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  • Dynamics of dehaloperoxidase-hemoglobin A derived from NMR relaxation spectroscopy and molecular dynamics simulation
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2018-01-12
    Jing Zhao, Mengjun Xue, Dorota Gudanis, Hanna Gracz, Gerhard H. Findenegg, Zofia Gdaniec, Stefan Franzen
    更新日期:2018-01-13
  • 更新日期:2018-01-12
  • Ruthenium dendrimers as carriers for anticancer siRNA
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2018-01-12
    Sylwia Michlewska, Maksim Ionov, Marta Maroto-Díaz, Aleksandra Szwed, Aliaksei Ihnatsyeu-Kachan, Svetlana Loznikova, Dzmitry Shcharbin, Marek Maly, Rafael Gomez Ramirez, Francisco Javier de la Mata, Maria Bryszewska
    更新日期:2018-01-12
  • Reactions of a tetranuclear Pt-thiosemicarbazone complex with model proteins
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2018-01-10
    Tiziano Marzo, Francisco Navas, Damiano Cirri, Antonello Merlino, Giarita Ferraro, Luigi Messori, Adoracion G. Quiroga
    更新日期:2018-01-11
  • Theoretical studies of the second step of the nitric oxide synthase reaction: Electron tunneling prevents uncoupling
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2018-01-10
    Igor Shamovsky, Graham Belfield, Richard Lewis, Frank Narjes, Lena Ripa, Christian Tyrchan, Lisa Öberg, Peter Sjö
    更新日期:2018-01-10
  • Redox-dependent axial ligand replacement and its functional significance in heme-bound iron regulatory proteins
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2018-01-09
    Mariko Ogura, Ryosuke Endo, Haruto Ishikawa, Yukiko Takeda, Takeshi Uchida, Kazuhiro Iwai, Kazuo Kobayash, Koichiro Ishimori
    更新日期:2018-01-10
  • Cytotoxic and anticancer properties of new ruthenium polypyridyl complexes with different lipophilicities
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2018-01-09
    Tikum Florence Anjong, Yu Jeong Jeon, Ju Hyun Lee, Min Hee Park, In Yeong Bae, Sang Heon Kim, Hye Jin Lee, Jinheung Kim
    更新日期:2018-01-09
  • CuI and CuII complexes with phosphine derivatives of fluoroquinolone antibiotics – A comparative study on the cytotoxic mode of action
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2018-01-09
    Aleksandra Bykowska, Urszula K. Komarnicka, Małgorzata Jeżowska-Bojczuk, Agnieszka Kyzioł
    更新日期:2018-01-09
  • Comparative solution equilibrium and structural studies of half-sandwich ruthenium(II)(η6-toluene) complexes of picolinate derivatives
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2018-01-06
    Jelena M. Poljarević, G. Tamás Gál, Nóra V. May, Gabriella Spengler, Orsolya Dömötör, Aleksandar R. Savić, Sanja Grgurić-Šipka, Éva A. Enyedy
    更新日期:2018-01-07
  • Disulfide-masked iron prochelators: Effects on cell death, proliferation, and hemoglobin production
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2018-01-04
    E.A. Akam, R. Utterback, J.R. Marcero, H.A. Dailey, E. Tomat
    更新日期:2018-01-05
  • The role of Ala134 in controlling substrate binding and reactivity in ascorbate peroxidase
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-12-29
    Daniel D. Turner, Latesh Lad, Hanna Kwon, Jaswir Basran, Katherine H. Sharp, Peter C.E. Moody, Emma L. Raven
    更新日期:2017-12-31
  • Imaging of a clickable anticancer iridium catalyst
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-12-29
    Xiuxiu Wang, Mingli Zhu, Fei Gao, Wei Wei, Yong Qian, Hong-Ke Liu, Jing Zhao
    更新日期:2017-12-31
  • Critical analysis of reference studies on the toxicokinetics of aluminum-based adjuvants ☆
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-12-28
    Jean-Daniel Masson, Guillemette Crépeaux, François-Jérôme Authier, Christopher Exley, Romain K. Gherardi
    更新日期:2017-12-31
  • Binding of vanadium to human serum transferrin - voltammetric and spectrometric studies
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-12-26
    Cristina G. Azevedo, Isabel Correia, Margarida M.C. dos Santos, Marino F.A. Santos, Teresa Santos-Silva, James Doutch, Luz Fernandes, Hugo M. Santos, José L. Capelo, João Costa Pessoa
    更新日期:2017-12-27
  • Incorporation of the chemotherapy medication cisplatin into polyamide membrane
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-12-24
    Érica A. de Souza, Lucas A. Rocha, Emerson H. de Faria, Katia J. Ciuffi, Eduardo J. Nassar, Jorge V.L. Silva, Marcelo F. Oliveira, Izaque A. Maia
    更新日期:2017-12-27
  • Cytotoxic activity and structural features of Ru(II)/phosphine/amino acid complexes
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-12-23
    Edjane R. dos Santos, Angelica E. Graminha, Mario S. Schultz, Isabel Correia, Heloisa S. Selistre-de-Araújo, Rodrigo S. Corrêa, Javier Ellena, Elisângela de Paula S. Lacerda, João Costa Pessoa, Alzir A. Batista
    更新日期:2017-12-27
  • 更新日期:2017-12-27
  • Delivery of [Ru(η6-p-cymene)Cl2{Ph2P(CH2)3SPh-κP}] using unfunctionalized and mercapto functionalized SBA-15 mesoporous silica: Preparation, characterization and in vitro study
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-12-22
    David Edeler, Sören Arlt, Vladana Petković, Gerd Ludwig, Dijana Drača, Danijela Maksimović-Ivanić, Sanja Mijatović, Goran N. Kaluđerović
    更新日期:2017-12-22
  • The interaction of pyridoxal isonicotinoyl hydrazone (PIH) and salicylaldehyde isonicotinoyl hydrazone (SIH) with iron
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-12-21
    Yu-Lin Chen, Xiaole Kong, Yuanyuan Xie, Robert C. Hider
    更新日期:2017-12-21
  • Triphenyltin derivatives of sulfanylcarboxylic esters
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-12-20
    José S. Casas, María D. Couce, Agustín Sánchez, Rafael Seoane, José Sordo, Antonio Perez-Estévez, Ezequiel Vázquez-López
    更新日期:2017-12-20
  • Structural characterization of the nitrogenase molybdenum-iron protein with the substrate acetylene trapped near the active site
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-12-13
    Stephen M. Keable, Jacopo Vertemara, Oleg A. Zadvornyy, Brian J. Eilers, Karamatullah Danyal, Andrew J. Rasmussen, Luca De Gioia, Giuseppe Zampella, Lance C. Seefeldt, John W. Peters
    更新日期:2017-12-14
  • Copper redox chemistry of plant frataxins
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-11-27
    Manu Sánchez, Òscar Palacios, Celeste Buchensky, Laura Sabio, Diego Fabian Gomez-Casati, Maria Ayelen Pagani, Mercè Capdevila, Silvia Atrian, Jose M. Dominguez-Vera
    更新日期:2017-12-14
  • Photolabile ruthenium complexes to cage and release a highly cytotoxic anticancer agent
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-11-22
    Jianhua Wei, Anna K. Renfrew

