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  Subjects -> CHEMISTRY (Total: 836 journals)
    - ANALYTICAL CHEMISTRY (47 journals)
    - CHEMISTRY (586 journals)
    - CRYSTALLOGRAPHY (22 journals)
    - ELECTROCHEMISTRY (26 journals)
    - INORGANIC CHEMISTRY (41 journals)
    - ORGANIC CHEMISTRY (46 journals)
    - PHYSICAL CHEMISTRY (68 journals)

INORGANIC CHEMISTRY (41 journals)

Acta Polymerica     Hybrid Journal   (Followers: 6)
Additives for Polymers     Full-text available via subscription   (Followers: 20)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 4)
Advances in Polymer Technology     Hybrid Journal   (Followers: 11)
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: 7)
European Polymer Journal     Hybrid Journal   (Followers: 43)
Heterocyclic Communications     Hybrid Journal   (Followers: 1)
High Performance Polymers     Hybrid Journal  
Indian Journal of Chemistry - Section A     Open Access   (Followers: 5)
Inorganic Chemistry     Full-text available via subscription   (Followers: 20)
Inorganic Chemistry Communications     Hybrid Journal   (Followers: 7)
Inorganic Chemistry Frontiers     Full-text available via subscription   (Followers: 1)
Inorganic Materials     Hybrid Journal   (Followers: 2)
Inorganic Materials: Applied Research     Hybrid Journal   (Followers: 1)
Inorganica Chimica Acta     Hybrid Journal   (Followers: 3)
Inorganics     Open Access  
International Journal of Inorganic Chemistry     Open Access   (Followers: 1)
JBIC Journal of Biological Inorganic Chemistry     Hybrid Journal   (Followers: 3)
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: 1)
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: 9)
Metallodrugs     Open Access  
Open Journal of Inorganic Chemistry     Open Access   (Followers: 2)
Plasmas and Polymers     Hybrid Journal  
Polymer Bulletin     Hybrid Journal   (Followers: 7)
Polymer Composites     Hybrid Journal   (Followers: 10)
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  [2812 journals]
  • Improved syntheses of β-octabromo-meso-triarylcorrole derivatives
    • Abstract: Publication date: Available online 26 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Jan Capar, Steffen Berg, Kolle E. Thomas, Christine M. Beavers, Kevin J. Gagnon, Abhik Ghosh
      In spite of significant applications as starting materials for a variety of metallocorrole derivatives, free-base β-octabromo-meso-triarylcorroles continue to be viewed as inaccessible. The reasons range from the need for tedious column-chromatographic purification to limitations of the reductive demetallation protocol for selected systems. Here we report that column chromatography may be entirely avoided for a number of β-octabromo-meso-tris(p-X-phenyl)corrole derivatives, where X=CF3, NO2, F, H, CH3, and OCH3; instead, analytically pure products may be obtained by recrystallization from chloroform/methanol. In addition, we have presented an optimized synthesis of the heretofore inaccessible, sterically hindered ligand β-octabromo-meso-tris(2,6-dichlorophenyl)corrole, H3[Br8TDCPC], via reductive demetallation of the corresponding Mn(III) complex. With our earlier report of tris(pentafluorophenyl)corrole, H3[Br8TPFPC], a comprehensive set of optimized synthetic protocols are thus in place for a good number of β-octabromo-meso-triarylcorrole ligands. Furthermore, we have illustrated the use of these ligands by synthesizing the iron complexes Fe[Br8TDCPC]Cl and Fe[Br8TDCPC](py)2, of which the latter lent itself to single-crystal X-ray structure determination.
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      PubDate: 2015-07-28T10:30:43Z
       
  • Metal coordination and tyrosinase inhibition studies with
           Kojic-βAla-Kojic
    • Abstract: Publication date: Available online 26 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Joanna Izabela Lachowicz, Valeria Marina Nurchi, Guido Crisponi, Maria de Guadalupe Jaraquemada Pelaez, Antonio Rescigno, Piotr Stefanowicz, Marta Cal, Zbigniew Szewczuk
      Kojic acid is a natural antifungal and antibacterial agent that has been extensively studied for its tyrosinase inhibitory and metal coordination properties. Tyrosinase is a metalloenzyme with two copper ions in the active site. It is widely accepted that the tyrosinase inhibitory activity of kojic acid is related to its ability to coordinate metals. Over the past five years, we have used kojic acid to synthesize new and efficient bis-kojic acid chelators of iron and aluminium. In parallel, we investigated whether the de novo designed ligands could interfere with proper tyrosinase functioning. The present study combines our experience with inhibition and coordination studies of the new ligand: Kojic-βAla-Kojic. Research aimed at the assembly of a new potent tyrosinase inhibitor was based on the well-known crystal structure of the enzyme. Two questions were whether two kojic acids could act better than one and to what extent the length and kind of linker could ameliorate metal coordination, and inhibitory activity. Our results show that Kojic-βAla-Kojic has high affinity for Fe(III), Al(III), Zn(II), Cu(II) and strong tyrosinase inhibitory effect and it can be proposed for use in industrial and pharmaceutical applications.
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      PubDate: 2015-07-28T10:30:43Z
       
  • Effects of antitumor derivatives of ineffective transplatin on bacterial
           cells: Is DNA a pharmacological target'
    • Abstract: Publication date: Available online 20 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Jana Kasparkova, Viktor Brabec
      The effects of the two representatives of the antitumor transplatinum agents, trans-[PtCl2(methylamine)2] and trans-[PtCl2(NH3)(1-methyl-7-azaindole)] on bacterial growth were examined. The results show that these antitumor transplatinum agents can be grouped with the coordination Pt(II) compounds exhibiting antitumor activity and capable of inducing bacterial filamentation and initiate lysis in lysogenic bacteria. The results corroborate the thesis that DNA is the potential cellular target also for a class of antitumor derivatives of transplatin.
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      PubDate: 2015-07-24T10:18:51Z
       
  • Progressive inflammatory pathology in the retina of aluminum-fed 5xFAD
           transgenic mice
    • Abstract: Publication date: Available online 20 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Pogue AI, Dua P, Hill JM, Lukiw WJ
      At least 57 murine transgenic models for Alzheimer's disease (Tg-AD) have been developed to overexpress the 42 amino acid amyloid-beta (Aβ42) peptide in the central nervous system (CNS). These ‘humanized murine Tg-AD models’ have greatly expanded our understanding of the contribution of Aβ42 peptide-mediated pro-inflammatory neuropathology to the AD process. A number of independent laboratories using different amyloid-overexpressing Tg-AD models have shown that supplementation of murine Tg-AD diets and/or drinking water with aluminum significantly enhances Aβ42 peptide-mediated inflammatory pathology and AD-type cognitive change compared to animals receiving control diets. In humans AD-type pathology appears to originate in the limbic system and progressively spreads into primary processing and sensory regions such as the retina. In these studies, for the first time, we assess the propagation of Aβ42 and inflammatory signals into the retina of 5xFAD Tg-AD amyloid-overexpressing mice whose diets were supplemented with aluminum. The two most interesting findings were (1) that similar to other Tg-AD models, there was a significantly accelerated development of Aβ42 and inflammatory pathology in 5xFAD Tg-AD mice fed aluminum; and (2) in aluminum-supplemented animals, markers for inflammatory pathology appeared in both the brain and the retina as evidenced by an evolving presence of Aβ42 peptides, and accompanied by inflammatory markers — cyclooxygenase-2 (COX-2) and C-reactive protein (CRP). The results indicate that in the 5xFAD Tg-AD model aluminum not only enhances an Aβ42-mediated inflammatory degeneration of the brain but also appears to induce AD-type pathology in an anatomically-linked primary sensory area that involves vision.
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      PubDate: 2015-07-24T10:18:51Z
       
  • Increasing DNA reactivity and in vitro antitumor activity of trans
           diiodido Pt(II) complexes with UVA light
    • Abstract: Publication date: Available online 21 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Francisco Navas, Stefanie Perfahl, Claudio Garino, Luca Salassa, Olga Novakova, Carmen Navarro, Patrick J. Bednarski, Jaroslav Malina, Adoración.G. Quiroga
      trans Diiodido platinum(II) complexes bearing the same as well as different aliphatic amines (mixed-amines) are interesting compounds; cytotoxicity and interactions with some important biological models have already been demonstrated. Herein we described the interaction of such compounds with ct-DNA, supercoiled and linearized plasmid DNA and 5-GMP. Interestingly, UV irradiation of these compounds results in an increase in reactivity towards DNA in such model systems. Additionally, the cytotoxicity of the trans-Pt(II) complexes towards human cancer cells is noticeably increased when treatment is combined with UVA-irradiation. Therefore, with this work we have demonstrated that trans diiodido compounds can be activated by UV-light over short treatment times.
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      PubDate: 2015-07-24T10:18:51Z
       
  • Oxidative DNA Cleavage by Cu(II) Complexes: Effect of Periphery
           Substituent Groups
    • Abstract: Publication date: Available online 20 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Wei Wang, Young Ae Lee, Gyeongwon Kim, Seog K. Kim, Ga Ye Lee, Jinheung Kim, Youngmee Kim, Gyeong Jin Park, Cheal Kim
      A series of structurally-related [Cu(R-benzyl-dipicolylamine)(NO3)2] complexes, where R=methoxy- (1), methyl- (2), H- (3), fluoro- (4), and nitro-group (5), were synthesized, and their activity on DNA cleavage was investigated by linear dichroism (LD) and electrophoresis. The addition of a benzyl group to the dipicolylamine ligand of the [Cu(dipicolylamine)(NO3)2] complex (A), i.e., the [Cu(benzyl-dipicolylamine)(NO3)2] complex (3), caused significant enhancement in the efficiency of oxidative cleavage of both super-coiled (sc) and double stranded (ds) DNA, as evidenced by the electrophoresis pattern and faster decrease in the LD intensity at 260nm. The efficiency in DNA cleavage was also altered with further modifications of the benzyl group by the introduction of various substituents at the para-position. The cleavage efficiency appeared to be the largest when the methyl group was attached. The order of efficiency in DNA cleavage was methyl>methoxy≈H>fluoro≈nitro group. When an electron-withdrawing group was introduced, the cleavage efficiency decreased remarkably. The reactive oxygen species involved in the cleavage process were the superoxide radical and singlet oxygen. A possible mechanism for this variation in the DNA cleavage efficiency was proposed.
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      PubDate: 2015-07-24T10:18:51Z
       
