binding sites Trp213 for 1 and Trp134 for 2. In vitro anticancer activities showed that the two complexes are active against the selected tumor cell lines, and the anticancer activities are consistent with their DNA/protein-binding affinities following the order of 1 > 2. The effect of the hydrophobicity of both the bridging and terminal ligands in the dicopper(II) complexes on DNA/protein-binding events and in vitro anticancer activities is preliminarily discussed.
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      PubDate: 2016-01-15T10:07:52Z
       
  • Comparative Raman study of four plant metallothionein isoforms: Insights
           into their Zn(II) clusters and protein conformations
    • Abstract: Publication date: March 2016
      Source:Journal of Inorganic Biochemistry, Volume 156
      Author(s): Mireia Tomas, Anna Tinti, Roger Bofill, Mercè Capdevila, Silvia Atrian, Armida Torreggiani
      Four Metallothioneins (MTs) from soybean (Glycine max) were heterologously synthesized and comparatively analysed by Raman spectroscopy. The participation of protein donor groups (S-thiol and N-imidazol) in Zn(II) chelation, as well as the presence of secondary structure elements was comparatively analysed. Metal clusters with different geometry can be hypothesised for the four GmMTs: a cubane-like or an adamantane-like metal cluster in Zn-GmMT1, and dinuclear Zn–S clusters in Zn-GmMT2, Zn-GmMT3 and Zn-GmMT4. The latter have also a similar average Cys/Zn content, whereas a lower ratio is present in Zn-GmMT1. This is possible thanks to the involvement in metal coordination of a greater number of bridging Cys, as well as of some carboxylate groups. As regards secondary structure elements, a large content of β-turn segments is present in all four Zn-GmMTs, especially for isoforms 1 and 4. β-strands give a contribution to the folding of three GmMTs isoforms, and the highest percentage was found in Zn-GmMT2 (~45%). Conversely, the α-helix content is negligible in all the GmMTs except in Zn-GmMT3, where this peculiar feature coincides with the possible involvement of the two His residues in metal coordination. Conversely, His is predominantly free and present as tautomer I in Zn-GmMT4. In conclusion, this work illustrates the attractive potential of Raman spectroscopy, combined with other techniques, to be a very informative tool for evidencing structural differences among in vivo synthesized metal-MT complexes.
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      PubDate: 2016-01-15T10:07:52Z
       
  • The studies on the cytotoxicity in vitro, cellular uptake, cell cycle
           arrest and apoptosis-inducing properties of ruthenium methylimidazole
           complex [Ru(MeIm)4(p-cpip)]2+
    • Abstract: Publication date: March 2016
      Source:Journal of Inorganic Biochemistry, Volume 156
      Author(s): Lan-mei Chen, Fa Peng, Guo-dong Li, Xin-ming Jie, Kang-rong Cai, Chun Cai, Yu Zhong, Hua Zeng, Wu Li, Zhen Zhang, Jin-can Chen
      A new ruthenium methylimidazole complex [Ru(MeIm)4(p-cpip)]2+ (Ru1, p-cpip=2-(4-chlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline, MeIm=1-methylimidazole) has been synthesized and characterized. The cellular uptake, in vitro cytotoxicities, cell cycle arrest and apoptosis-inducing mechanism of this Ru(II) complex have been extensively explored by Inductively Coupled Plasma Mass Spectrometry (ICP-MS), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, Comet assay, inverted fluorescence microscope as well as Western blotting experimental techniques. Notably, Ru1 displayed relatively high cytotoxic activity against lung cancer A549 cells and had high selectivity between tumor and normal cells in comparison with cisplatin. Further studies showed that Ru1 caused cell cycle arrest at G0/G1 phase and induced apoptosis via the mitochondrial pathway, which involved reactive oxygen species (ROS) accumulation, mitochondrial dysfunction and Bcl-2 and caspase correlative family member activation. For providing more information about the possible antitumor mechanism, the in vitro DNA binding studies have been also investigated by different spectrophotometric methods, thermal denaturation and viscosity measurements.
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      PubDate: 2016-01-15T10:07:52Z
       
  • ATOX1 gene silencing increases susceptibility to anticancer therapy based
           on copper ionophores or chelating drugs
    • Abstract: Publication date: Available online 11 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Vincenza Barresi, Giorgia Spampinato, Nicolò Musso, Angela Trovato Salinaro, Enrico Rizzarelli, Daniele Filippo Condorelli
      Copper is a catalytic cofactor required for the normal function of many enzymes involved in fundamental biological processes but highly cytotoxic when in excess. Therefore its homeostasis and distribution is strictly regulated by a network of transporters and intracellular chaperones. ATOX1 (Antioxidant Protein 1) is a copper chaperone that plays a role in copper homeostasis by binding and transporting cytosolic copper to ATPase proteins in the trans-Golgi network. In the present study the Caco-2 cell line, a colon carcinoma cell line, was used as in vitro model to evaluate if ATOX1 deficiency could affect sensitivity to experimentally induced copper dyshomeostasis. Silencing of ATOX1 increased toxicity of a short treatment with high concentration of Cu2+. Copper ionophores, such as 5-chloro-8-hydroxyquinoline, induced a copper-dependent cell toxicity which was significantly potentiated after ATOX1 silencing. The copper chelator TPEN (N,N,N’,N’-tetrakis (2-pyridylmethyl) ethylenediamine) produced a form of cell toxicity that was reversed by the addition of Cu2+. ATOX1 silencing increased Caco-2 cells sensitivity to TPEN toxicity. Our results suggest the possibility of a therapy with copper-chelating or ionophore drugs in subtypes of tumors showing specific alterations in ATOX1 expression.
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      PubDate: 2016-01-11T09:51:46Z
       