    CHS-828 (N-(6-(4-chlorophenoxy)hexyl)-N′-cyano-N″-4-pyridyl guanidine) is an anticancer agent with low bioavailability and high systemic toxicity. Here we present an approach to improve the therapeutic profile of the drug using photolabile ruthenium complexes to generate light-activated prodrugs of CHS-828. Both prodrug complexes are stable in the dark but release CHS-828 when irradiated with visible light. The complexes are water-soluble and accumulate in tumour cells in very high concentrations, predominantly in the mitochondria. Both prodrug complexes are significantly less cyototoxic than free CHS-828 in the dark but their toxicity increases up to 10-fold in combination with visible light. The cellular responses to light treatment are consistent with release of the cytotoxic CHS-828 ligand.

    更新日期:2017-12-14
  • Is exposure to aluminium adjuvants associated with social impairments in mice? A pilot study
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-11-21
    Sneha K.S. Sheth, Yongling Li, Christopher A. Shaw

    Background Our group has shown that significant correlations exist between rates of Autism Spectrum Disorder (ASD) and total aluminum adjuvants given to children through vaccines in several Western countries. These correlations satisfied eight out of nine Hill criteria for causality. Experimental studies have demonstrated a range of behavioural abnormalities in young mice after postnatal exposure to aluminium. To build on our previous work, the current study will investigate the effect of aluminium adjuvants on social behaviour in mice. Anomalies in social interaction are a key characteristic of those with ASD. Methods Neonatal CD-1 mice pups were injected with either a total of 550 μg of aluminum hydroxide gel (experimental group) or saline (control) spread out during the first two weeks of postnatal life. The mice were then subjected to behavioural tests for social interest and social novelty at postnatal week 8, 17 and 29. p-Values were calculated using the Mann-Whitney and Kruskal Wallis tests. Results Aluminum injected mice showed diminished social interest compared to controls at week 8 (p = 0.016) and 17 (p = 0.012). They also demonstrated abnormal social novelty from controls at week 8 (p = 0.002) and week 29 (p = 0.042). Conclusion This is the first experimental study, to our knowledge, to demonstrate that aluminum adjuvants can impair social behaviour if applied in the early period of postnatal development. The study, however, is insufficient to make any assertive claims about the link between aluminium adjuvants and ASD in humans.

    更新日期:2017-12-14
  • Effective platinum(IV) prodrugs conjugated with lonidamine as a functional group working on the mitochondria
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-11-21
    Hong Chen, Feihong Chen, Weiwei Hu, Shaohua Gou

    Platinum-based anticancer drugs are one of the most widely used anticancer chemotherapeutics in oncology. Lonidamine (LND) could increase the response of human tumor cells to platinum(II) drugs in preclinical studies by working on the mitochondria. Herein, five platinum(IV) prodrugs conjugated with their potentiator LND are prepared, and most of the target complexes achieve improved anticancer activities compared with their platinum(II) precursors. Notably, Pt(NH3)2(LND)Cl3 (complex 1) derived from cisplatin achieve significantly improved anticancer activities against LNCaP cells and could trigger cancer cell death via an apoptotic pathway and the cell cycle arrest mainly at S phases. And the induction of apoptosis by complex 1 in LNCaP cells is closely associated with mitochondrial function disruption and reactive oxygen species (ROS) accumulation. Moreover, it is possessed of the ability to overcome cisplatin-resistance. Further research revealed that complex 1 could be easily reduced to release its platinum(II) precursor and axial ligand by ascorbic acid. All the results provid evidence to support the design strategy of conjugating platinum complexes with its potentiator to improve their anticancer effect.