  • The Reaction of a Platinated Methionine Motif of CTR1 with Cysteine and
           Histidine Is Dependent upon the Type of Precursor Platinum Complex
    • Abstract: Publication date: Available online 21 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Guolin Ma, Qin Wu, Xuelei Wu, Fabio Arnesano, Giovanni Natile, Einar Sletten, Yangzhong Liu
      The human copper protein (hCTR1) is believed to facilitate the cellular uptake of cisplatin. Cisplatin likely binds to the Methionine (Met)-rich motifs located in the N-terminus of hCTR1, and ligand exchange would be essential if cisplatin has to pass through the hCTR1 channel. In this work, we investigated the reaction between platinated adducts of a methionine-rich motif of yeast CTR1 (Mets7) and N-acetyl-cysteine (AcCys) or N-acetyl-histidine (AcHis), mimicking metal-binding residues downstream the CTR1 channel. Platination involved two cis-compounds, cisplatin and oxaliplatin, and one monofunctional complex, cis-diammine(pyridine)chloridoplatinum(II) (cDPCP). The reactions were monitored by HPLC and the products were characterized by ESI-MS. The results indicate different reactivity depending upon the platinum complex. The cisplatin/Mets7 adduct reacts readily with both cysteine and histidine (t1/2 <2min). In contrast, the oxaliplatin/Mets7 adduct reacts with cysteine but not with histidine, whereas cDPCP/Mets7 adduct reacts with histidine but not with cysteine. Hence, Mets7 adducts of these platinum complexes exhibit different reactivity towards downstream coordinating amino acids. These results suggest that each platinum complex possesses different reactivity and consequently may lead to differences in their cellular distribution and bioactivity.
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      PubDate: 2015-07-24T10:18:51Z
       
  • Highly delayed systemic translocation of aluminium-based adjuvant in CD1
           mice following intramuscular injections
    • Abstract: Publication date: Available online 22 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Guillemette Crépeaux, Housam Eidi, Marie-Odile David, Eleni Tzavara, Bruno Giros, Christopher Exley, Patrick A. Curmi, Christopher A. Shaw, Romain K. Gherardi, Josette Cadusseau
      Concerns regarding vaccine safety have emerged following reports of potential adverse events in both humans and animals. In the present study, alum, alum-containing vaccine and alum adjuvant tagged with fluorescent nanodiamonds were used to evaluate i) the persistence time at the injection site, ii) translocation of alum from the injection site to lymphoid organs, iii) behaviour of adult CD1 mice following intramuscular injection of alum (400μg Al/kg). Results showed for the first time a strikingly delayed systemic translocation of adjuvant particles. Alum-induced granuloma remained for a very long time in the injected muscle despite progressive shrinkage from day 45 to day 270. Concomitantly, a markedly delayed translocation of alum to the draining lymph nodes, major at day 270 endpoint, was observed. Translocation to the spleen was similarly delayed (highest number of particles at day 270). In contrast to C57BL/6J mice, no brain translocation of alum was observed by day 270 in CD1 mice. Consistently neither increase of Al cerebral content, nor behavioural changes were observed. On the basis of previous reports showing alum neurotoxic effects in CD1 mice, an additional experiment was done, and showed early brain translocation at day 45 of alum injected subcutaneously at 200μg Al/kg. This study confirms the striking biopersistence of alum. It points out an unexpectedly delayed diffusion of the adjuvant in lymph nodes and spleen of CD1 mice, and suggests the importance of mouse strain, route of administration, and doses, for futures studies focusing on the potential toxic effects of aluminium-based adjuvants.
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      PubDate: 2015-07-24T10:18:51Z
       
  • Interactions of Carboplatin and Oxaliplatin with Proteins: Insights from
           X-ray structures and mass spectrometry studies of their Ribonuclease A
           adducts
    • Abstract: Publication date: Available online 21 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Luigi Messori, Tiziano Marzo, Antonello Merlino
      Oxaliplatin and carboplatin are two platinum(II) drugs in widespread clinical use for the treatment of various types of cancers; yet, structural information on their interactions with proteins is scarce. Here, the X-ray structures of the adducts formed upon reaction of carboplatin and oxaliplatin with bovine pancreatic ribonuclease (RNase A) are reported and compared with results obtained for the structure of the RNase A-cisplatin adduct derived from isomorphous crystals, under the same experimental conditions. Additional details on the binding mode of these metallodrugs toward RNase A are provided by Electrospray Ionisation Mass Spectrometry (ESI MS) measurements, thus offering insight on the occurring metal-protein interactions. Notably, while carboplatin and cisplatin mainly bind the side chain of Met29, oxaliplatin also binds the side chains of Asp14, of catalytically important His119 and, to a lesser extent, of His105. On the basis of the available data, a likely mechanism for oxaliplatin hydrolysis and binding to the protein is proposed. These results are potentially useful for a better understanding of the biological chemistry, toxicity and side effects of this important class of antitumor agents.
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      PubDate: 2015-07-24T10:18:51Z
       
  • Cytotoxicity of Ru(II) piano-stool complexes with chloroquine and
           chelating ligands against breast and lung tumor cells: Interactions with
           DNA and BSA
    • Abstract: Publication date: Available online 23 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Legna Colina-Vegas, Wilmer Villarreal, Maribel Navarro, Clayton Rodrigues de Oliveira, Angélica E. Graminha, Pedro Ivo da S. Maia, Victor M. Deflon, Antonio G. Ferreira, Marcia Regina Cominetti, Alzir A. Batista
      The synthesis and spectroscopic characterization of nine π-arene piano-stool ruthenium (II) complexes with aromatic dinitrogen chelating ligands or containing chloroquine (CQ), are described in this study: [Ru(η6-C10H14)(phen)Cl]PF6 (1), [Ru(η6-C10H14)(dphphen)Cl]PF6 (2), [Ru(η6-C10H14)(bipy)Cl]PF6 (3), [Ru(η6-C10H14)(dmebipy)Cl]PF6 (4) and [Ru(η6-C10H14)(bdutbipy)Cl]PF6 (5), [Ru(η6-C10H14)(phen)CQ](PF6)2 (6), [Ru(η6-C10H14)(dphphen)CQ](PF6)2 (7), [Ru(η6-C10H14)(bipy)CQ](PF6)2 (8), [Ru(η6-C10H14)(dmebipy)CQ](PF6)2 (9): [1,10-phenanthroline (phen), 4,7-diphenyl-1,10-phenanthroline (dphphen), 2,2’-bipyridine (bipy), 5,5’-dimethyl-2,2’-bipyridine (dmebipy), 4,4’-di-t-buthyl-2,2’-bipyridine (dbutbipy)] The solid state structures of five ruthenium complexes (1-5) were determined by X-ray crystallography. Electrochemical experiments were performed by cyclic voltammetry to estimate the redox potential of the RuII/RuIII couple in each case. Their interactions with DNA and BSA, and activity against four cell lines (L929, A549, MDA-MB-231 and MCF-7) were evaluated. Compounds 2, 6 through 9, interact with DNA was comparable to the one observed for free chloroquine. The results of fluorescence titration revealed that these complexes strongly quenched the intrinsic fluorescence of BSA following a static quenching procedure. Binding constants (K b) and the number of binding sites (n~1) were calculated using modified Stern–Volmer equations. The thermodynamic parameters ΔG at different temperatures were calculated and subsequently the values of ΔH and ΔS were also calculated, which revealed that hydrophobic and electrostatic interactions play a major role in the BSA–complex association. The MTT assays results indicated that complexes 2, 5 and 7 showed cytostatic effects at appreciably lower concentrations than those needed for cisplatin, chloroquine and doxorubicin.
      Graphical abstract image

      PubDate: 2015-07-24T10:18:51Z
       
  • Synthesis, characterization and anti-diabetic therapeutic potential of
           novel aminophenol-derivatized nitrilotriacetic acid vanadyl complexes
    • Abstract: Publication date: Available online 23 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Na Wang, Ziwei Wang, Xia Niu, Xiaoda Yang
      In the present work, we synthesised three novel aminophenol-derivatized nitrilotriacetic acid vanadyl complexes (VOohpada,VOmhpada,VOphpada) using the strategy of rational incorporation of antioxidant groups in ligand in order to balance the side effects with the therapeutic properties. The complexes were characterized by IR, UV–VIS, ESI-MS and elemental analysis. The biological evaluations in vitro revealed that the position of the hydroxyl group of aminophenol moiety regulated the antioxidant activity of the complexes as well as the cytotoxicity on HK-2 cells. The vanadyl complex of p-hydroxyl aminophenol derivative (VOphpada) exhibited better antioxidant activity and lower cytotoxicity than other analogs. In type II diabetic db/db mice, VOphpada (0.1mmol/kg/day) effectively reduced blood glucose level, improved glucose tolerance, and alleviated stresses induced by hyperglycemia and hyperlipidemia. VOphpada treatment significantly increased expression of PPARα and γ, activated Akt, and inactivated JNK in muscle and adipose tissues. The insulin enhancement effects of VOphpada were observed more potent than BMOV. Moreover, VOphpada decreased the level of kidney injury molecule-1 marker (KIM-1), suggesting a potentially lower renal toxicity. In overall, the present results suggest VOphpada as a novel hypoglycemic agent with improved efficacy-over-toxicity index.
      Graphical abstract image