  • Distinct mechanisms for DNA cleavage by myoglobin with a designed heme
           active center
    • Abstract: Publication date: Available online 11 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Yuan Zhao, Ke-Jie Du, Shu-Qin Gao, Bo He, Ge-Bo Wen, Xiangshi Tan, Ying-Wu Lin
      Heme proteins perform diverse biological functions, of which myoglobin (Mb) is a representative protein. In this study, the O2 carrier Mb was shown to cleave double stranded DNA upon aerobic dithiothreitol-induced reduction, which is fine-tuned by an additional distal histidine, His29 or His43, engineered in the heme active center. Spectroscopic (UV–vis and EPR) and inhibition studies suggested that free radicals including singlet oxygen and hydroxyl radical are responsible for efficient DNA cleavage via an oxidative cleavage mechanism. On the other hand, L29E Mb, with a distinct heme active center involving three water molecules in the met form, was found to exhibit an excellent DNA cleavage activity that was not depending on O2. Inhibition and ligation studies demonstrated for the first time that L29E Mb cleaves double stranded DNA into both the nicked circular and linear forms via a hydrolytic cleavage mechanism, which resembles native endonucleases. This study provides valuable insights into the distinct mechanisms for DNA cleavage by heme proteins, and lays down a base for creating artificial DNA endonucleases by rational design of heme proteins. Moreover, this study suggests that the diverse functions of heme proteins can be fine-tuned by rational design of the heme active center with a hydrogen-bonding network.
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      PubDate: 2016-01-11T09:51:46Z
       
  • Synthesis, characterization and biological evaluation of novel
           Ru(II)–arene complexes containing intercalating ligands
    • Abstract: Publication date: Available online 11 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Stefan Nikolić, Loganathan Rangasamy, Nevenka Gligorijević, Sandra Aranđelović, Siniša Radulović, Gilles Gasser, Sanja Grgurić-Šipka
      Three new ruthenium(II)–arene complexes, namely [(η6-p-cymene)Ru(Me2dppz)Cl]PF6 (1), [(η6-benzene)Ru(Me2dppz)Cl]PF6 (2) and [(η6-p-cymene)Ru(aip)Cl]PF6 (3) (Me2dppz=11,12-dimethyldipyrido[3,2-a:2′,3′-c]phenazine; aip=2-(9-anthryl)-1H-imidazo[4,5-f] [1,10] phenanthroline) have been synthesized and characterized using different spectroscopic techniques including elemental analysis. The complexes were found to be well soluble and stable in DMSO. The biological activity of the three complexes was tested in three different human cancer cell lines (A549, MDA-MB-231 and HeLa) and in one human non-cancerous cell line (MRC-5). Complexes 1 and 3, carrying η 6-p-cymene as the arene ligand, were shown to be toxic in all cell lines in the low micromolar/subnanomolar range, with complex 1 being the most cytotoxic complex of the series. Flow cytometry analysis revealed that complex 1 caused concentration- and time-dependent arrest of the cell cycle in G2-M and S phases in HeLa cells. This event is followed by the accumulation of the sub-G1 DNA content after 48h, in levels higher than cisplatin and in the absence of phosphatidylserine externalization. Fluorescent microscopy and acridine orange/ethidium bromide staining revealed that complex 1 induced both apoptotic and necrotic cell morphology characteristics. Drug-accumulation and DNA-binding studies performed by inductively coupled plasma mass spectrometry in HeLa cells showed that the total ruthenium uptake increased in a time- and concentration-dependent manner, and that complex 1 accumulated more efficiently than cisplatin at equimolar concentrations. The introduction of a Me2dppz ligand into the ruthenium(II)-p-cymene scaffold was found to allow for the discovery of a strongly cytotoxic complex with significantly higher cellular uptake and DNA-binding properties than cisplatin.
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      PubDate: 2016-01-11T09:51:46Z
       
  • Dinuclear ruthenium complexes display loop isomer selectivity to c-MYC DNA
           G- quadriplex and exhibit anti-tumor activity
    • Abstract: Publication date: Available online 11 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Chuping Zheng, Yanan Liu, Ying Liu, Xiuying Qin, Yanhui Zhou, Jie Liu
      G-quadruplex DNA, especially the cellular-myelocytomatosis viral oncogene (c-MYC) is closely associated with cell-cycle regulation, proliferation of tumour cells. In this work, the interaction between the c-MYC and two dinuclear Ru(II) complexes [(bpy)2Ru(bpibp)Ru(bpy)2](ClO4)4 (compound 1) and [(phen)2Ru(bpibp)Ru(phen)2](ClO4)4 (compound 2) have been studied. The data from UV–Visible, PCR-stop and Fluorescence resonance energy transfer (FRET) showed that two complexes can stabilize the structure of G-quadruplex in the c-MYC promoter and targeting the G-quadruplex loop isomers. Interestingly, the complex 2 has a greater effect on the 1:2:1 and 2:1:1 loop isomers while the 1 prefer to the 1:2:1 isomers. The mechanism studies revealed that complexes can induce apoptosis in HepG2 cells by generating ROS metabolites, triggering mitochondrial membrane potential loss and down-regulation of P-Akt (Akt also known as protein kinase B), P- p44/42 MAP kinase protein (P- p44/42), and c-MYC. Taken together, these results sugested that the two dinuclear complexes may both be candidates as anti-tumour agents as they may reduce the c-MYC gene expression. {bpibp: 4, 4′-bis (1, 10-phenanthroline-[5, 6-d] imidazole-2-yl)-biphenyl, bpy: 2,2-bipyridine, phen: 1,10-phenanthroline}
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      PubDate: 2016-01-11T09:51:46Z
       