    更新日期:2017-12-14
  • An optimized low-cost protocol for standardized production of iron-free apoferritin nanocages with high protein recovery and suitable conformation for nanotechnological applications
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-11-21
    Italo Moglia, Margarita Santiago, Álvaro Olivera-Nappa, Mónica Soler

    Ferritin is a globular protein that consists of 24 subunits forming a hollow nanocage structure that naturally stores iron oxyhydroxides. Elimination of iron atoms to obtain the empty protein called apoferritin is the first step to use this organic shell as a nanoreactor for different nanotechnological applications. Different protocols have been reported for apoferritin formation, but some are time consuming, others are difficult to reproduce and protein recovery yields are seldom reported. Here we tested several protocols and performed a complete material characterization of the apoferritin products using size exclusion chromatography, UV–vis spectroscopy, inductively coupled plasma optical emission spectrometry and dynamic light scattering. Our best method removes more than 99% of the iron from loaded holoferritin, recovering 70–80% of the original protein as monomeric apoferritin nanocages. Our work shows that pH conditions of the reduction step and the presence and nature of chelating agents affect the efficiency of iron removal. Furthermore, process conditions also seem to have an influence on the monomer: aggregate proportion present in the product. We also demonstrate that iron contents markedly increase ferritin absorbance at 280 nm. The influence of iron contents on absorbance at 280 nm precludes using this simple spectrophotometric measure for protein determination in ferritin‑iron complexes. Apoferritin produced following our protocol only requires readily-available, cheap and biocompatible reagents, which makes this process standardizable, scalable and applicable to be used for in vivo applications of ferritin derivatives as well as nanotechnological and biotechnological uses.

    更新日期:2017-12-14
  • A series of novel complexes firstly constructed by 1,4-Pheny lenedioxydiacetic acid plays a role in disruption of DNA gene expression and induction of apoptosis
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-11-11
    Mingchang Zhu, Tingting Peng, Na Sun, Xue Qiu, Yang Zhan, Yuqing Ding, Shaozhong Zhang, Enjun Gao

    A set of five metal–organic frameworks, namely, [Cd2(L)2BIP(H2O)2·6H2O]n (1), [Ce(L)1.5(H2O)2·H2O]n (2),[Sm(L)1.5(H2O)2·3H2O]n (3),[Gd(L)1.5(H2O)2·3H2O]n (4),[Ho(L)1.5(H2O)2·3H2O]n (5), have been prepared under hydrothermal conditions (1,4-H2L = 1,4-Pheny lenedioxydiacetic acid; 1,4-BIP = 1,4-bis(2-pyridylmethyl)piperazi-ne; C2H5OH = EtOH). The long BIP ligand (N ⋯ N separation of ca. 8.355 Å) induces interpenetration of 1 to increase both the framework stability and the density of effective catalytic metal centers. Characterization of all complexes has been carried out by means of IR spectroscopy, single crystal and powdered sample X-ray diffraction (PXRD) through conventional and synchrotron radiation, Thermogravimetric (TG), fluorescent measurement (liquid and solid), DNA molecular docking, cancer cell apoptosis morphology through fluorescent inverted microscope, IC50, which the cytotoxic activity of the complexes was tested against two different cancer and one normal cell lines. The results indicate that all the complexes are potential fluorescent light-emitting materials and the flour (2, 3, 4, 5) complexes present remarkable anti-cancer effect.

    更新日期:2017-12-14
  • Aluminum's preferential binding site in proteins: sidechain of amino acids versus backbone interactions
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-11-11
    Jon I. Mujika, Gabriele Dalla Torre, Elena Formoso, Rafael Grande-Aztatzi, Slawomir J. Grabowski, Christopher Exley, Xabier Lopez

    The interaction of aluminum ion Al(III) with polypeptides is a subject of paramount importance, since it is a central feature to understand its deleterious effects in biological systems. Various drastic effects have been attributed to aluminum in its interaction with polypeptides and proteins. These interactions are thought to be established mainly through the binding of aluminum to phosphorylated and non-phosphorylated amino acid sidechains. However, a new structural paradigm has recently been proposed, in which aluminum interacts directly with the backbone of the proteins, provoking drastic changes in their secondary structure and leading ultimately to their denaturation. In the present paper, we use computational methods to discuss the possibility of aluminum to interact with the backbone of peptides and compare it with the known ability of aluminum to interact with amino acid sidechains. To do so, we compare the thermodynamics of formation of prototype aluminum-backbone structures with prototype aluminum-sidechain structures, and compare these results with previous data generated in our group in which aluminum interacts with various types of polypeptides and known aluminum biochelators. Our results clearly points to a preference of aluminum towards amino acid sidechains, rather than towards the peptide backbone. Thus, structures in which aluminum is interacting with the carbonyl group are only slightly exothermic, and they become even less favorable if the interaction implies additionally the peptide nitrogen. However, structures in which aluminum is interacting with negatively-charged sidechains like aspartic acid, or phosphorylated serines are highly favored thermodynamically.

    更新日期:2017-12-14
  • Improving the safety of metal-based drugs by tuning their metabolism with chemoprotective agents
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-11-08
    Jürgen Gailer

    Metal-based drugs remain a tiny minority of all drugs that are on the market. The success story of the quintessential metal-based drug cisplatin (CP), which is intravenously administered to 70% of all cancer patients, however, demonstrates the inherent potential of metal-based drugs. A distinct disadvantage of CP is the dose-limiting severe toxic-side effects that it exerts in patients. To better understand the biomolecular basis for its toxicity, we employed a metallomics method to observe all platinum metabolites that are formed in blood plasma. These investigations revealed that a highly toxic CP-derived hydrolysis product – the highly toxic monoaqua hydrolysis complex (MHC) – is formed within 5 min. More importantly, the application of this research tool has unraveled the mechanisms by which the chemoprotective agents sodium thiosulfate, d-methionine, N-acetyl-cysteine and l-glutathione modulate the metabolism of CP in plasma, namely by rapidly reacting with the MHC to form platinum‑sulfur complexes. Since CP remained in plasma for a considerable time, the possibility of ‘tuning’ its metabolism with chemoprotective agents in a desirable way has emerged. These observations are highly relevant because these chemoprotective agents were previously shown to significantly reduce the toxicity of CP in animal models, often without appreciably affecting its anticancer efficiency. Collectively, these results suggest that the toxicity of other metal-based drugs may be overcome if their metabolism in the bloodstream is adequately tuned with a suitable chemoprotective agent. This principle strategy has considerable potential in terms of harnessing the full potential of bringing more metal-based drugs to the market.