      PubDate: 2015-07-24T10:18:51Z
       
  • The Crystal Structure of Heme Acquisition System A from Yersinia
           pseudotuberculosis (HasAypt): Roles of the Axial Ligand Tyr75 and Two
           Distal Arginines in Heme Binding
    • Abstract: Publication date: Available online 18 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Masahiro Kanadani, Takehiro Sato, Tomoya Hino, Shingo Nagano, Shin-ichi Ozaki
      Some Gram-negative pathogens utilize an extracellular heme-binding protein called hemophore to satisfy their needs for iron, a metal element essential for most living things. We report here crystal structures of heme acquisition system A from Yersinia pseudotuberculosis (HasAypt) and its Y75A mutant. The wild-type HasAypt structure revealed that the heme iron is coordinated with Tyr75 and a water molecule. The heme-bound water molecule makes extensive hydrogen bond network that includes Arg40 and Arg144 on the distal heme pocket. Arg40, highly conserved for HasAs from Yersinia species, forms a salt bridge with the propionate side chain of heme, and makes π−π stacking and hydrophobic interactions with porphyrin plane. Interestingly, similar Arg-heme interactions are also found for periplasmic heme transporter, PhuT, suggesting that this is an example of a convergent evolution and one of the important interactions for bacterial heme transportation. Heme titration, heme binding kinetics, and the crystal structures of wild-type and Y75A proteins show that, although Tyr75 is primarily important for heme capturing, other interactions with Arg40, Arg144, and hydrophobic residues also contribute for heme acquisition. We also found that HasAypt can form a dimer in solution. The structure of the domain-swapped Y75A HasAypt dimer shows the presence of two low-spin heme molecules coordinated with His84 and His140, and displacement of the Arg40 loop of dimeric Y75A HasAypt results in deformation of the heme-binding pocket. A similar rearrangement of the distal heme loop might occur in heme transfer from HasAypt to HasRypt.
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      PubDate: 2015-07-19T21:38:53Z
       
  • Metal complexes of 6-pyrazolylpurine derivatives as models for
           metal-mediated base pairs
    • Abstract: Publication date: Available online 15 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Indranil Sinha, Alexander Hepp, Jutta Kösters, Jens Müller
      6-(3,5-Dimethylpyrazol-1-yl)purine has recently been introduced as an artificial nucleobase for the specific recognition of canonical nucleobases via the formation of a metal-mediated base pair. We report here the synthesis and structural characterization by single crystal X-ray diffraction analysis of a series of metal complexes of the corresponding alkylated model nucleobases 9-methyl-6-(3,5-dimethylpyrazol-1-yl)purine 2 and 9-methyl-6-pyrazol-1-yl-purine 7. The sterically more demanding ligand 2 forms the Cu2+ complexes [Cu(2)(NO3)2] and [Cu(2)Cl2] with a 1:1 stoichiometry of ligand and metal ion. In contrast, ligand 7 forms complexes [Cu(7)2(NO3)](NO3) and [Ag(7)2](ClO4) with a 2:1 stoichiometry. The molecular structures of [Cu(2)(NO3)2] and [Cu(2)Cl2] confirm the previously suggested coordination pattern, i.e. Cu2+ is coordinated via the pyrazole nitrogen atom and the purine N7 position. The fact that different relative orientations of the two ligands in [Cu(7)2(NO3)](NO3) and [Ag(7)2](ClO4) are observed allows the prediction that the corresponding metal-mediated homo base pairs should be stable both in regular antiparallel-stranded and in the rare parallel-stranded double helices.
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      PubDate: 2015-07-16T21:33:59Z
       
  • The Homopentameric Chlorite Dismutase from Magnetospirillum sp.
    • Abstract: Publication date: Available online 15 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Diana M. Freire, Maria G. Rivas, André M. Dias, Ana T. Lopes, Cristina Costa, Teresa Santos-Silva, Sabine Van Doorslaer, Pablo J. González
      Chlorite dismutase (Cld) is a b-type heme containing enzyme that catalyzes the reduction of chlorite into chloride plus dioxygen. This enzyme has gained attention because it can be used in the development of bioremediation processes, biosensors, and controlled dioxygen production. In the present work, Cld was purified from Magnetospirillum sp. cells cultured anaerobically with acetate/perchlorate until stationary phase. Biochemical, spectroscopic and X-ray crystallography methods showed that Cld from Magnetospirillum sp. is a ~140kDa homopentamer comprising ~27.8kDa monomers. Preliminary X-ray crystallography studies confirmed the quaternary structure and the presence of one b-type heme per monomer. The EPR spectroscopic signature of the as-purified Cld samples is affected by the buffer composition used during the purification. Potassium phosphate buffer is the only buffer that affected neither the spectral nor the kinetic properties of Cld. Kinetic studies in solution revealed that Cld from Magnetospirillum sp. decomposes chlorite at high turnover rates with optimal pH6.0. A temperature below 10°C is required to avoid enzyme inactivation due to cofactor bleaching during turnover, and to achieve full substrate consumption. Cld kinetic parameters were not affected when kinetic assays were performed in presence of air or under argon atmosphere, but chloride is a weak mixed inhibitor that modifies the EPR signal of as-prepared samples.
      Graphical abstract image

      PubDate: 2015-07-16T21:33:59Z
       
  • Guanine Nucleobase Adducts Formed by a Monofunctional Complex:
           [Pt(N-(6-methyl-2-picolyl)-N-(2-picolyl)amine)Cl]Cl
    • Abstract: Publication date: Available online 15 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Chase Andrepont, Patricia A. Marzilli, Svetlana Pakhomova, Luigi G. Marzilli
      Monofunctional Pt(II) complexes bind to G residues in DNA and, if the carrier ligands are bulky, cause DNA structural distortions that lead to anticancer activity. We assessed the steric effects of the tridentate carrier ligand, N(H)6-Medpa (N-(6-methyl-2-picolyl)-N-(2-picolyl)amine), bearing a 6-methyl group and a 6′-proton projecting toward the nucleobase in Pt(N(H)6-Medpa)G adducts (G = 9-ethylguanine, 3′-GMP, 5′-GMP, 5′-GTP). Pt(N(H)6-Medpa)G adducts form syn and anti rotamers with the guanine O6 and the central N–H of N(H)6-Medpa on the same or opposite side of the coordination plane, respectively. Pt(N(H)6-Medpa)G adducts have some properties (ease of rotamer interchange and extent of conversion to bis adducts, Pt(N(H)6-Medpa)G 2) intermediate to properties reported for analogues having a tridentate ligand with zero or two methyl groups. However, in comparison, the syn rotamer of Pt(N(H)6-Medpa)G adducts have an unexpectedly high abundance. This result is attributable to guanine base canting, such that the 6-membered guanine ring is positioned away from the bulky 6-Me group. This canting both relieves electrostatic repulsion between the partially positive H6′ and the guanine H8 protons and creates a favorable electrostatic attraction between the H6′ proton and the partially negative guanine O6. This combined information provides insight useful for designing monofunctional anticancer agents.
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      PubDate: 2015-07-16T21:33:59Z
       
  • Phenylthiourea alters toxicity of mercury compounds in zebrafish larvae
    • Abstract: Publication date: Available online 14 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Tracy C. MacDonald, Susan Nehzati, Nicole J. Sylvain, Ashley K. James, Malgorzata Korbas, Sally Caine, Ingrid J. Pickering, Graham N. George, Patrick H. Krone
      In recent years larval stage zebrafish have been emerging as a standard vertebrate model in a number of fields, ranging from developmental biology to pharmacology and toxicology. The tyrosinase inhibitor 1-phenyl-2-thiourea (PTU) is used very widely with larval zebrafish to generate essentially transparent organisms through inhibition of melanogenesis, which has enabled many elegant studies in areas ranging from neurological development to cancer research. Here we show that PTU can have dramatic synergistic and antagonistic effects on the chemical toxicology of different mercury compounds. Our results indicate that extreme caution should be used when employing PTU in toxicological studies, particularly when studying toxic metal ions.
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      PubDate: 2015-07-16T21:33:59Z
       
  • Low Frequency Dynamics of the Nitrogenase MoFe Protein via Femtosecond
           Pump Probe Spectroscopy – Observation of a Candidate Promoting
           Vibration
    • Abstract: Publication date: Available online 14 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Margherita Maiuri, Ines Delfino, Giulio Cerullo, Cristian Manzoni, Vladimir Pelmenschikov, Yisong Guo, Hongxin Wang, Leland Gee, Christie H. Dapper, William E. Newton, Stephen P. Cramer
      We have used femtosecond pump-probe spectroscopy (FPPS) to study the FeMo-cofactor within the nitrogenase (N2ase) MoFe protein from Azotobacter vinelandii. A sub-20-fs visible laser pulse was used to pump the sample to an excited electronic state, and a second sub-10-fs pulse was used to probe changes in transmission as a function of probe wavelength and delay time. The excited protein relaxes to the ground state with a ~1.2ps time constant. With the short laser pulse we coherently excited the vibrational modes associated with the FeMo-cofactor active site, which are then observed in the time domain. Superimposed on the relaxation dynamics, we distinguished a variety of oscillation frequencies with the strongest band peaks at ~84, 116, 189, and 226cm−1. Comparison with data from nuclear resonance vibrational spectroscopy (NRVS) shows that the latter pair of signals comes predominantly from the FeMo-cofactor. The frequencies obtained from the FPPS experiment were interpreted with normal mode calculations using both an empirical force field (EFF) and density functional theory (DFT). The FPPS data were also compared with the first reported resonance Raman (RR) spectrum of the N2ase MoFe protein. This approach allows us to outline and assign vibrational modes having relevance to the catalytic activity of N2ase. In particular, the 226cm−1 is assigned as a potential ‘promoting vibration’ in the H-atom transfer (or proton-coupled electron transfer) processes that are an essential feature of N2ase catalysis. The results demonstrate that high-quality room-temperature solution data can be obtained on the MoFe protein by the FPPS technique and that these data provide added insight to the motions and possible operation of this protein and its catalytic prosthetic group.
      Graphical abstract image