  • Dimerization and DNA recognition rules of mithramycin and its analogues
    • Abstract: Publication date: March 2016
      Source:Journal of Inorganic Biochemistry, Volume 156
      Author(s): Stevi Weidenbach, Caixia Hou, Jhong-Min Chen, Oleg V. Tsodikov, Jürgen Rohr
      The antineoplastic and antibiotic natural product mithramycin (MTM) is used against cancer-related hypercalcemia and, experimentally, against Ewing sarcoma and lung cancers. MTM exerts its cytotoxic effect by binding DNA as a divalent metal ion (Me2+)-coordinated dimer and disrupting the function of transcription factors. A precise molecular mechanism of action of MTM, needed to develop MTM analogues selective against desired transcription factors, is lacking. Although it is known that MTM binds G/C-rich DNA, the exact DNA recognition rules that would allow one to map MTM binding sites remain incompletely understood. Towards this goal, we quantitatively investigated dimerization of MTM and several of its analogues, MTM SDK (for Short side chain, DiKeto), MTM SA-Trp (for Short side chain and Acid), MTM SA-Ala, and a biosynthetic precursor premithramycin B (PreMTM B), and measured the binding affinities of these molecules to DNA oligomers of different sequences and structural forms at physiological salt concentrations. We show that MTM and its analogues form stable dimers even in the absence of DNA. All molecules, except for PreMTM B, can bind DNA with the following rank order of affinities (strong to weak): MTM=MTM SDK>MTM SA-Trp>MTM SA-Ala. An X(G/C)(G/C)X motif, where X is any base, is necessary and sufficient for MTM binding to DNA, without a strong dependence on DNA conformation. These recognition rules will aid in mapping MTM sites across different promoters towards development of MTM analogues as useful anticancer agents.
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      PubDate: 2016-01-07T09:33:59Z
       
  • “Sustaining Life on Planet Earth: Metalloenzymes Mastering Dioxygen
           and Other Chewy Gases”, Metal Ions in Life Sciences, Volume 15,
           Guest editors: Peter M.H. Kroneck, Martha E. Sosa Torres, Series editors:
           Astrid Sigel, Helmut Sigel, Roland K.O. Sigel, Springer International
           Publishing AG, Switzerland, 2015, 329 pp. [ISSN 1559-0836; ISSN 1868-0402
           (electronic); ISBN 978-3-319-12414-8; ISBN 978-3-319-12415-5 (eBook); DOI
           10.1007/978-3-319-12415-5].
    • Abstract: Publication date: March 2016
      Source:Journal of Inorganic Biochemistry, Volume 156
      Author(s): Liliana Quintanar



      PubDate: 2016-01-07T09:33:59Z
       
  • Selective binding and magnetic separation of histidine-tagged proteins
           using Fe3O4/Cu-apatite nanoparticles
    • Abstract: Publication date: Available online 30 December 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Ping Li, Liangliang Li, Yanbao Zhao, Lei Sun, Yu Zhang
      Hierarchical Fe3O4@Cu-apatite nanoparticles (NPs) were synthesized via a facile hydrothermal method. The Fe3O4 cores present spherical shape and have a mean diameter of 300 nm, and the Cu-apatite shell with thickness of about 50 nm is composed of a large number of sheets. Using the high affinity of Cu2+ on the surface toward histidine tags, the Fe3O4@Cu-apatite NPs can be applied to enrich and magnetically separate histidine tagged (His-tagged) proteins directly from the mixture of lysed cells. Research results indicated that the Fe3O4@Cu-apatite NPs presented negligible nonspecific protein adsorption and high protein binding ability.
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      PubDate: 2016-01-02T22:50:50Z
       
  • Ruthenium(II) complexes of 1,3-thiazolidine-2-thione: cytotoxicity against
           tumor cells and anti-Trypanosoma cruzi activity enhanced upon combination
           with benznidazole
    • Abstract: Publication date: Available online 2 January 2016
      Source:Journal of Inorganic Biochemistry
      Author(s): Rodrigo S. Corrêa, Monize M. da Silva, Angelica E. Graminha, Cássio S. Meira, Jamyle A.F. dos Santos, Diogo R.M. Moreira, Milena B.P. Soares, Gustavo Von Poelhsitz, Eduardo E. Castellano, Carlos Bloch, Marcia R. Cominetti, Alzir A. Batista
      Three new mixed and mononuclear Ru(II) complexes containing 1,3-thiazolidine-2-thione (tzdtH) were synthesized and characterized by spectroscopic analysis, molar conductivity, cyclic voltammetry, high-resolution electrospray ionization mass spectra and X-ray diffraction. The complexes presented unique stereochemistry and the proposed formulae are: [Ru(tzdt)(dppb)(bipy)]PF6 (1), cis-[Ru(tzdt)2(PPh3)2] (2) and trans-[Ru(tzdt)(PPh3)2(bipy)]PF6 (3), where dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2’-bipyridine. These complexes demonstrated strong cytotoxicity against cancer cell lines when compared to cisplatin. Specifically, complex 2 was the most potent cytotoxic agent against MCF-7 breast cells, while complexes 1 and 3 were more active in DU-145 prostate cells. Binding of complexes to ctDNA was determined by UV-vis titration and viscosity measurements and revealed binding constant (Kb) values in range of 1.0-4.9x103 M-1, which are characteristic of compounds possessing weak affinity to ctDNA. In addition, these complexes presented antiparasitic activity against Trypanosoma cruzi. Specifically, complex 3 demonstrated strong potency, moderate selectivity index and acted in synergism with the approved antiparasitic drug, benznidazole. Additionally, complex 3 caused parasite cell death through a necrotic process. In conclusion, we demonstrated that Ru(II) complexes have powerful pharmacological activity, while the metal-free tzdtH does not provoke the same outcome.
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      PubDate: 2016-01-02T22:50:50Z
       
  • Investigating the position of the hairpin loop in New Delhi
           metallo-β-lactamase, NDM-1, during catalysis and inhibitor binding
    • Abstract: Publication date: March 2016
      Source:Journal of Inorganic Biochemistry, Volume 156
      Author(s): Mahesh Aitha, Abraham J. Moller, Indra D. Sahu, Masaki Horitani, David L. Tierney, Michael W. Crowder
      In an effort to examine the relative position of a hairpin loop in New Delhi metallo-β-lactamase, NDM-1, during catalysis, rapid freeze quench double electron electron resonance (RFQ-DEER) spectroscopy was used. A doubly-labeled mutant of NDM-1, which had one spin label on the invariant loop at position 69 and another label at position 235, was prepared and characterized. The reaction of the doubly spin labeled mutant with chromacef was freeze quenched at 500μs and 10ms. DEER results showed that the average distance between labels decreased by 4Å in the 500μs quenched sample and by 2Å in the 10ms quenched sample, as compared to the distance in the unreacted enzyme, although the peaks corresponding to distance distributions were very broad. DEER spectra with the doubly spin labeled enzyme with two inhibitors showed that the distance between the loop residue at position 69 and the spin label at position 235 does not change upon inhibitor binding. This study suggests that the hairpin loop in NDM-1 moves over the metal ion during the catalysis and then moves back to its original position after hydrolysis, which is consistent with a previous hypothesis based on NMR solution studies on a related metallo-β-lactamase. This study also demonstrates that this loop motion occurs in the millisecond time domain.
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      PubDate: 2015-12-25T22:09:24Z
       