    更新日期:2017-12-14
  • Ilex paraguariensis: Potential antioxidant on aluminium toxicity, in an experimental model of Alzheimer's disease
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-11-07
    Pâmela M. Bortoli, Carla Alves, Eduarda Costa, Ana Paula Vanin, Jéssica R. Sofiatti, Diego P. Siqueira, Rogério M. Dallago, Helen Treichel, Gean Delise L.P. Vargas, Rosilene R. Kaizer

    Ilex paraguariensis, yerba mate is a native plant from the southern region of Brazil. Studies showed that yerba mate has an antioxidant potential, which could help to reduce the risk of developing neurodegenerative diseases, as Alzheimer's Disease (AD). It's known that I. paraguariensis grows in acid soils with aluminium (Al), which is bioavailable in these soils. Al has a neurotoxic potential related with the progression of neurological disorders. This study aim was to evaluate the potential of I. paraguariensis in the etiology of AD using strains of Caenorhabditis elegans and the concentration of Al and antioxidants in the yerba mate extract. The results of the I. paraguariensis infusions made at 65 °C and at 75° C show that there was no significant difference between both temperatures when preparing the tea infusion in relation to the presence of Al, methylxanthines, phenolic compounds and flavonoids. Additionally, in the case of Al, there was no difference between the extracts prepared at both temperatures. The behavioral parameters of C. elegans were altered after a long-term exposure to both factors: I. paraguariensis extract and Al. Through the antioxidant levels results along with the Al content on the Acetylcholinesterase (AChE) activity it is possible to observe that the acute and chronic exposure to Al and I. paraguariensis leaves extract are very similar to wild-type worms. Moreover, we can observe that the results in both the transgenic strains long-term exposed to I. paraguariensis leaves extract and to the Al concentrations presented an increase in the AChE activity.

    更新日期:2017-12-14
  • Cognitive dysfunction associated with aluminum hydroxide-induced macrophagic myofasciitis: A reappraisal of neuropsychological profile
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-10-06
    Mehdi Aoun Sebaiti, Paul Kauv, Anaïs Charles-Nelson, Axel Van Der Gucht, Paul Blanc-Durand, Emmanuel Itti, Romain K. Gherardi, Anne-Catherine Bachoud-Levi, François Jérôme Authier

    Patients with macrophagic myofasciitis (MMF) present with diffuse arthromyalgias, chronic fatigue, and cognitive disorder. Representative features of MMF-associated cognitive dysfunction include attentional dysfunction, dysexecutive syndrome, visual memory deficit and left ear extinction. Our study aims to reevaluate the neuropsychological profile of MMF. 105 unselected consecutive MMF patients were subjected to a neuropsychological battery of screen short term and long-term memory, executive functions, attentional abilities, instrumental functions and dichotic listening. From these results, patients were classified in four different groups: Subsymptomatic patients (n = 41) with performance above pathological threshold (− 1.65 SD) in all tests; Fronto-subcortical patients (n = 31) who showed pathological results at executive functions and selective attention tests; Papezian patients (n = 24) who showed pathological results in storage, recognition and consolidation functions for episodic verbal memory, in addition to fronto-subcortical dysfunction; and Extinction patients (n = 9) who had a left ear extinction at dichotic listening test in association to fronto-subcortical and papezian dysfunction. In addition, inter-test analysis showed that patients with apparently normal cognitive functions (Subsymptomatic group) performed significantly worse to attention tests compared to others. In conclusion, our study shows that (i) most patients have specific cognitive deficits; (ii) all patients with cognitive deficit have impairment of executive functions and selective attention; (iii) patients without measurable cognitive deficits display significant weakness in attention; (iv) episodic memory impairment affects verbal, but not visual, memory; (v) none of the patients show an instrumental dysfunction.

    更新日期:2017-12-14
  • Reprint of: Impact of the corrin framework of vitamin B12 on the electrochemical carbon-skeleton rearrangement in comparison to an imine/oxime planar ligand; tuning selectivity in 1,2-migration of a functional group by controlling electrolysis potential
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-09-29
    Keishiro Tahara, Ling Pan, Ryoko Yamaguchi, Hisashi Shimakoshi, Masaaki Abe, Yoshio Hisaeda

    Among the coenzyme B12-dependent enzymes, methylmalonyl-CoA mutase (MMCM) catalyzes the carbon-skeleton rearrangement reaction between R-methylmalonyl-CoA and succinyl-CoA. Diethyl 2-bromomethyl-2-phenylmalonate, an alkyl bromide substrate having two different migrating groups (phenyl and carboxylic ester groups) on the β-carbon, was applied to the electrolysis mediated by a hydrophobic vitamin B12 model complex, heptamethyl cobyrinate perchlorate in this study. The electrolysis of the substrate at − 1.0 V vs. Ag-AgCl by light irradiation afforded the simple reduced product (diethyl 2-methyl-2-phenylmalonate) and the phenyl migrated product (diethyl 2-benzyl-2-phenylmalonate), as well as the electrolysis of the substrate at − 1.5 V vs. Ag-AgCl in the dark. The electrolysis of the substrate at − 2.0 V vs. Ag-AgCl afforded the carboxylic ester migrated product (diethyl phenylsuccinate) as the major product. The selectivity for the migrating group was successfully tuned by controlling the electrolysis potential. We clarified that the cathodic chemistry of the Co(III) alkylated heptamethyl cobyrinate is critical for the selectivity of the migrating group through mechanistic investigations and comparisons to the simple vitamin B12 model complex, an imine/oxime-type cobalt complex.