      PubDate: 2015-07-16T21:33:59Z
       
  • Ru(II)-based complexes with
           N-(acyl)-N′,N′-(disubstituted)thiourea ligands: Synthesis,
           characterization, BSA- and DNA-binding studies of new cytotoxic agents
           against lung and prostate tumour cells
    • Abstract: Publication date: September 2015
      Source:Journal of Inorganic Biochemistry, Volume 150
      Author(s): Rodrigo S. Correa , Katia M. de Oliveira , Fábio G. Delolo , Anislay Alvarez , Raúl Mocelo , Ana M. Plutin , Marcia R. Cominetti , Eduardo E. Castellano , Alzir A. Batista
      Four ruthenium(II)-based complexes with N-(acyl)-N′,N′-(disubstituted)thiourea derivatives (Th) were obtained. The compounds, with the general formula trans-[Ru(PPh3)2(Th)(bipy)]PF6, interact with bovine serum albumin (BSA) and DNA. BSA-binding constants, which were in the range of 3.3–6.5×104 M−1, and the thermodynamic parameters (ΔG, ΔH and ΔS), suggest spontaneous interactions with this protein by electrostatic forces due to the positive charge of the complexes. Also, binding constant by spectrophotometric DNA titration (Kb=0.8–1.8×104 M−1) and viscosity studies indicate weak interactions between the complexes and DNA. Cytotoxicity assays against DU-145 (prostate cancer) and A549 (lung cancer) tumour cells revealed that the complexes are more active in tumour cells than in normal (L929) cells, and that they present high cytotoxicity (low IC50 values) compared with the reference metallodrug, cisplatin.
      Graphical abstract image

      PubDate: 2015-07-11T20:56:06Z
       
  • Copper(II) and nickel(II) binding sites of peptides containing adjacent
           histidyl residues
    • Abstract: Publication date: Available online 9 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Ágnes Grenács , Daniele Sanna , Imre Sóvágó
      Copper(II) and nickel(II) complexes of the terminally protected nonapeptide Ac-SGAEGHHQK-NH2 modelling the metal binding sites of the (8–16) domain of amyloid-β have been studied by potentiometric, UV–vis, CD and ESR spectroscopic methods. The studies on the mutants containing only one of the histidyl residues (Ac-SGAEGAHQK-NH2, Ac-SGAEGHAQK-NH2) have also been performed. The formation of imidazole and amide coordinated mononuclear complexes is characteristic of all systems with a preference of nickel(II) binding to the His14 site, while the involvement of both histidines in metal binding is suggested in the corresponding copper(II) complexes. The formation of bis(ligand) and dinuclear complexes has also been observed in the copper(II)-Ac-SGAEGHHQK-NH2 system. The results provide further support for the copper(II) binding ability of the (8–16) domain of amyloid-β and support the previous assumptions that via the bis(ligand) complex formation copper(II) ions may promote the formation of the oligomers of amyloid-β.
      Graphical abstract image

      PubDate: 2015-07-11T20:56:06Z
       
  • Synthesis and X-ray crystal structure of the dirhenium complex
           Re2(i-C3H7COO)4Cl2 and its interactions with the DNA purine nucleobases
    • Abstract: Publication date: Available online 9 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Alexander V. Shtemenko , Helen T. Chifotides , Dina E. Yegorova , Natalia I. Shtemenko , Kim R. Dunbar
      The dirhenium complex Re2(i-C3H7COO)4Cl2 was synthesized and characterized by X-ray crystallography, 1H NMR and electronic spectroscopies, and electrospray ionization-mass spectrometry. The reactions of Re2(i-C3H7COO)4Cl2 with the substituted DNA purine nucleobases guanine (9-methylguanine and 9-ethytlguanine) and adenine (9-methyladenine and 9-ethyladenine) were investigated by proton nuclear magnetic resonance and electronic spectroscopies as well as electrospray ionization-mass spectrometry. The data corroborate binding of two 9-methylguanine (or 9-ethytlguanine) and 9-methyladenine (or 9-ethyladenine) bases per dirhenium unit in a bidentate fashion, in equatorial positions, via sites N7/O6 and N1/N6, respectively, with concomitant substitution of two carboxylate groups to form a single isomer of cis-Re2(i-C3H7COO)2(nucleobase)2Cl2. The binding of the bases to the dirhenium core disrupts important nucleobase interactions and may have important biological implications with respect to the anticancer activity of dirhenium complexes.
      Graphical abstract image

      PubDate: 2015-07-11T20:56:06Z
       
  • Preparation, stability, and photoreactivity of thiolato ruthenium
           polypyridyl complexes: can cysteine derivatives protect ruthenium-based
           anticancer complexes'
    • Abstract: Publication date: Available online 10 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Vincent H.S. van Rixel , Anja Busemann , Adrien J. Göttle , Sylvestre Bonnet
      Ruthenium polypyridyl complexes may act as light-activatable anticancer prodrugs provided they are protected by well-coordinated ligands that i) prevent coordination of other biomolecules to the metal center in the dark, and ii) can be removed by visible light irradiation. In this paper, the use of monodentate thiol ligands RSH as light-cleavable protecting groups for the ruthenium complex [Ru(tpy)(bpy)(OH2)](PF6)2 ([1](PF6)2; tpy=2,2’;6’,2”-terpyridine, bpy=2,2’-bypyridine), is investigated. The reaction of [1]2+ with RSH=H2Cys (L-cysteine), H2Acys (N-acetyl-L-cysteine), and HAcysMe (N-acetyl-L-cysteine methyl ester), is studied by UV-visible spectroscopy, NMR spectroscopy, and mass spectrometry. Coordination of the monodentate thiol ligands to the ruthenium complex takes place upon heating to 353K, but full conversion to the protected complex [Ru(tpy)(bpy)(SR)]PF6 is only possible when a large excess of ligand is used. Isolation and characterization of the two new thiolato complexes [Ru(tpy)(bpy)(κS-HCys)]PF6 ([2]PF6) and [Ru(tpy)(bpy)(κS-HAcys)]PF6 ([3]PF6) is reported. [3]PF6 shows a Metal-to-Ligand Charge-Transfer absorption band that is red shifted (λmax =492nm in water) compared to its methionine analogue [Ru(tpy)(bpy)(κS-HAmet)](Cl)2 ([5](Cl)2, λmax =452nm; HAmet=N-acetyl-methionine). In the dark the thiolate ligand coordinated to ruthenium is oxidized even by traces of oxygen, which first leads to the sulfenato, sulfinato, and disulfide ruthenium complexes, and finally to the formation of the aqua complex [1]2+. [3]PF6 showed slow photosubstitution of the thiolate ligand by water under blue light irradiation, together with faster photooxidation of the thiolate ligand compared to dark conditions. The use of thiol vs. thioether monodentate ligands is discussed for the protection of anticancer ruthenium-based prodrugs.


      PubDate: 2015-07-11T20:56:06Z
       
  • NO2−-mediated nitrosylation of ferrous microperoxidase-11
    • Abstract: Publication date: Available online 4 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Paolo Ascenzi , Diego Sbardella , Marco Fiocchetti , Roberto Santucci , Massimo Coletta
      Microperoxidase-11 (MP11) is an undecapeptide derived from horse heart cytochrome c (cyt c) and characterized by a covalently-linked solvent-exposed heme group. Here, kinetics of the NO2 −-mediated nitrosylation of ferrous MP11 (MP11-Fe(II)) is reported. Data were obtained between pH6.4 and 8.2, at 20.0°C. The NO2 −-mediated conversion of MP11-Fe(II) to MP11-Fe(II)-NO requires one proton; accordingly, values of the apparent second-order rate constant (k on) decrease by about two orders of magnitude from (2.9±0.3)×101 M−1 s−1 to (5.0±0.6)×10−1 M−1 s−1 upon increasing pH from 6.4 to pH8.2. The slope of the linear fitting of Logk on versus pH is −1.00±0.06. Values of k on for the NO2 −-mediated nitrosylation of MP11-Fe(II) are similar to those of penta-coordinated cardiolipin-bound horse heart cyt c, exceeding by about two orders of magnitude those of wild-type cyt c. Present results highlight the role of heme distal residues in modulating horse heart cyt c reactivity.
      Graphical abstract image

      PubDate: 2015-07-06T20:34:44Z
       
  • Copper(II) complexes of terminally free alloferon peptide mutants
           containing two different histidyl (H1 and H6 or H9 or H12) binding sites
           Structure Stability and Biological Activity
    • Abstract: Publication date: Available online 3 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Agnieszka Matusiak , Mariola Kuczer , Elżbieta Czarniewska , Arkadiusz Urbański , Grzegorz Rosiński , Teresa Kowalik-Jankowska
      Mono- and dinuclear copper(II) complexes of the alloferon 1 with point mutations H9A/H12A H1GVSGH6GQA9GVA12G, H6A/H12A H1GVSGA6GQH9GVA12G and H6A/H9A H1GVSGA6GQA9GVH12G have been studied by potentiometric, UV-visible, CD, EPR spectroscopic, and mass spectrometry (MS) methods. Complete complex speciation at metal-to-ligand molar ratios 1:1 and 2:1 was obtained. For all systems studied in the 5 – 6.5 pH range, the CuL complex dominates with 3N{NH2,NIm-H1,NIm-H6 or 9 or 12} binding site. The stability of the CuL complexes for the ligands studied varies according to the H9A/H12A>H6A/H12A>H6A/H9A series. For the dinuclear systems the amine/imidazole nitrogen donor atoms of the histidine residue H1 and the imidazole nitrogen atoms of H6 or H9 or H12 can be considered as independent metal-binding sites in the species formed. The stability of the dinuclear complexes is higher when two coordinated copper(II) ions are closer to each other. The inductions of phenoloxidase activity and apoptosis in vivo in Tenebrio molitor cells by the ligands and their copper(II) complexes at pH7.4 have been studied. The H6A/H9A, H6A/H12A peptides displayed lower hemocytotoxic activity compared to that of alloferon 1, while the H9A/H12A analogue was not active. Among the copper(II) complexes, the most active was the Cu(II)-H9A/H12A complex formed at pH7.4 with 3N{NH2,NIm-H1,NIm-H6} (CuL) and 3N{NH2,N−,NIm-H6} and/or 4N{NH2,NIm-H1,N−,NIm-H6} (CuH−1 L) binding sites. The Cu(II)-H6A/H9A and Cu(II)-H6A/H12A complexes were not active.
      Graphical abstract image