  • Editorial Board
    • Abstract: Publication date: February 2016
      Source:Journal of Inorganic Biochemistry, Volume 155




      PubDate: 2015-12-21T21:59:05Z
       
  • Contents
    • Abstract: Publication date: February 2016
      Source:Journal of Inorganic Biochemistry, Volume 155




      PubDate: 2015-12-21T21:59:05Z
       
  • Prediction of logP for Pt(II) and Pt(IV) complexes: Comparison of
           statistical and quantum-chemistry based approaches
    • Abstract: Publication date: Available online 11 December 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Igor V. Tetko, Hristo P. Varbanov, Markus Galanski, Mona Talmaciu, Jamie Platts, Mauro Ravera, Elisabetta Gabano
      The octanol/water partition coefficient, logP, is one of the most important physico-chemical parameters for the development of new metal-based anticancer drugs with improved pharmacokinetic properties. This study addresses an issue with the absence of publicly available models to predict logP of Pt(IV) complexes. Following data collection and subsequent development of models based on 187 complexes from literature, we validate new and previously published models on a new set of 11 Pt(II) and 35 Pt(IV) complexes, which were kept blind during the model development step. The error of the consensus model, 0.65 for Pt(IV) and 0.37 for Pt(II) complexes, indicates its good accuracy of predictions. The lower accuracy for Pt(IV) complexes was attributed to experimental difficulties with logP measurements for some poorly-soluble compounds. This model was developed using general-purpose descriptors such as extended functional groups, molecular fragments and E-state indices. Surprisingly, models based on quantum-chemistry calculations provided lower prediction accuracy. We also found that all the developed models strongly overestimate logP values for the three complexes measured in the presence of DMSO. Considering that DMSO is frequently used as a solvent to store chemicals, its effect should not be overlooked when logP measurements by means of the shake flask method are performed. The final models are freely available at http://ochem.eu/article/76903.
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      PubDate: 2015-12-13T18:07:42Z
       
  • Palladium(II) complexes with tris(2-carboxyethyl)phosphine, structure,
           reactions and cytostatic activity
    • Abstract: Publication date: Available online 9 December 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Hanna Pruchnik, Tadeusz Lis, Małgorzata Latocha, Aleksandra Zielińska, Florian P. Pruchnik
      Water soluble and air stable P(RCOOH)3 (R=C2H4) (TCEP) is an efficient reducing agent used in biochemistry to break S–S bond in peptides, proteins and other compounds containing S–S bonds. The similarity between the coordination chemistry of Pd(II) and Pt(II) led to the investigations of antitumor activity of palladium(II) compounds however the Pd(II) complexes with TCEP were not investigated. New palladium(II) complexes with (TCEP): trans-[PdCl2(TCEP)2] (1) and trans-[Pd2(μ-Cl)2Cl2(TCEP)2] (2) were fully characterized by 1H, 13C, 31P NMR, IR and ESI-MS spectroscopic techniques. Complexes are stable in non-aqueous DMSO and DMF. In aqueous solutions Cl ligands are substituted by COO groups of phosphines. Complex 2, after crystallization from water gives polymeric compound with bridging phosphine ligand [PdCl{P(RCOO-κO-μ-O′)(RCOOH)2-κP}] (3). Structures of trans-[PdCl2{P(RCOOD)3}2] (1a), trans-[Pd2(μ-Cl)2PdCl2{P(RCOOD)3}2] (2a), and [PdCl{P(RCOO-κO-μ-O′)(RCOOD)2-κP}]n (3a) have been determined by X-ray crystallography. NMR and ESI-MS spectra reveal that [PdP2(RCOO-κO)2(RCOO)n(RCOOH)4−n]n – complexes are formed in aqueous solution of 1. Geometry optimization in the gas phase at the B3LYP/3-21G** level indicated that complex 2 with butterfly structure is more stable than that with coplanar coordination. In aqueous solution of 2, the main products [Pd2{P(RCOO-κO-μ-O′)(RCOO-κO)(RCOOH)}2] and [Pd{P(RCOO-κO)2(RCOOH)}(H2O)] exist in equilibrium which depends on temperature: content of mononuclear compound increases as the temperature is raised. Complexes 1 and 2 are active agents against melanoma and breast cancer cells.
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      PubDate: 2015-12-10T17:51:32Z
       
  • Novel enantiopure cyclopentadienyl Ti(IV) oximato compounds as potential
           anticancer agents
    • Abstract: Publication date: Available online 9 December 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Isabel de la Cueva-Alique, Laura Muñoz-Moreno, Yosra Benabdelouahab, Benelita T. Elie, Mohammed Amin El Amrani, Marta E.G. Mosquera, María Contel, Ana M. Bajo, Tomás Cuenca, Eva Royo
      The synthesis and characterization of new enantiopure cyclopentadienyl titanium oximato compounds (S,R)-[(η5-C5H5)Ti{к 2 NO,(R)NH·HCl}Cl2] (R=Ph (phenyl) 1a·HCl, Bn (benzyl) 1b·HCl, 2-pic (2-picolyl) 1c·HCl), (S,R)-[(η5-C5H5)TiCl2{к 2 NO,(Ph)NH}] (1a) and (S,R)-[(η5-C5H5)2TiCl{к 2 NO,(R)NH}] (R=Ph 2a, Bn 2b, 2-pic 2c), along with studies on their behaviour in D2O at different pD values are reported. The structure of previously described ammonium-oxime (2S,5R)-{NOH,(Bn)NH·HCl} (b·HCl) and novel titanium derivative 1a have been determined by single crystal X-ray crystallography. The effect of the compounds on cytotoxicity, cell adhesion and migration of the androgen-independent prostate cancer PC-3 cells has been assessed. Compounds 2b and 2c are more cytotoxic than additive doses of titanocene dichloride and free oxime proligand, probing the synergistic effect of these novel compounds. The cytotoxicity of 2b and 2c has been further evaluated against human renal Caki-1, colon DLD-1 and triple negative breast MDA-MB-231 cancer cell lines. The activity found for 2c on PC-3 and Caki-1 is higher than that of highly active Titanocene Y (bis-[(p-methoxybenzyl)cyclopentadienyl]titanium(IV) dichloride), while showing selectivity against renal cancer when compared to a non-tumorigenic human renal (HEK-293T) cell line. Compounds 2b and especially 2c are apoptotic in Caki-1 cancer cell lines. Cell adhesion and wound-healing assays confirmed that derivatives 1c·HCl, 2b and 2c affect the adhesion and migration patterns of the PC-3 cell line. Interactions of the novel compounds with plasmid (pBR322) DNA have also been studied, showing that the oximato Ti(IV) derivatives have a weak or no interaction with DNA at physiological pH.
      Graphical abstract image