    更新日期:2017-12-14
  • Phytoplankton responses to aluminum enrichment in the South China Sea
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-09-22
    Linbin Zhou, Jiaxing Liu, Shuai Xing, Yehui Tan, Liangmin Huang

    Compared to extensive studies reporting the aluminum (Al) toxicity to terrestrial plants and freshwater organisms, very little is known about how marine phytoplankton responds to Al in the field. Here we report the marine phytoplankton responses to Al enrichment in the South China Sea (SCS) using on-deck bottle incubation experiments during eight cruises from May 2010 to November 2013. Generally, Al addition alone enhanced the growth of diatom and Trichodesmium, and nitrogen fixation, but it inhibited the growth of dinoflagellates and Synechococcus. Nevertheless, Al addition alone did not influence the chlorophyll a concentration of the entire phytoplankton assemblages. By adding nitrate and phosphate simultaneously, Al enrichment led to substantial increases in chlorophyll a concentration (especially that of the picophytoplankton < 3 μm), and cell abundances of diatom and photosynthetic picoeukaryotes. These results indicate varied responses of phytoplankton in different size fractions and taxonomic groups to Al enrichment. Further, by simultaneously adding different macronutrients and/or sufficient trace metals including iron, we found that the phytoplankton responses to Al enrichment were relevant to nutrients coexisting in the environment. Al enrichment may give some phytoplankton a competitive edge over using nutrients, especially the limited ones. The possible influences of Al on the competitors and grazers (predators) of some phytoplankton might indirectly contribute to the positive responses of the phytoplankton to Al enrichment. Our results indicate that Al may influence marine carbon cycle by impacting phytoplankton growth and structure in natural seawater.

    更新日期:2017-12-14
  • Behaviour of aluminium in forest soils with different lithology and herb vegetation cover
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-09-20
    Petra Hubová, Václav Tejnecký, Michaela Češková, Luboš Borůvka, Karel Němeček, Ondřej Drábek

    The aim of this study was to determine the content, distribution and behaviour of Al in soils under beech forest with different parent rock, and to assess the role of herbaceous vegetation on soil Al behaviour. We hypothesize that the contents of elements in the soil sorption complex (Al etc.) are strongly influenced by vegetation cover. Also, low molecular mass organic acids (LMMOA) can be considered as an indicator of soil organic matter (SOM) decomposition and vegetation litter turnover. Speciation of LMMOA, nutrition content (PO43 −, Ca2 +, K +) and element composition in aqueous extracts were determined by means of ion chromatography and inductively coupled plasma - optical emission spectrometry (ICP-OES) respectively. Active and exchangeable pH, sorption characteristics and exchangeable Al (Alex) were determined in BaCl2 extracts by ICP-OES. Elemental composition of parent rocks was assessed by means of X-ray fluorescence spectroscopy. Herb-poor localities showed lower pH, less nutrients (PO43 −, Ca2 +, K +), less LMMOA, a larger stock of SOM and greater cation exchange capacity. There was also lower mobilisation of Al in organic horizons, which explains the larger pools of Al. Generally, we can conclude that LMMOA, and thus soil vegetation cover, play an important role in the Al soil cycle.

    更新日期:2017-12-14
  • Ni-elimination from the active site of the standard [NiFe]‑hydrogenase upon oxidation by O2
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-09-14
    Koji Nishikawa, Satoko Mochida, Takeshi Hiromoto, Naoki Shibata, Yoshiki Higuchi

    Hydrogenase is a key enzyme for a coming hydrogen energy society, because it has strong catalytic activities on both uptake and production of dihydrogen. We, however, have to overcome the sensitivity against O2 of the enzyme, because hydrogenase is, generally, easily inactivated in the presence of O2. In this study, we have revisited the crystal structures of [NiFe]‑hydrogenase from sulfate-reducing bacterium in the several oxidized and reduced conditions. Our results revealed that the Ni‐Fe active site of the enzyme exposed into O2 showed two forms, Form-1 and Form-2. The Ni‐Fe active site in Form-1 showed the typical Ni‐B (inactive ready) structure, whereas those in Form-2 lost Ni with no relation to an exposure time to O2, and two cysteinyl sulfur ligands made a disulfide bond. On the other hand, the formation of sulfenylation of the cysteinyl ligand to Ni, which is often observed in the oxidized form, did not correlate with the Ni-elimination, but with exposure time to O2.

    更新日期:2017-12-14
  • Evaluation of aluminium mobilization from its soil mineral pools by simultaneous effect of Aspergillus strains' acidic and chelating exometabolites
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-09-13
    Filip Polák, Martin Urík, Marek Bujdoš, Peter Uhlík, Peter Matúš

    This contribution investigates aluminium mobilization from main aluminium pools in soils, phyllosilicates and oxyhydroxides, by acidic and chelating exometabolites of common soil fungi Aspergillus niger and A. clavatus. Their exometabolites' acidity as well as their ability to extract aluminium from solid mineral phases differed significantly during incubation. While both strains are able to mobilize aluminium from boehmite and aluminium oxide mixture to some extent, A. clavatus struggles to mobilize any aluminium from gibbsite. Furthermore, passive and active fungal uptake of aluminium enhances its mobilization from boehmite, especially in later growth phase, with strong linear correlation between aluminium bioaccumulated fraction and increasing culture medium pH. We also provide data on concentrations of oxalate, citrate and gluconate which are synthesized by A. niger and contribute to aluminium mobilization. Compared to boehmite-free treatment, fungus reduces oxalate production significantly in boehmite presence to restrict aluminium extraction efficiency. However, in presence of high phyllosilicates' dosages, aluminium is released to an extent that acetate and citrate is overproduced by fungus. Our results also highlight fungal capability to significantly enhance iron and silicon mobility as these elements are extracted from mineral lattice of phyllosilicates by fungal exometabolites alongside aluminium.