      PubDate: 2015-07-06T20:34:44Z
       
  • Electrogenerated Chemiluminescence Reactions between the [Ru(bpy)3]2+
           Complex and PAMAM GX.0 Dendrimers in an Aqueous Medium
    • Abstract: Publication date: Available online 4 July 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): A. Jimenez-Ruiz , E. Grueso , P. Perez-Tejeda
      Electrogenerated chemiluminescence, ECL, reactions between tris(2,2’-bipyridine)ruthenium(II), [Ru(bpy)3]2+, and PAMAM GX.0 (X=1 and 2) dendrimers in an aqueous medium were carried out at pH10 (fully deprotonated dendrimer surface). ECL was detected in the presence of GX.0 dendrimers without addition of any known coreactant. Atomic Force Microscopy, AFM, measurements for GX.0 dendrimers in the presence of the [Ru(bpy)3]2+ complex were also done. AFM images showed the existence of aggregates (pillars) of globular shape, as well as interdendrimer networks forming fibers in the x-y direction for dendrimer aqueous solutions. ECL and AFM results in cooperation suggest that the coreactant effect of the end amine groups is improved by both the dendritic branched shells and the globular z-type aggregates. The ECL efficiency trends as a function of [GX.0] (whole range) can be interpreted taking into account the coreactant effect modulated by the presence of the z and x-y type aggregates. Importantly, ECL efficiency values can be taken as a measure of the change induced on the dendrimer aggregation in aqueous solutions when their concentrations rise. Redox potentials of the [Ru(bpy)3]3+/2+ couple in the presence of the G1.0 and G2.0 dendrimers were also determined.
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      PubDate: 2015-07-06T20:34:44Z
       
  • Editorial Board
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148




      PubDate: 2015-06-24T14:30:42Z
       
  • Contents
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148




      PubDate: 2015-06-24T14:30:42Z
       
  • Preface for the JIB Special Issue for the 12th European Biological
           Inorganic Chemistry Conference (EuroBIC 12) in Zurich, Switzerland, August
           24–28, 2014
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Eva Freisinger , Roland Sigel



      PubDate: 2015-06-24T14:30:42Z
       
  • Rhenium(I) polypyridine dibenzocyclooctyne complexes as phosphorescent
           bioorthogonal probes: Synthesis, characterization, emissive behavior, and
           biolabeling properties
    • Abstract: Publication date: July 2015
      Source:Journal of Inorganic Biochemistry, Volume 148
      Author(s): Alex Wing-Tat Choi , Hua-Wei Liu , Kenneth Kam-Wing Lo
      We report the development of rhenium(I) polypyridine complexes appended with a dibenzocyclooctyne (DIBO) moiety as bioorthogonal probes for azide-modified biomolecules. Three phosphorescent rhenium(I) polypyridine DIBO complexes [Re(N^N)(CO)3(py-C6-DIBO)][CF3SO3] (py-C6-DIBO=3-(N-(6-(3,4:7,8-dibenzocyclooctyne-5-oxycarbonylamino)hexyl)aminocarbonyl)pyridine; N^N=1,10-phenanthroline (phen) (1a), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me4-phen) (2a), 4,7-diphenyl-1,10-phenanthroline (Ph2-phen) (3a)) and their DIBO-free counterparts [Re(N^N)(CO)3(py-C6-BOC)][CF3SO3] (py-C6-BOC=3-(N-(6-(tert-butoxycarbonylamino)hexyl)aminocarbonyl)pyridine; N^N=phen (1b), Me4-phen (2b), Ph2-phen (3b)) were synthesized and characterized. Upon photoexcitation, all the complexes displayed intense and long-lived yellow triplet metal-to-ligand charge-transfer (3MLCT) (dπ(Re)→π*(N^N)) emission. The DIBO complexes underwent facile reactions with benzyl azide in methanol at 298K with second-order rate constants (k 2) in the range of 0.077 to 0.091M−1 s−1. As revealed from SDS-PAGE analysis, the DIBO complexes can selectively label azide-modified proteins and the resulting bioconjugates displayed strong phosphorescence upon photoexcitation. Results of inductively coupled plasma mass spectrometry (ICP-MS) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays indicated that the DIBO complexes accumulated in Chinese Hamster Ovary (CHO) cells with considerable cytotoxic activity. Upon incubation of CHO cells with these complexes, relatively weak intracellular emission was observed. In contrast, upon pretreatment of the cells with 1,3,4,6-tetra-O-acetyl-N-azidoacetyl-d-mannosamine (Ac4ManNAz), intense emission was observed from the cell membrane and some internal compartments. The results suggest that the DIBO complexes are promising candidates for imaging azide-labeled biomolecules.
      Graphical abstract image

      PubDate: 2015-06-24T14:30:42Z
       
  • A molecular level mechanism for uranium (VI) toxicity through Ca2+
           displacement in pyrroloquinoline quinone-dependent bacterial dehydrogenase
           
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Katherine A. Burbank , Robert A. Walker , Brent M. Peyton
      Dipicolinic acid (DPA), a small molecule analogue for the pyrroloquinoline quinone (PQQ) bacterial dehydrogenase cofactor, was used to model displacement of the complexing ion, Ca2+, by a uranium (VI) dioxo-cation, UO2 2+ . Complexation of UO2 2+ with DPA through the displacement of Ca2+ was examined with UV/visible spectroscopy, ESI (electrospray ionization)-Mass spectrometry, and density functional theory based-modeling. The UO2 2+ displacement of other biologically important metal cations (Zn2+, Cu2+, Ni2+, and Fe3+) from DPA was also examined. Results show that UO2 2+ has a distinctly higher binding affinity (logβ=10.2±0.1) for DPA compared to that of Ca2+ (logβ=4.6±0.1), and provide molecular level insight into the mechanism of uranium toxicity associated with the {ONO} site. These results support those of VanEngelen et al. (2011) where a key interaction between PQQ and UO2 2+ produced significant uranium toxicity in bacteria. The observed toxicity mechanism was determined to be the displacement of a Ca2+ cation bound to the {ONO} site on PQQ and was observed even at submicromolar UO2 2+ concentrations. Here we couple experimental findings with density functional theory (DFT) calculations to investigate the electronic and structural properties that make the {ONO} site so distinctively favorable for UO2 2+ binding. This novel approach using integrated experimental and fundamental atomic based models opens the path to identify a library of potential uranium interactions with critical biological molecules.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Editorial Board
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149




      PubDate: 2015-06-11T17:30:20Z
       
  • Contents
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149




      PubDate: 2015-06-11T17:30:20Z
       
  • Metals in the active site of native protein phosphatase-1
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Ewald Heroes , Jens Rip , Monique Beullens , Luc Van Meervelt , Stefan De Gendt , Mathieu Bollen
      Protein phosphatase-1 (PP1) is a major protein Ser/Thr phosphatase in eukaryotic cells. Its activity depends on two metal ions in the catalytic site, which were identified as manganese in the bacterially expressed phosphatase. However, the identity of the metal ions in native PP1 is unknown. In this study, total reflection X-ray fluorescence (TXRF) was used to detect iron and zinc in PP1 that was purified from rabbit skeletal muscle. Metal exchange experiments confirmed that the distinct substrate specificity of recombinant and native PP1 is determined by the nature of their associated metals. We also found that the iron level associated with native PP1 is decreased by incubation with inhibitor-2, consistent with a function of inhibitor-2 as a PP1 chaperone.
      Graphical abstract image

      PubDate: 2015-06-11T17:30:20Z
       
  • Copper(II) complexes with the non-steroidal anti-inflammatory drug
           tolfenamic acid: Structure and biological features
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Alketa Tarushi , Spyros Perontsis , Antonios G. Hatzidimitriou , Athanasios N. Papadopoulos , Dimitris P. Kessissoglou , George Psomas
      Copper(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid (Htolf) with the oxygen-donor ligands methanol (MeOH) or N,N-dimethylformamide (DMF) and/or the nitrogen-donor heterocyclic ligands 2,2′-bipyridine (bipy), 2,2′-bipyridylamine (bipyam), 1,10-phenanthroline (phen) or pyridine (py) were synthesized and characterized. The crystal structures of five novel complexes were determined by X-ray crystallography where tolfenamic acid is deprotonated being in different binding modes. Equimolar quantities of CuCl2, tolf−1 and bipy led to the formation of [Cu(tolf-O,O′)(bipy)Cl] (1), while with a 1:2 Cu(II):tolf ratio, complexes [Cu(tolf-O,O′)2(bipy)] (2), [Cu(tolf-O,O′)2(bipyam)]·0.5MeOH (3 0.5MeOH), [Cu(tolf-O,O′)(tolf-O)(phen)(MeOH)] (4) and [Cu(tolf-O)2(py)2(MeOH)2] (5) were isolated. The interaction of the complexes with serum albumin proteins was studied by fluorescence spectroscopy with the determined binding constant bearing relative high values. The scavenging ability of the complexes towards 1,1-diphenyl-picrylhydrazyl, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals was investigated and the in vitro inhibitory activity against soybean lipoxygenase was evaluated and complexes 4 and 5 were the more active compounds among those tested. Spectroscopic (UV), electrochemical (cyclic voltammetry) and physicochemical (viscosity measurements) techniques were employed in order to study the binding mode and strength of the complexes to calf-thymus (CT) DNA suggesting intercalation as the most possible mode of binding. Competitive studies with ethidium bromide (EB) revealed the ability of the complexes to displace the DNA-bound EB. The biological properties of complexes 1–5 were evaluated in regard to previously reported complex [Cu2(tolf-O,O′)4(DMF)2] (6).
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      PubDate: 2015-06-11T17:30:20Z
       