      PubDate: 2015-12-10T17:51:32Z
       
  • Palladium-benzodiazepine derivatives as promising metallodrugs for the
           development of antiepileptic therapies
    • Abstract: Publication date: Available online 2 December 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Walleska Bismaida Zacarias Galvão Barros, Allysson Haide Queiroz da Silva, Ana Soraya Lima Barbosa, Ábner Magalhães Nunes, José Rui Machado Reys, Heitor Gomes de Araújo-Filho, Jullyana de Souza Siqueira Quintans, Lucindo José Quintans-Júnior, Michel Pfeffer, Valéria Rodrigues dos Santos Malta, Mario Roberto Meneghetti
      We synthesized two organometallic diazepam-palladium(II) derivatives by C-H activation of diazepam (DZP) with palladium salts, i.e., PdCl2 and Pd(OAc)2. Both compounds obtained are air stable and were isolated in good yields. The anticonvulsant potential of the complexes, labeled [(DZP)PdCl] 2 and [(DZP)PdOAc] 2 , was evaluated through two animal models: pentylenetetrazole (PTZ)- and picrotoxin (PTX)-induced convulsions. The organometallic DZP-palladium(II) acetate complex, [(DZP)PdOAc] 2 , significantly increased (p <0.01 or p <0.001) latencies and protected the animals against convulsions induced by PTZ and PTX, while the analogous chloro derivative, [(DZP)PdCl] 2 , was effective (p <0.01) only in the PTZ model. These effects appear to be mediated through the GABAergic system. The possible mechanism of action of the DZP-palladium(II) complexes was also confirmed with the use of flumazenil (FLU), a GABAA-benzodiazepine receptor complex site antagonist. Herein, we present the first report of the anticonvulsant properties of organometallic DZP-palladium(II) complexes as well as evidence that these compounds may play an important role in the study of new drugs to treat patients with epilepsy.
      Graphical abstract image

      PubDate: 2015-12-02T17:27:06Z
       
  • Synthesis of platinum complexes with
           2-(5-perfluoroalkyl-1,2,4-oxadiazol-3yl)-pyridine and
           2-(3-perfluoroalkyl-1-methyl-1,2,4-triazole-5yl)-pyridine ligands and
           their in vitro antitumor activity
    • Abstract: Publication date: Available online 1 December 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Simona Rubino, Ivana Pibiri, Cristina Costantino, Silvestre Buscemi, Maria Assunta Girasolo, Alessandro Attanzio, Luisa Tesoriere
      Five new mononuclear Pt(II) complexes with 5-perfluoroalkyl-1,2,4-oxadiazolyl-pyridine and 3-perfluoroalkyl-1,2,4-triazolyl-pyridine ligands are reported. The ligands 2-(5-perfluoroheptyl-1,2,4-oxadiazole-3yl)-pyridine (pfhop), 2-(5-perfluoropropyl)-1,2,4-oxadiazole-3yl)-pyridine (pfpop), 2-(3-perfluoroheptyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfhtp), 2-(3-perfluoropropyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfptp) and their complexes [PtCl2(pfhop)2]·1.5 DMSO (2a), [PtCl2(pfpop)2]·1.5 DMSO (3a), [PtCl2(pfhtp)2]·1.5 DMSO (4a), PtCl2(pfhtp) (4b), [PtCl2(pfptp)2]·1.5 DMSO (5a) have been synthesized and structurally characterized. The complexes 2a, 3a, 4a and 5a have the same chemical environment of Pt(II) where PtCl2 moieties coordinate two molecules of ligand via N1 atom of pyridine in the case of pfhop and pfpop, and N2 atom of 1,2,4-triazole in the case of pfhtp and pfptp. For 4b, pfhtp behaves as bidentate ligand, coordinating Pt(II) ion via N4 atom of triazole and N1 atom of pyridine. All complexes have been tested in vitro by 3-(4,5-dimethyl-2-thiazolyl)bromide-2,5-diphenyl-2H-tetrazolium (MTT) test on four tumor cell lines MCF-7 (human breast cancer), HepG2 (human hepatocellular carcinoma), HCT116 (human colorectal carcinoma). Compounds 2a and 4b showed a dose-dependent anti-proliferative effect against the three tumor cell lines whereas did not affect viability of intestinal normal-like differentiated Caco-2 cells. The cell death of HepG2, MCF-7 and HCT116 induced by the compounds, was considered to be apoptotic by measuring the exposure of phosphatidylserine to the outer membrane and observing the typical apoptotic morphological change by acridine orange (AO)/ethidium bromide (EB) staining.
      Graphical abstract image