    更新日期:2017-12-14
  • Aluminium-induced cell death requires upregulation of NtVPE1 gene coding vacuolar processing enzyme in tobacco (Nicotiana tabacum L.)
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-09-12
    Koki Kariya, Yoshiyuki Tsuchiya, Takayuki Sasaki, Yoko Yamamoto

    Cell death mechanism triggered by aluminium (Al) ion was investigated at root apex of tobacco (cultivar Bright Yellow) and in cultured tobacco cell line BY-2 derived from Bright Yellow, focusing on VPE genes (NtVPE1a, NtVPE1b, NtVPE2, NtVPE3). Cell death was detected as a loss of integrity of the plasma membrane by vital staining with fluorescein diacetate (in root apex) and Evans blue (in BY-2), respectively. At root apex, the upregulation of gene expression of VPE1a and VPE1b was observed significantly after 9 h of Al exposure in parallel with an enhancement of cell death, while the upregulation of VPE2 and VPE3 were observed later. Similarly, in BY-2 cells, the upregulation of VPE1a and VPE1b and the enhancement of cell death were synchronously observed after 3-h exposure to Al, while the upregulation of VPE2 and VPE3 occurred later. RNA interference (RNAi) lines of each of the VPEs were constructed in BY-2 cells. Comparative studies between wild-type and the RNAi lines indicated that both Al-enhanced VPE activity and Al-induced cell death were significantly suppressed in the RNAi lines of VPE1 (dual suppressor of VPE1a and VPE1b), but not in the RNAi lines of VPE2 and that of VPE3. Taken together, we conclude that the upregulation of VPE1 gene expression and following enhancement of VPE activity under Al stress cause cell death in actively growing or elongating cells of tobacco.

    更新日期:2017-12-14
  • Phosphorogenic sensors for biothiols derived from cyclometalated iridium(III) polypyridine complexes containing a dinitrophenyl ether moiety
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-09-12
    Karson Ka-Shun Tso, Hua-Wei Liu, Kenneth Kam-Wing Lo

    We report the synthesis and characterization of three cyclometalated iridium(III) polypyridine complexes containing a 2,4-dinitrophenyl ether moiety [Ir(pq)2(N^N)](PF6) (Hpq = 2-phenylquinoline; N^N = 4-(N-(4-(2,4-dinitrophenoxy)benzyloxy)carbonyl)aminomethyl-4′-methyl-2,2′-bipyridine (bpy-dinitro-1) (1a), 4-(2,4-dinitrophenoxy)methyl-4′-methyl-2,2′-bipyridine (bpy-dinitro-2) (2a), 4-(4-(2,4-dinitrophenoxy)phenyl)-2,2′-bipyridine (bpy-dinitro-3) (3a)) as intracellular sensors for biothiols. Due to the quenching effect of the dinitroaromatic moiety, these complexes were extremely weakly emissive. Upon the reaction with biothiols, however, the emission was turned on as a consequence of the departure of the quenching unit. The results from a range of experiments demonstrated that complex 1a was noncytotoxic under the conditions used for confocal imaging, showed facile cellular uptake, and can serve as a phosphorogenic intracellular sensor for biothiols including glutathione (GSH) and hydrogen sulfide.

    更新日期:2017-12-14
  • The catalytic cycle of nitrous oxide reductase — The enzyme that catalyzes the last step of denitrification
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-09-11
    Cíntia Carreira, Sofia R. Pauleta, Isabel Moura

    The reduction of the potent greenhouse gas nitrous oxide requires a catalyst to overcome the large activation energy barrier of this reaction. Its biological decomposition to the inert dinitrogen can be accomplished by denitrifiers through nitrous oxide reductase, the enzyme that catalyzes the last step of the denitrification, a pathway of the biogeochemical nitrogen cycle. Nitrous oxide reductase is a multicopper enzyme containing a mixed valence CuA center that can accept electrons from small electron shuttle proteins, triggering electron flow to the catalytic sulfide-bridged tetranuclear copper “CuZ center”. This enzyme has been isolated with its catalytic center in two forms, CuZ*(4Cu1S) and CuZ(4Cu2S), proven to be spectroscopic and structurally different. In the last decades, it has been a challenge to characterize the properties of this complex enzyme, due to the different oxidation states observed for each of its centers and the heterogeneity of its preparations. The substrate binding site in those two “CuZ center” forms and which is the active form of the enzyme is still a matter of debate. However, in the last years the application of different spectroscopies, together with theoretical calculations have been useful in answering these questions and in identifying intermediate species of the catalytic cycle. An overview of the spectroscopic, kinetics and structural properties of the two forms of the catalytic “CuZ center” is given here, together with the current knowledge on nitrous oxide reduction mechanism by nitrous oxide reductase and its intermediate species.

    更新日期:2017-12-14
  • A proteomic approach to the mechanisms underlying activation of aluminium resistance in roots of Urochloa decumbens
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-09-10
    Catalina Arroyave, Roser Tolrà, Livia Chaves, Marcelo Claro de Souza, Juan Barceló, Charlotte Poschenrieder