  • Synthesis, crystal structure and anaerobic DNA photocleavage of ruthenium
           complexes [Ru(tpy)(dpoq)Cl]+ and [Ru(tpy)(dpoq)CH3CN]2+
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Hui-juan Yu , Shu-mei Huang , Hui Chao , Liang-nian Ji
      Two new Ru(II) complexes [Ru(tpy)(dpoq)Cl]+ 1 and [Ru(tpy)(dpoq)CH3CN]2+ 2 (tpy=2,2':6',2''-terpyridine; dpoq=dipyrido[1,2,5]oxadiazolo[3,4-b]quinoxaline) have been synthesized and characterized by elemental analysis, 1H NMR, electrospray ionization mass spectra (ESI-MS) and X-ray crystallographic study. The experimental results of spectra titration, thermal denaturation and viscosity measurements suggest that the two complexes intercalatively bind to DNA. When irradiated under light, the two complexes could efficiently photocleave DNA both under aerobic and anaerobic condition. The mechanism studies reveal that the photocleavage reaction functions through both oxygen-independent (photoinduced electron transfer, type III reaction) and oxygen-dependent (singlet oxygen generation, type II reaction) pathways and the oxygen-independent pathway is the major process. These complexes will be more promising photodynamic therapy (PDT) candidates used for treating hypoxic tumors.
      Graphical abstract image

      PubDate: 2015-06-11T17:30:20Z
       
  • A novel resting form of the trinuclear copper center in the double mutant
           of a multicopper oxidase, CueO, Cys500Ser/Glu506Ala
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Takao Kajikawa , Ryosuke Sugiyama , Kunishige Kataoka , Takeshi Sakurai
      A multicopper oxidase, CueO was doubly mutated at its type I copper ligand, Cys500 and an acidic amino acid residue located in the proton transfer pathway, Glu506, to Ser and Ala, respectively. Cys500Ser/Glu506Ala was mainly in a novel resting form to afford the absorption band at ca. 400nm and an EPR signal with a highly anisotropic character derived from type III copper. However, Cys500Ser/Glu506Ala gave the same reaction intermediate (peroxide intermediate) as that from Cys500Ser and Cys500Ser/Glu506Gln.
      Graphical abstract image

      PubDate: 2015-06-11T17:30:20Z
       
  • Cis-[RuCl(BzCN)(N–N)(P–P)]PF6 complexes: Synthesis and in
           vitro antitumor activity (BzCN=benzonitrile;
           N–N=2,2′-bipyridine; 1,10-phenanthroline;
           P–P=1,4-bis(diphenylphosphino) butane,
           1,2-bis(diphenylphosphino)ethane, or
           1,1′-(diphenylphosphino)ferrocene)
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Flávia de C. Pereira , Benedicto A.V. Lima , Aliny P. de Lima , Wanessa C. Pires , Thallita Monteiro , Lorena F. Magalhães , Wanderson Costa , Angélica E. Graminha , Alzir A. Batista , Javier Ellena , Elisângela de P. Siveira-Lacerda
      The motivation to use ruthenium complexes in cancer treatment has led our research group to synthesize complexes with this metal and test them against several types of tumor cells, yielding promising results. In this paper the results of biological tests, assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, were carried out on the complexes cis-[RuCl(BzCN)(bipy)(dppe)]PF6 (1), cis-[RuCl(BzCN)(bipy)(dppb)]PF6 (2), cis-[RuCl(BzCN)(bipy)(dppf)]PF6 (3) and cis-[RuCl(BzCN)(phen)(dppb)]PF6 (4) which are described [BzCN=benzonitrile; bipy=2,2′-bipyridine; phen=1,10-phenanthroline; dppe=1,2-bis(diphenylphosphino) ethane; dppb=1,4-bis-(diphenylphosphino)butane; dppf=1,1′-bis(diphenylphosphino)ferrocene]. The present study is focused on the cytotoxic activity of complexes (1)–(4) against four tumor cell lines and on the apoptosis and changes in the cell cycle and gene expression observed in the sarcoma 180 (S180) tumor cell line treated with complex (1). The results demonstrated that this complex inhibits S180 cell growth, with an IC50 of 17.02±8.21μM, while exhibiting lower cytotoxicity (IC50 =53.73±5.71μM) towards lymphocytes (normal cells). Flow cytometry revealed that the complex inhibits the growth of tumor cells by inducing apoptosis as evidenced by an increase in the proportion of cells positive for annexin V staining and G0/G1 phase cell-cycle arrest. Further investigation showed that complex (1) induces a drop in the mitochondrial membrane potential and provokes a decrease in Bcl-2 protein expression and increase in caspase 3 activation, while the increased activation of caspase 8 caused a decrease in the gene expression in caspases 3 and 9. Increases in Tp53 and Bax expressions were also observed.
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      PubDate: 2015-06-11T17:30:20Z
       
  • Reactions of model proteins with aurothiomalate, a clinically established
           gold(I) drug: The comparison with auranofin
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Farivash Darabi , Tiziano Marzo , Lara Massai , Federica Scaletti , Elena Michelucci , Luigi Messori
      Aurothiomalate (AuTm) is an old, clinically established, antiarthritic gold drug that is currently being reconsidered as a candidate drug for cancer treatment and for other therapeutic indications within a more general drug repositioning program. As the biological effects of gold drugs seem to be mediated, mainly, by their interactions with protein targets we have analyzed here, in detail, the metalation patterns produced by aurothiomalate in a few model proteins. In particular, the reactions of aurothiomalate with the small proteins ribonuclease A, cytochrome c and lysozyme were explored through ESI MS (electrospray ionization mass spectrometry) analysis. Notably, characteristic and rather constant features emerged in the protein metalation patterns induced by AuTm that are markedly distinct from those caused by auranofin; a non-covalent interaction mode is invoked for AuTm binding to the mentioned proteins. The affinity constants of AuTm toward the three mentioned proteins were also initially assessed. The implications of the present findings are discussed.
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      PubDate: 2015-06-11T17:30:20Z
       
  • HSA-based phosphorescent probe for two-photon in vitro visualization
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Pavel S. Chelushkin , Natalia V. Nukolova , Alexei S. Melnikov , Pavel Yu. Serdobintsev , Pavel A. Melnikov , Dmitry V. Krupenya , Igor O. Koshevoy , Sergey V. Burov , Sergey P. Tunik
      Two-photon microscopy reveals several advantages over conventional one since it provides higher spatial resolution as well as deeper penetration into the sample under study. The development of suitable two-photon probes is one of the most challenging tasks in this area. Here we present phosphorescent non-covalent adduct of human serum albumin and Au-Ag alkynyl-diphosphine complex, [Au14Ag4(C2Ph)12(PPh2C6H4PPh2)6][PF6]4, which exhibits high cross section of two-photon-induced luminescence (δ TPE) within large near-infrared excitation wavelength region (700–800nm) with maximum δ TPE about 38 GM at 740nm. This feature makes it a promising probe for multiphoton bioimaging as demonstrated by successful visualization of glioma C6 cells and various tissues by two-photon confocal microscopy both in planar and z-stacking modes. Additionally, the broad excitation region enables optimization of the signal-to-background auto-fluorescence ratio via variation of excitation wavelength.
      Graphical abstract image

      PubDate: 2015-06-11T17:30:20Z
       
  • Antitumor and antiparasitic activity of novel ruthenium compounds with
           polycyclic aromatic ligands
    • Abstract: Publication date: Available online 9 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Helena Guiset Miserachs , Micaella Cipriani , Jordi Grau , Marta Vilaseca , Julia Lorenzo , Andrea Medeiros , Marcelo A. Comini , Dinorah Gambino , Lucía Otero , Virtudes Moreno
      Five novel ruthenium(II)–arene complexes with polycyclic aromatic ligands were synthesized, comprising three compounds of the formula [RuCl(η6-p-cym)(L)][PF6], where p-cym=1-isopropyl-4-methylbenzene and L are the bidentate aromatic ligands 1,10-phenanthroline-5,6-dione, 1, 5-amine-1,10-phenanthroline, 4, or 5,6-epoxy-5,6-dihydro- phenanthroline, 5. In the other two complexes, [RuCl2(η6-p-cym)(L')], the metal is coordinated to a monodentate ligand L', where L' is phenanthridine, 2, or 9-carbonilanthracene, 3. All compounds were fully characterized by mass spectrometry and elemental analysis, as well as NMR and IR spectroscopic techniques. Obtained ruthenium compounds as well as their respective ligands were tested for their antiparasitic and antitumoral activities. Even though all compounds showed lower T. brucei activity than the free ligands, they also resulted less toxic on mammalian cells. Cytotoxicity assays on HL60 cells showed a moderate antitumoral activity for all ruthenium compounds. Compound 1 was the most potent antitumoral (IC50 =1.26±0.78μM) and antiparasitic (IC50 =0.19μM) agent, showing high selectivity towards the parasites (selectivity index>100). As complex 1 was the most promising antitumoral compound, its interaction with ubiquitin as potential target was also studied. In addition, obtained ruthenium compounds were found to bind DNA, and they are thought to interact with this macromolecule mainly through intercalation of the aromatic ligand.
      Graphical abstract image