      PubDate: 2015-12-02T17:27:06Z
       
  • Silver(I) complexes with phthalazine and quinazoline as effective agents
           against pathogenic Pseudomonas aeruginosa strains
    • Abstract: Publication date: Available online 2 December 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Biljana Đ. Glišić, Lidija Senerovic, Peter Comba, Hubert Wadepohl, Aleksandar Veselinovic, Dušan R. Milivojevic, Miloš I. Djuran, Jasmina Nikodinovic-Runic
      Five silver(I) complexes with aromatic nitrogen-containing heterocycles, phthalazine (phtz) and quinazoline (qz), were synthesized, characterized and analyzed by single-crystal X-ray diffraction analysis. Although different AgX salts reacted with phtz, only dinuclear silver(I) complexes of the general formula {[Ag(X-O)(phtz-N)]2(μ-phtz-N,N’)2} were formed, X=NO3 − (1), CF3SO3 − (2) and ClO4 − (3). However, reactions of qz with an equimolar amount of AgCF3SO3 and AgBF4 resulted in the formation of polynuclear complexes, {[Ag(CF3SO3-O)(qz-N)]2}n (4) and {[Ag(qz-N)][BF4]}n (5). Complexes 1–5 were evaluated by in vitro antimicrobial studies against a panel of microbial strains that lead to many skin and soft tissue, respiratory, wound and nosocomial infections. The obtained results indicate that all tested silver(I) complexes have good antibacterial activity with MIC (minimum inhibitory concentration) values in the range from 2.9 to 48.0μM against the investigated strains. Among the investigated strains, these complexes were particularly efficient against pathogenic Pseudomonas aeruginosa (MIC =2.9–29μM) and had a marked ability to disrupt clinically relevant biofilms of strains with high inherent resistance to antibiotics. On the other hand, their activity against the fungus Candida albicans was moderate. In order to determine the therapeutic potential of silver(I) complexes 1–5, their antiproliferative effect on the human lung fibroblastic cell line MRC5, has been also evaluated. Binding of complexes 1–5 to the genomic DNA of P. aeruginosa was demonstrated by gel electrophoresis techniques and well supported by molecular docking into the DNA minor groove. All investigated complexes showed an improved cytotoxicity profile in comparison to the clinically used AgNO3.
      Graphical abstract image

      PubDate: 2015-12-02T17:27:06Z
       
  • Interaction of metallacrown complexes with G-quadruplex DNA
    • Abstract: Publication date: Available online 2 December 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Ewa Rajczak, Agata Gluszynska, Bernard Juskowiak
      Interactions of the G-quadruplex (GQ) DNA with two pentacoordinate lanthanide (III) metallacrown complexes containing phenylalanine hydroxamic acid (pheHA) and copper(II) ions of the formula Eu 15-[MCCu,pheHA]-5 (1) and Tb 15-[MCCu,pheHA]-5 (2) were investigated. Binding of both metallacrowns to human telomeric G-quadruplex DNA was followed using CD spectroscopy, DNA melting profiles, and fluorescent intercalator displacement (FID) assay. A new G-quadruplex binding assay based of quenching of Tb(III)-GQ luminescence was proposed and evaluated. All performed tests confirmed interactions of MCs with studied GQ structure. Binding affinities of MCs were appreciable (KMC ~ 2-5x105 M-1). Higher concentration of MCs (the ratio of GQ:MC above 2.5) caused destabilization of tetraplex structure of GQ as evidenced by CD spectroscopy, melting temperatures, and Tb(III)-GQ luminescence quenching results.
      Graphical abstract image

      PubDate: 2015-12-02T17:27:06Z
       
  • Effect of concomitant oxidation and deprotonation of hydrated Mn centres
           in rationalising the FTIR difference silence of D1–Asp170 in
           photosystem II
    • Abstract: Publication date: Available online 25 November 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Richard Terrett, Terry Frankcombe, Ron Pace, Robert Stranger
      The observation of negligible FTIR differences in carboxylate vibrational modes for the D1–Asp170 residue of Photosystem II (PSII) on successive one–electron oxidations of the Mn4CaO5 oxygen–evolving complex (OEC) is counterintuitive in light of the apparent ligation of D1–Asp170 to an oxidisable Mn ion in the X–ray crystallographic structures of PSII. Here, we show computational support for the hypothesis that suppression of the FTIR difference spectrum in the 1100cm−1 to 1700cm−1 region of D1–Asp170 occurs by concomitant Mn oxidation and deprotonation of water ligands bound to the ligated metal centre. Density functional theory calculations on the model species [MnIICa(COOH)(OH)2(H2O)2]+ over two successive oxidations of the Mn ion are performed, where those oxidations are accompanied by deprotonation of water and μ–hydroxo ligands coordinated to the Mn ion. In contrast, dramatically increased FTIR difference activity is observed where these oxidations are unaccompanied by proton loss.
      Graphical abstract image

      PubDate: 2015-11-27T17:12:45Z
       
  • Second sphere control of spin state: Differential tuning of axial ligand
           bonds in ferric porphyrin complexes by hydrogen bonding
    • Abstract: Publication date: Available online 19 November 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Kaustuv Mittra, Kushal Sengupta, Asmita Singha, Sabyasachi Bandyopadhyay, Sudipta Chatterjee, Atanu Rana, Subhra Samanta, Abhishek Dey
      An iron porphyrin with a pre-organized hydrogen bonding (H-Bonding) distal architecture is utilized to avoid the inherent loss of entropy associated with H-Bonding from solvent (water) and mimic the behavior of metallo-enzyme active sites attributed to H-Bonding interactions of active site with the 2nd sphere residues. Resonance Raman (rR) data on these iron porphyrin complexes indicate that H-Bonding to an axial ligand like hydroxide can result in both stronger or weaker Fe(III)-OH bond relative to iron porphyrin complexes. The 6-coordinate (6C) complexes bearing water derived axial ligands, trans to imidazole or thiolate axial ligand with H-Bonding stabilize a low spin(LS) ground state(GS) when a complex without H-Bonding stabilize a high spin(HS) ground state. DFT calculations reproduce the trend in the experimental data and provide a mechanism of how H-Bonding can indeed lead to stronger metal ligand bonds when the axial ligand donates an H-Bond and lead to weaker metal ligand bonds when the axial ligand accepts an H-Bond. The experimental and computational results explain how a weak Fe(III)-OH bond (due to H-Bonding) can lead to the stabilization of low spin ground state in synthetic mimics and in enzymes containing iron porphyrin active sites. H-Bonding to a water ligand bound to a reduced ferrous active site can only strengthen the Fe(II)-OH2 bond and thus exclusion of water and hydrophilic residues from distal sites of O2 binding/activating heme proteins is necessary to avoid inhibition of O2 binding by water. These results help demonstrate the predominant role played by H-Bonding and subtle changes in its orientation in determining the geometric and electronic structure of iron porphyrin based active sites in nature.
      Graphical abstract image