    The mechanisms of extreme Al-resistance in Urochloa decumbens are not established. Full resistance expression requires a lag time of 72–96 h and is preceded by a sensitive phase (24–48 h) with Al-induced root growth inhibition. The aim here was to identify key processes of the activation phase of Al-resistance analysing both root exudates and comparative root proteome. Samples were taken after 0, 24 and 96 h exposure to 0 or 200 μM Al. Al-induced stimulation of citrate and oxalate efflux was limited to the sensitive phase. Only 11 proteins revealed Al-induced abundance differences; six were identified. After 24 h, phenylalanine ammonium lyase (PAL), methionine synthase (MS), and deoxymugineic acid synthase (DMAS) decreased, while acid phosphatase (APase) abundance increased. Coincident with growth recovering, PAL and MS, but not DMAS, returned to initial levels. After 96 h, γ‑carbonic anhydrase (γ‑CA) and adenylate kinase (AK) along with two unidentified proteins were more abundant. In conclusion, few protein changes characterize the initial response to Al in signalgrass. During the alarm phase, changes are related to P-mobilization, downregulation of Fe-acquisition, reduction of phenolic biosynthesis, and small stimulation of organic acid exudation. After recovering (resistant phase), biosynthesis of phenolics and methionine, but not Fe-mobilization are re-established. Full expression of Al-resistance is characterized by enhanced γ‑CA mediating mitochondrial complex I assembly and increased AK abundance indicating higher root respiration and better provision of ADP and Mg2 + to ATP synthase, respectively. The unidentified proteins and the specific role of γ‑CA in Al resistance of U. decumbens will centre future research.

    更新日期:2017-12-14
  • Insights into the recognition and electron transfer steps in nitric oxide reductase from Marinobacter hydrocarbonoclasticus
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-09-07
    Susana Ramos, Rui M. Almeida, Cristina M. Cordas, José J.G. Moura, Sofia R. Pauleta, Isabel Moura

    Marinobacter hydrocarbonoclasticus nitric oxide reductase, cNOR, is an integral membrane protein composed of two subunits with different roles, NorC (electron transfer) and NorB (catalytic) that receives electrons from the soluble cytochrome c552 and reduces nitric oxide to nitrous oxide in the denitrification pathway. The solvent-exposed domain of NorC, harboring a c-type heme was heterologously produced, along with its physiological electron donor, cytochrome c552. These two proteins were spectroscopically characterized and shown to be similar to the native proteins, both being low-spin and Met-His coordinated, with the soluble domain of NorC presenting some additional features of a high-spin heme, which is consistent with the higher solvent accessibility of its heme and weaker coordination of the methionine axial ligand. The electron transfer complex between the two proteins has a 1:1 stoichiometry, and an upper limit for the dissociation constant was estimated by 1H NMR titration to be 1.2 ± 0.4 μM. Electrochemical techniques were used to characterize the interaction between the proteins, and a model structure of the complex was obtained by molecular docking. The electrochemical observations point to the modulation of the NorC reduction potential by the presence of NorB, tuning its ability to receive electrons from cytochrome c552.

    更新日期:2017-12-14
  • Anticancer Ru(η6-p-cymene) complexes of 2-pyridinecarbothioamides: A structure–activity relationship study
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-09-04
    Jahanzaib Arshad, Muhammad Hanif, Sanam Movassaghi, Mario Kubanik, Amir Waseem, Tilo Söhnel, Stephen M.F. Jamieson, Christian G. Hartinger

    Ru(II) and Os(II) complexes of 2-pyridinecarbothioamide ligands were introduced as orally administrable anticancer agents (S.M. Meier, M. Hanif, Z. Adhireksan, V. Pichler, M. Novak, E. Jirkovsky, M.A. Jakupec, V.B. Arion, C.A. Davey, B.K. Keppler, C.G. Hartinger, Chem. Sci., 2013, 4, 1837–1846). In order to identify structure-activity relationships, a series of N-phenyl substituted pyridine-2-carbothiamides (PCAs) were obtained by systematically varying the substituents at the phenyl ring. The PCAs were then converted to their corresponding RuII(η6-p-cymene) complexes and characterized spectroscopically and by X-ray diffraction as well as in terms of stability in water and HCl. The cytotoxic activity of the PCA ligands and their respective organoruthenium compounds was evaluated in a panel of cell lines (HCT116, H460, SiHa and SW480). The lipophilic PCAs 1–4 showed cytotoxicity in the low micromolar range and 6 was the most potent compound of the series with an IC50 value of 1.1 μM against HCT116 colon cancer cells. These observations were correlated with calculated octanol/water partition coefficient (clogP) data and quantitative estimated druglikeness. A similar trend as for the PCAs was found in their Ru complexes, where the complexes with more lipophilic ligands proved to be more cytotoxic in all tested cell lines. In general, the PCAs and their organoruthenium derivatives demonstrated excellent drug-likeness and cytotoxicity with IC50 values in the low micromolar range, making them interesting candidates for further development as orally active anticancer agents.

    更新日期:2017-12-14
  • NMR studies of the non-haem Fe(II) and 2-oxoglutarate-dependent oxygenases
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-09-04
    Naasson M. Mbenza, Praveen G. Vadakkedath, Duncan J. McGillivray, Ivanhoe K.H. Leung

    The non-haem Fe(II) and 2-oxoglutarate (2OG)-dependent oxygenases belong to a superfamily of structurally-related enzymes that play important biological roles in plants, microorganisms and animals. Structural, mechanistic and functional studies of 2OG oxygenases require efficient and effective biophysical tools. Nuclear magnetic resonance (NMR) spectroscopy is a useful tool to study this enzyme superfamily. It has been applied to obtain information about enzyme kinetics, identify and characterise 2OG oxygenase-catalysed oxidation products, elucidate the catalytic mechanism, monitor ligand binding and study protein dynamics. This review summarises the types of information that NMR spectroscopy can provide in the studies of 2OG oxygenases, highlights the advantages of the technique and describes its drawbacks.