      PubDate: 2015-06-11T17:30:20Z
       
  • Molecular mechanisms of apoptosis and cell selectivity of zinc
           dithiocarbamates functionalized with hydroxyethyl substituents
    • Abstract: Publication date: Available online 9 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Yee Seng Tan , Kah Kooi Ooi , Kok Pian Ang , Abdah Md Akim , Yoke-Kqueen Cheah , Siti Nadiah Abdul Halim , Hoi-Ling Seng , Edward R.T. Tiekink
      In the solid state each of three binuclear zinc dithiocarbamates bearing hydroxyethyl groups, {Zn[S2CN(R)CH2CH2OH]2}2 for R=iPr (1), CH2CH2OH (2), and Me (3), and an all alkyl species, [Zn(S2CNEt2)2]2 (4), features a centrosymmetric {ZnSCS}2 core with a step topology; both 1 and 3 were isolated as monohydrates. All compounds were broadly cytotoxic, specifically against human cancer cell lines compared with normal cells, with greater potency than cisplatin. Notably, some selectivity was indicated with 2 being most potent against human ovarian carcinoma cells (cisA2780), and 4 being more cytotoxic toward multidrug resistant human breast carcinoma cells (MCF-7R), human colon adenocarcinoma cells (HT-29), and human lung adenocarcinoma epithelial cells (A549). Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis in HT-29 cells is demonstrated via both extrinsic and intrinsic pathways. Compounds 2–4 activate the p53 gene while 1 activates both p53 and p73. Cell cycle arrest at the S and G2/M phases correlates with inhibition of HT-29 cell growth. Cell invasion is also inhibited by 1–4 which is correlated with down-regulation of NF-ĸB.
      Graphical abstract image

      PubDate: 2015-06-11T17:30:20Z
       
  • Synthesis, crystal structure and biological activity of two Mn complexes
           with 4-acyl pyrazolone derivatives
    • Abstract: Publication date: Available online 5 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Yue Li , Jing Zhao , Chuan-Chuan He , Li Zhang , Su-Rong Sun , Guan-Cheng Xu
      In order to study the biological activities of transitional metal complexes based on 4-acyl pyrazolone derivatives, two Mn complexes [Mn(HLa)(La)]·(CH3CN)1.5 ·H2O (1) and [Mn2(Lb)2(μ-EtO)2(EtOH)2] (2) (H2La =N-(1-phenyl-3-methyl-4-benzoyl-5-pyrazolone)-2- thiophenecarboxylic acid hydrazide, H2Lb =N-(1-phenyl-3-methyl-4-propenylidene-5-pyrazolone)- 2-thiophenecarboxylic acid hydrazide) have been synthesized and characterized. Single crystal X-ray diffraction analysis indicated that 1 is a mononuclear complex and 2 exhibits a dinuclear centrosymmetric structure. Binding of the complexes with Herring Sperm DNA (HS-DNA) were showed that complexes 1 and 2 could intercalate to DNA with quenching constant of 5.3×104 M−1 and 4.9×104 M−1, respectively. The interactions of the complexes with bovine serum albumin (BSA) indicated complexes 1 and 2 could quench the intrinsic fluorescence of BSA in a static quenching process. Further, the inhibitory effects of the complexes on the cell population growth of the human esophageal cancer Eca-109 cells and the cervical cancer HeLa cells were determined by MTT assay, which indicated that both 1 and 2 significantly inhibited the growth of Eca-109 and HeLa cells, the inhibitory activity of complex 1 is stronger than that of 2. We further observed that complex 1 inhibited the growth of HeLa cells through inducing the apoptosis and arresting cell cycle at S phase. Our results suggested that both complexes 1 and 2 have DNA- and protein-binding capacity and antitumor activity.
      Graphical abstract image

      PubDate: 2015-06-08T15:27:47Z
       
  • Synthesis, chemical characterization, computational studies and biological
           activity of new DNA methyltransferases (DNMTs) specific inhibitor.
           Epigenetic regulation as a new and potential approach to cancer therapy
    • Abstract: Publication date: Available online 5 June 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): C. Pellerito , O. Morana , F. Ferrante , G. Calvaruso , A. Notaro , S. Sabella , T. Fiore
      This work deals with the synthesis, the chemical characterization of dibutyltin(IV) complex of caffeic acid (Bu2Sn(IV)HCAF, caf1) and its cytotoxic action on tumor cells. The coordination environment at the tin center was investigated by FTIR, 119Sn{1H} cross polarization magic angle spinning, electrospray ionization mass spectroscopy in the solid state and UV–vis, fluorescence and 1H, 13C and 119Sn NMR spectroscopy in solution phases. Density functional theory study confirmed the proposed structures in solution phase and indicated the most probable stable conformation. The effects on viability of breast cancer MDA-MB231, colorectal cancer HCT116, hepatocellular carcinoma HepG2 and Chang liver cells, an immortalized non-tumor hepatic cell line, have been investigated. The effect of a variation in structure of caf1 found to lead to a change in the respective antiproliferative properties: caf1 induces loss of viability in HCT116, MDA-MB-231, HepG2; the complex shows only moderate effects in non-tumor Chang liver cells. caf1 exerts lower cytotoxic activity than Bu2SnCl2, suggesting that the binding with H3CAF modulates the marked cytotoxic activity exerted by Bu2SnCl2; caf1 displays a considerably more pronounced antitumoural effect towards cell lines than caffeic acid. It is known that caffeic acid can modulate DNA (cytosine-5)-methyltransferases 1 (DNMT1) mediated DNA methylation. In this paper we demonstrate that caf1 treatment was able to induce a time-dependent reduction of global DNA methylated status. This effect was also confirmed by a concomitant reduction DNMT1 expression level. The effect induced by caf1 was more evident not only respect to untreated cells but also compared to H3CAF treated cells.
      Graphical abstract image

      PubDate: 2015-06-08T15:27:47Z
       
  • A versatile salicyl hydrazonic ligand and its metal complexes as antiviral
           agents
    • Abstract: Publication date: Available online 27 May 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): D. Rogolino , M. Carcelli , A. Bacchi , C. Compari , Laura Contardi , E. Fisicaro , A. Gatti , M. Sechi , A. Stevaert , L. Naesens
      Acylhydrazones are very versatile ligands and their coordination properties can be easily tuned, giving rise to metal complexes with different nuclearities. In the last few years, we have been looking for new pharmacophores able to coordinate simultaneously two metal ions, because many enzymes have two metal ions in the active site and their coordination can be a successful strategy to inhibit the activity of the metalloenzyme. As a part of this ongoing research, we synthesised the acylhydrazone H2L and its complexes with Mg(II), Mn(II), Co(II), Ni(II), Cu(II) and Zn(II). Their characterization, both in solution - also by means of potentiometric studies - and in the solid state, evidenced the ability of the o-vanillin hydrazone scaffold to give rise to different types of metal complexes, depending on the metal and the reaction conditions. Furthermore, we evaluated both the free ligand and its metal complexes in in vitro studies against a panel of diverse DNA- and RNA-viruses. In particular, the Mg(II), Mn(II), Ni(II) and Zn(II) complexes had EC50 values in the low micromolar range, with a pronounced activity against vaccinia virus.
      Graphical abstract image

      PubDate: 2015-05-28T07:22:58Z
       
  • Cellular trafficking, accumulation and DNA platination of a series of
           cisplatin-based dicarboxylato Pt(IV) prodrugs
    • Abstract: Publication date: Available online 26 May 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Mauro Ravera , Elisabetta Gabano , Ilaria Zanellato , Ilaria Bonarrigo , Manuela Alessio , Fabio Arnesano , Angela Galliani , Giovanni Natile , Domenico Osella
      A series of Pt(IV) anticancer prodrug candidates, having the equatorial arrangement of cisplatin and bearing two aliphatic carboxylato axial ligands, has been investigated to prove the relationship between lipophilicity, cellular accumulation, DNA platination and antiproliferative activity on the cisplatin-sensitive A2780 ovarian cancer cell line. Unlike cisplatin, no facilitate influx/efflux mechanism appears to operate in the case of the Pt(IV) complexes under investigation, thus indicating that they enter by passive diffusion. While Pt(IV) complexes having lipophilicity comparable to that of cisplatin (negative values of log P o/w) exhibit a cellular accumulation similar to that of cisplatin, the most lipophilic complexes of the series show much higher cellular accumulation (stemming from enhanced passive diffusion), accompanied by greater DNA platination and cell growth inhibition. Even if the Pt(IV) complexes are removed from the culture medium in the recovery process, the level of DNA platination remains very high and persistent in time, indicating efficient storing of the complexes and poor detoxification efficiency.
      Graphical abstract image

      PubDate: 2015-05-28T07:22:58Z
       
  • Reactivity of dinuclear copper(II) complexes towards melanoma cells:
           correlation with its stability, tyrosinase mimicking and nuclease activity
           