      PubDate: 2015-11-24T17:07:42Z
       
  • Photochemical studies and nanomolar photodynamic activities of
           phthalocyanines functionalized with 1,4,7-trioxanonyl moieties at their
           non-peripheral positions
    • Abstract: Publication date: Available online 14 November 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Lukasz Sobotta, Marcin Wierzchowski, Michal Mierzwicki, Zofia Gdaniec, Jadwiga Mielcarek, Leentje Persoons, Tomasz Goslinski, Jan Balzarini
      Manganese(III), cobalt(II), copper(II), magnesium(II), zinc(II) and metal-free phthalocyanines, possessing 1,4,7-trioxanonyl substituents, at their non-peripheral positions, were subjected to photochemical, photodynamic and biological activity studies. Demetallated Phthalocyanine and its metallated d-block analogues, with copper(II), cobalt(II), manganese(III) chloride, were found to be less efficient singlet oxygen generators in comparison to the zinc(II) analogue and zinc(II) phthalocyanine reference. Irradiation of several phthalocyanines for short time periods resulted in a substantially increased cytostatic activity against both suspension (leukemic/lymphoma at 85nM) and solid (cervix carcinoma at 72nM and melanoma at 81nM) tumor cell lines (up to 200-fold). Noteworthy is that enveloped viruses, such as for herpesvirus and influenza A virus, but not, non-enveloped virus strains, such as Coxsackie B4 virus and reovirus-1, exposed to irradiation in the presence of the phthalocyanines, markedly lost their infectivity potential.
      Graphical abstract image

      PubDate: 2015-11-20T16:54:29Z
       
  • Antimicrobial evaluation of new metallic complexes with xylitol active
           against P. aeruginosa and C. albicans: MIC determination, post-agent
           effect and Zn-uptake
    • Abstract: Publication date: Available online 11 November 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): E. Santi, G. Facchin, R. Faccio, R.P. Barroso, A.J. Costa-Filho, G. Borthagaray, M.H. Torre

      Graphical abstract image

      PubDate: 2015-11-15T16:51:01Z
       
  • Synthesis, crystal structure, DNA and protein binding studies of new novel
           binuclear Pd(II) complex of
           
    • Abstract: Publication date: Available online 11 November 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Eswaran Ramachandran, Roberta Bertani, Paolo Sgarbossa, Karuppannan Natarajan, Nattamai S.P. Bhuvanesh
      A novel binuclear palladium(II) complex [(AsPh3)2ClPd(L)PdCl] (LPd2) has been synthesized by reacting 2-oxo-1,2-dihydroquinoline-3-carbaldehyde-4(N,N)-dimethylthiosemicarbazone (HL) with [PdCl2(AsPh3)2], and the molecular structure was confirmed by single crystal X-ray diffraction studies. The DNA interactions of the free ligand and of the complex has been evaluated by absorption and ethidium bromide (EB) competitive studies which revealed that the complex could interact with calf thymus DNA (CT-DNA) through intercalation. In addition, the interactions with bovine serum albumin were also studied showing that the new binuclear palladium complex had a strong binding affinity with BSA.
      Graphical abstract image

      PubDate: 2015-11-15T16:51:01Z
       
  • Specific binding modes of Cu(I) and Ag(I) with neurotoxic domain of the
           human prion protein
    • Abstract: Publication date: Available online 11 November 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Daniela Valensin, Emilia Maria Padula, Aleksandra Hecel, Marek Luczkowski, Henryk Kozlowski
      Prion diseases are neurodegenerative disorders associated with a conformational change of the normal cellular isoform of the Prion Protein (PrPC) to an abnormal scrapie isoform (PrPSc). Human Prion Protein (hPrPC) is able to bind up to six Cu(II) ions. Four of them are distribuited in the octarepeat domain, containing four tandem-repetitions of the sequence PHGGGWGQ. Immediately outside the octarepeat domain, in so called PrP amyloidogenic region, two additional and independent Cu(II) binding sites, encompassing His96 and His111 residues, respectively, are present. Considering the potential involvement of PrP in cellular redox homeostasis, investigations on Cu(I)-PrP interaction might be also biologically relevant. Interestingly, the amyloidogenic fragment of PrP contains a –M(X)nM– motif, known to act as Cu(I) binding site in different proteins. In order to shed more light on this issue, copper(I) and silver(I) interactions with model peptides derived from that region were analyzed. The results of our studies reveal that both metal ions are anchored to two thioether sulfurs of Met109 and Met112, respectively. Subsequent metal interaction and coordination to His96 and His111 imidazoles is primarily found for Cu(I) at physiological pH. Metal binding was also investigated in presence of negatively charged micelles formed by the anionic surfactant, sodium dodecyl sulfate (SDS). Our results strongly support that metal binding mode strongly depends on the protein backbone structure. In particular we show that α-helix structuring of the amyloid PrP domain influences both the metal coordination sphere and the binding affinity.
      Graphical abstract image

      PubDate: 2015-11-15T16:51:01Z
       
  • Pd2+-mediated base pairing in oligonucleotides
    • Abstract: Publication date: Available online 11 November 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Oleg Golubev, Guillaume Turc, Tuomas Lönnberg
      Two short glycol nucleic acid (GNA) oligonucleotides, having either a terminal or an intrachain nucleobase replaced by the pyridine-2,6-dicarboxamide chelate of Pd2+, have been synthesized and their hybridization properties studied by melting temperature measurements. In the termini of a double-stranded oligonucleotide, the Pd2+ chelates provided dramatic stabilization of the duplex relative to its metal-free counterpart, in all likelihood owing to formation of Pd2+-mediated base pairs between pyridine-2,6-dicarboxamide and the opposing nucleobase. In contrast, no stabilization was observed when the Pd2+ chelate was placed in the middle of the chain. Furthermore, the results could not be reproduce by adding a Pd2+ salt in situ to the dilute oligonucleotide solutions but the palladated oligonucleotides had to be synthesized and purified prior to the hybridization studies. This behavior, presumably attributable to the relatively slow ligand-exchange reactions of Pd2+, differs greatly from what is usually observed with more labile metal ions. The present results offer an explanation for the failure of previous attempts to incorporate Pd2+-mediated base pairs into oligonucleotides.
      Graphical abstract image