    • Abstract: Publication date: Available online 19 May 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Cléia Justino Nunes , Beatriz Essenfelder Borges , Lia Sumie Nakao , Eugénie Peyroux , Renaud Hardré , Bruno Faure , Marius Réglier , Michel Giorgi , Marcela Bach Prieto , Carla Columbano Oliveira , Ana M. Da Costa Ferreira
      In this work, the influence of two new dinuclear copper(II) complexes in the viability of melanoma cells (B16F10 and TM1MNG3) was investigated, with the aim of verifying possible correlations between their cytotoxicity and their structure. One of the complexes had a polydentate dinucleating amine-imine ligand (complex 2), and the other a tridentate imine and a diamine-bridging ligand (complex 4). The analogous mononuclear copper(II) species (complexes 1 and 3, respectively) were also prepared for comparative studies. Crystal structure determination of complex 2 indicated a square-based pyramidal geometry around each copper, coordinated to three N atoms from the ligand and the remaining sites being occupied by either solvent molecules or counter-ions. Complex 4 has a tetragonal geometry. Interactions of these complexes with human albumin protein (HSA) allowed an estimation of their relative stabilities. Complementary studies of their reactivity towards DNA indicated that all of them are able of causing significant oxidative damage, with single and double strand cleavages, in the presence of hydrogen peroxide. However, nuclease activity of the dinuclear species were very similar and much higher than that of the corresponding mononuclear compounds. Although complex 2, with a more flexible structure, exhibits a much higher tyrosinase activity than complex 4, having a more rigid environment around the metal ion, both complexes showed comparable cytotoxicity towards melanoma cells. Corresponding mononuclear complexes showed to be remarkably less reactive as tyrosinase mimics as well as cytotoxic agents. Morever, the dinuclear complexes showed higher cytotoxicity towards more melanogenic cells. The obtained results indicated that the structure of these species is decisive for its activity towards the malignant tumor cells tested.
      Graphical abstract image

      PubDate: 2015-05-23T07:09:57Z
       
  • Reduced accumulation of platinum drugs is not observed in drug-resistant
           ovarian cancer cell lines derived from cisplatin-treated patients
    • Abstract: Publication date: Available online 14 May 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Marina Stukova , Matthew D. Hall , Samantha D. Tsotsoros , James P. Madigan , Nicholas P. Farrell , Michael M. Gottesman
      The resistance of ovarian cancer towards front-line chemotherapy, usually cisplatin or carboplatin in combination with paclitaxel or docetaxel, remains a major clinical challenge. Resistance to these agents has been largely studied using cell lines selected for resistance to agents in vitro. We examined a series of paired cell lines derived from patients with ovarian cancer prior to chemotherapy (PEO1, PEO4, PEO14 and PEA1), and following the acquisition of resistance to a platinum-based chemotherapy regimen (PEO6, PEO23 and PEA2, respectively). All resistant patient lines showed resistance to cisplatin (2-5-fold), but this did not correspond with lowered accumulation. No general cross-resistance was observed for oxaliplatin, paclitaxel or docetaxel, and paclitaxel accumulation was not affected. PEO1 cells carrying BRCA2 mutations were hypersensitive to the PARP inhibitors olaparib and velaparib, but all other cell lines expressing functional forms of BRCA2 were less sensitive. While reduced drug accumulation was not observed, we believe these pairs of lines are of use to researchers studying Pt drug resistance and experimental therapeutics against drug-resistant ovarian cancer.
      Graphical abstract image

      PubDate: 2015-05-18T17:32:13Z
       
  • Oxidovanadium(IV) Sulfate-induced Glucose Uptake in HepG2 Cells through
           IR/Akt Pathway and Hydroxyl Radicals
    • Abstract: Publication date: Available online 15 May 2015
      Source:Journal of Inorganic Biochemistry
      Author(s): Qian Zhao , Deliang Chen , Pingsheng Liu , Taotao Wei , Fang Zhang , Wenjun Ding
      The insulin-mimetic and anti-diabetic properties of vanadium and related compounds have been well documented both in vitro and in vivo. However, the molecular basis of the link between vanadium and the insulin signaling pathway in diabetes mellitus is not fully described. We investigated the effects of reactive oxygen species (ROS) induced by oxidovanadium(IV) sulfate (VOSO4) on glucose uptake and the insulin signaling pathway in human hepatoma cell line HepG2. Exposure of cells to VOSO4 (5-50 μM) resulted in an increase in glucose uptake, insulin receptor (IR) and protein kinase B (Akt) phosphorylation and intracellular ROS generation. Using Western blot, we found that catalase and sodium formate, but not superoxide dismutase, prevented the increase of hydroxyl radical (·OH) generation and significantly decreased VOSO4-induced IR and Akt phosphorylation. These results suggest that VOSO4-induced ·OH radical, which is a signaling species, promotes glucose uptake via the IR/Akt signaling pathway.
      Graphical abstract image

      PubDate: 2015-05-18T17:32:13Z
       
  • Synthesis, crystal structure and investigation of mononuclear copper(II)
           and zinc(II) complexes of a new carboxylate rich tripodal ligand and their
           interaction with carbohydrates in alkaline aqueous solution
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Christopher D. Stewart , Mayra Pedraza , Hadi Arman , Hua-Jun Fan , Eduardo Luiz Schilling , Bruno Szpoganicz , Ghezai T. Musie
      A new carboxylate rich asymmetric tripodal ligand, N-[2-carboxybenzomethyl]-N-[carboxymethyl]-β-alanine (H3camb), and its di-copper(II), (NH4)2[1]2, and di-zinc(II), ((CH3)4 N)2[2]2, complexes have been synthesized as carbohydrate binding models in aqueous solutions. The ligand and complexes have been fully characterized using several techniques, including single crystal X-ray diffraction. The interactions of (NH4)2[1]2 and ((CH3)4 N)2[2]2 with d-glucose, d-mannose, d-xylose and xylitol in aqueous alkaline media were investigated using UV–Vis and 13C-NMR spectroscopic techniques, respectively. The molar conductance, NMR and ESI–MS studies indicate that the complexes dissociate in solution to produce the respective complex anions, 1 − and 2 −. Complexes 1 − and 2 − showed chelating ability towards the naturally abundant and biologically relevant sugars, d-glucose, d-mannose, d-xylose, and xylitol. The complex ions bind to one molar equivalent of the sugars, even in the presence of stoichiometric excess of the substrates, in solution. Experimentally obtained spectroscopic data and computational results suggest that the substrates bind to the metal center in a bidentate fashion. Apparent binding constant values, pK app, between the complexes and the substrates were determined and a specific mode of substrate binding is proposed. The pK app and relativistic density functional theory (DFT) calculated Gibbs free energy values indicate that d-mannose displayed the strongest interaction with the complexes. Syntheses, characterizations, detailed substrate binding studies using spectroscopic techniques, single crystal X-ray diffraction and geometry optimizations of the complex-substrates with DFT calculations are also reported.
      Graphical abstract image

      PubDate: 2015-05-18T17:32:13Z
       
  • Insights into the mechanisms underlying the antitumor activity of an
           oxidovanadium(IV) compound with the antioxidant naringenin. Albumin
           binding studies
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): María S. Islas , Luciana G. Naso , Luis Lezama , María Valcarcel , Clarisa Salado , Meritxell Roura-Ferrer , Evelina G. Ferrer , Patricia A.M. Williams
      Naringenin, a natural antioxidant present in grapefruit, oranges and the skin of tomatoes showed low antioxidant properties among other flavonoids due to its structural characteristics. Since many flavonoids were shown to have cell-killing and antioxidant activities, naringenin was investigated herein. In parallel with its antioxidant activities the flavonoid showed very low cytotoxicity at concentrations up to 100μM against lung (A549) and breast (SKBr3 and MDAMB231) cancer cell lines. Furthermore, a newly-synthesized and characterized complex of naringenin and oxidovanadium(IV) ([VIVO(nar)2]·2H2O, VOnar, with weak ferromagnetic coupling) was also studied. As a result, VOnar acted as a better compound on cell-killing and antioxidant activities (in vitro) than naringenin. The anti-proliferative effect of VOnar was accompanied by reactive oxygen species (ROS) generation, cell membrane and DNA damages, cell cycle arrest, caspase 3/7 activation and mitochondrial potential reduction. The higher parameters observed for the MDAMB231 cell line have been related to its low glutathione (GSH) content. The assays of the interaction of bovine serum albumin (BSA) with the complex showed the affinity of protein toward it and that there is only one binding site on the BSA molecule. However, metal complexation decreased the binding affinity to BSA of naringenin probably due to a steric hindrance of the complex.
      Graphical abstract image

      PubDate: 2015-05-18T17:32:13Z
       
  • Inhibitory effects of nitrite on the reactions of bovine carbonic
           anhydrase II with CO2 and bicarbonate consistent with zinc-bound nitrite
    • Abstract: Publication date: August 2015
      Source:Journal of Inorganic Biochemistry, Volume 149
      Author(s): Per M. Nielsen , Angela Fago
      Carbonic anhydrase (CA) is a zinc enzyme that catalyzes hydration of carbon dioxide (CO2) and dehydration of bicarbonate in red blood cells, thus facilitating CO2 transport and excretion. Bovine CA II may also react with nitrite to generate nitric oxide, although nitrite is a known inhibitor of the CO2 hydration reaction. To address the potential in vivo interference of these reactions and the nature of nitrite binding to the enzyme, we here investigate the inhibitory effect of 10–30mM nitrite on Michaelis–Menten kinetics of CO2 hydration and bicarbonate dehydration by stopped-flow spectroscopy. Our data show that nitrite significantly affects the apparent dissociation constant K M for CO2 (11mM) and bicarbonate (221mM), and the turnover number k cat for the CO2 hydration (1.467×106 s−1) but not for the bicarbonate dehydration (7.927×105 s−1). These effects demonstrate mixed and competitive inhibition for the reaction with CO2 and bicarbonate, respectively, and are consistent with nitrite binding to the active site zinc. The high apparent dissociation constant found here for CO2, bicarbonate and nitrite (16–120mM) are all overall consistent with published data and reveal a large capacity of free enzyme available for binding each of the three substrates at their in vivo levels, with little or no significant interference among reactions. The low affinity of the enzyme for nitrite suggests that the in vivo interaction between red blood cell CA II and nitrite requires compartmentalization at the anion exchanger protein of the red cell membrane to be physiologically relevant.
      Graphical abstract image

      PubDate: 2015-05-18T17:32:13Z
       
 
 
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