      PubDate: 2015-11-15T16:51:01Z
       
  • Water soluble heterometallic potassium-dioxidovanadium(V) complexes as
           potential antiproliferative agents
    • Abstract: Publication date: Available online 11 November 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Manas Sutradhar, Alexandra R. Fernandes, Joana Silva, Kamran T. Mahmudov, M. Fátima C. Guedes da Silva, Armando J.L. Pombeiro

      Graphical abstract image

      PubDate: 2015-11-15T16:51:01Z
       
  • Structure-function relationships in human cytochrome c: The role of
           tyrosine 67
    • Abstract: Publication date: Available online 12 November 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Lorenzo Tognaccini, Chiara Ciaccio, Valentina D'Oria, Manuela Cervelli, Barry D. Howes, Massimo Coletta, Paolo Mariottini, Giulietta Smulevich, Laura Fiorucci
      Spectroscopic and functional properties of human cytochrome c and its Tyr67 residue mutants (i.e., Tyr67His and Tyr67Arg) have been investigated. In the case of the Tyr67His mutant we have observed only a very limited structural alteration of the heme pocket and of the Ω-loop involving, among others, the residue Met80 and its bond with the heme iron. Conversely, in the Tyr67Arg mutant the Fe-Met80 bond is cleaved; consequently, a much more extensive structural alteration of the Ω-loop can be envisaged. The structural, and thus the functional modifications, of the Tyr67Arg mutant are present in both the ferric [Fe(III)] and the ferrous [Fe(II)] forms, indicating that the structural changes are independent on the heme iron oxidation state, depending instead on the type of substituting residue. Furthermore, a significant peroxidase activity is evident for the Tyr67Arg mutant, highlighting the role of Arg as a basic, positively charged residue at pH7.0, located in the heme distal pocket, which may act as an acid to cleave the O-O bond in H2O2. As a whole, our results indicate that a delicate equilibrium is associated with the spatial arrangement of the Ω-loop. Clearly, Arg, but not His, is able to stabilize and polarize the negative charge on the Fe(III)-OOH complex during the formation of Compound I, with important consequences on cytochrome peroxidation activity and its role in the apoptotic process, which is somewhat different in yeast and mammals.
      Graphical abstract image

      PubDate: 2015-11-15T16:51:01Z
       
  • Cytochrome unfolding pathways from computational analysis of crystal
           structures
    • Abstract: Publication date: Available online 10 November 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): John J. Kozak, Harry B. Gray, Roberto A. Garza-López
      We have developed a model to study the role of geometrical factors in influencing the early stages of unfolding in three cytochromes: cyt c’, cyt c-b 562 and cyt c. Each stage in unfolding is quantified by the spatial extension λ ̂ i of n-residue segments, and by their angular extension 〈β n 〉. Similarities and differences between and among the three cytochromes in the unfolding of helical and non-helical regions can be determined by analyzing the data for each signature separately. Definite conclusions can be drawn when spatial and angular changes are considered in tandem. To facilitate comparisons, we present graphical portraits of the three cytochromes at the same stage of unfolding, and in relation to their native state structures. We also display specific segments at different stages of unfolding to illustrate differences in stability of defined domains thereby allowing us to make specific predictions on the unfolding of corresponding internal and terminal helices in cyt c’ and cyt c-b 562. Our work accords with an earlier experimental report on the presence and persistence of a hydrophobic core in cyt c.
      Graphical abstract image

      PubDate: 2015-11-11T16:47:44Z
       
  • Uncovering novel 3-hydroxy-4-pyridinone metal ion complexes with potential
           anti-inflammatory properties
    • Abstract: Publication date: Available online 11 November 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Renan Campos Chisté, Daniela Ribeiro, Marisa Freitas, Andreia Leite, Tânia Moniz, Maria Rangel, Eduarda Fernandes
      Ligands of the 3-hydroxy-4-pyridinone (3,4-HPO) type, with one (mpp) or two methyl groups (dmpp), have been reported to possess biomedical, chemical and analytical applications. In this first screening study aiming to uncover new promising agents to mitigate the oxidative damage highly present in several metabolic disorders, such as diabetes mellitus, we assessed the potential of twelve 3,4-HPO metal ion complexes to modulate oxidative burst in human neutrophils. Metal ion 3,4-HPO complexes of Ni, Fe, V, Co, Cu and Zn were synthesized and tested up to 15μM. Among all the compounds, [Cu(mpp)2] and [Cu(dmpp)2] exhibited the highest scavenging capacity against superoxide radical (O2 •−) (IC50 =0.36±0.07 and 0.30±0.06μM, respectively) and against hypochlorous acid (HOCl) (IC50 =0.6±0.3 and 0.4±0.1μM, respectively). In the particular case of O2 •−, [Fe(mpp)3] and [Fe(dmpp)3] (both at 15μM) presented 35% and 22% of inhibition, respectively, while all the other compounds were neither able to scavenge O2 •− nor stimulate its production. Regarding the scavenging capacity against hydrogen peroxide (H2O2), all the compounds showed low efficiency (from 6 to 39%). Finally, with exception of [VO(mpp)2] and [VO(dmpp)2], all compounds exhibited scavenging activity against HOCl (39–81%) and the most efficient compounds were Cu(II) and Zn(II) complexes. Thus, these preliminary results uncover promising new metal ion complexes, inhibitors of neutrophil's oxidative burst, with potential anti-inflammatory properties, which may be seen as useful strategy for further studies in the treatment of a number of diseases where oxidative damage is a serious issue.
      Graphical abstract image

      PubDate: 2015-11-11T16:47:44Z
       
 
 
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