    更新日期:2017-12-14
  • Geometric effects on OO bond scission of copper(II)-alkylperoxide complexes
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-09-01
    Tsukasa Abe, Yuma Morimoto, Kaoru Mieda, Hideki Sugimoto, Nobutaka Fujieda, Takashi Ogura, Shinobu Itoh

    Copper(II) complexes supported by N3-tridentate ligands, consisting of a rigid cyclic diamine (8-membered cyclic-diamine; L8 or 7-membered cyclic-diamine; L7) and a 2-(2-pyridyl)ethyl (-CH2CH2Py) group, were synthesized and structurally characterized. Reaction of the copper(II) complexes and cumene hydroperoxide (CmOOH) in the presence of triethylamine in CH3CN gave the corresponding cumylperoxide complexes L8CuIIOOCm and L7CuIIOOCm. The UV–vis and EPR spectra suggested that L8CuIIOOCm takes a tetrahedrally distorted structure, whereas L7CuIIOOCm has a planar geometry in solution. Resonance Raman spectra of these alkylperoxide complexes indicated that the O-O stretching vibration energy of L8CuIIOOCm (νO–O = 878 cm− 1) is somewhat lower than that of L7CuIIOOCm (νO–O = 881 cm− 1). Such a difference in O-O bond strength is reflected to the reactivity difference of these two alkylperoxide complexes. Namely, the reactivity L8CuIIOOCm toward CHD (1,4-cyclohexadiene) as well as solvent molecule (CH3CN) is higher than that of L7CuIIOOCm due to the weaker O-O bond of the former complex as compared to that of the latter complex. Geometric effects on the reactivity induced by the supporting ligands are discussed.

    更新日期:2017-12-14
  • Aluminum exposure for 60 days at an equivalent human dietary level promotes peripheral dysfunction in rats
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-08-25
    Caroline Silveira Martinez, Gema Vera, José Antonio Uranga Ocio, Franck Maciel Peçanha, Dalton Valentim Vassallo, Marta Miguel, Giulia Alessandra Wiggers

    Aluminum (Al) is a neurotoxic associated with a number of chronic human diseases. We investigated the effects of Al exposure at doses similar to human dietary levels and at a high level exposure to Al on the peripheral nervous system. Wistar male rats were divided into two major groups and received orally: 1) First group – Low level - rats were subdivided and treated for 60 days: a) Control – received ultrapure water; b) AlCl3 – received Al at 8.3 mg/kg body weight (bw) for 60 days; and 2) Second group – High level - rats were subdivided and treated for 42 days: C) Control – received ultrapure water through oral gavage; d) AlCl3 – received Al at 100 mg/kg bw for 42 days. Von Frey hair test, plantar test, the presence of catalepsy and the spontaneous motor activity were investigated. Reactive oxygen species, lipid peroxidation and total antioxidant capacity, immunohistochemistry to investigate the nerve inflammation and, the specific presence of Al in the sciatic nerve fibers were investigated. Al exposure at a representative human dietary level promotes the development of mechanical allodynia, catalepsy, increased inflammation in the sciatic nerve, systemic oxidative stress and, is able to be retained in the sciatic nerve. The effects of low-dose Al were similar to those found in rats exposed to Al at a dose much higher (100 mg/kg). Our findings suggest that Al may be considered toxic for the peripheral nervous system, thus inducing peripheral dysfunction.

    更新日期:2017-12-14
  • Kinetic analysis of and platinum(II) migration in the reactions of tetrazolato-bridged dinuclear platinum(II) complexes with nucleotides
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-08-25
    Masako Uemura, Seiji Komeda

    The series of tetrazolato-bridged complexes with the formula [{cis‑Pt(NH3)2}2(μ-OH)(μ-5-H-tetrazolato-N1,N2)]2 + (5-H-X) or [{cis‑Pt(NH3)2}2(μ-OH)(μ-5-R-tetrazolato-N2,N3)]n + (R = H (5-H-Y), CH3 (1), CH2COOCH2CH3 (2), CH2COO– (3), n = 2 (5-H-Y, 1, 2) or 1 (3)) are promising candidate complexes for formulation as next-generation platinum-based anticancer drugs that form multimodal bindings with DNA molecules. These multimodal bindings involve both non-covalent and covalent interactions, the latter of which are acknowledged to be essential for platinum-based drugs to exert their anticancer activity. In the present study, the tetrazolato-bridged complexes reacted with two molar equivalents of guanosine-5′-monophosphate (GMP) to yield the 1:2 reaction products [{cis‑Pt(NH3)2(GMP-N7)}2(μ-5-R-tetrazolato-N1,N3)]2 − or 1 −. This reaction was accompanied by an intramolecular Pt(II) migration that contributed to the formation of diverse DNA crosslinking, such as interhelical crosslinks. The second-order reaction rate constants for the reactions performed in phosphate-buffered D2O solution showed that the reactivity of the complexes decreased in the order 5-H-X ≳ 5-H-Y > 2 ≳ 1 > 3 and that reactivity was correlated with the cytotoxicity of the complexes. A similar result was obtained for the reaction of the complexes with calf thymus DNA in which the formation of covalent DNA adducts was quantified by means of inductively coupled plasma mass spectrometry. These results suggest that overall charge affects the kinetics of the reactions of platinum complexes with GMP and calf thymus DNA. Thus, the positive charge of the complexes affects not only the non-covalent but also the covalent interactions between the complexes and nucleotides and DNA, which are negatively charged molecules.

    更新日期:2017-12-14
  • The crystal structures of a copper-bound metallochaperone from Saccharomyces cerevisiae
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-08-24
    Mihwa Lee, N. Dinesha G. Cooray, Megan J. Maher

    Atx1 is a metallochaperone protein from the yeast Saccharomyces cerevisiae (yAtx1) that plays a major role in copper homeostasis in this organism. yAtx1 functions as a copper transfer protein by shuttling copper to the secretory pathway to control intracellular copper levels. Here we describe the first crystal structures of yAtx1 that have been determined in the presence of Cu(I). The structures from two different crystal forms have been solved and refined to resolutions of 1.65 and 1.93 Å. In contrast to the previous metallated crystal structure of yAtx1 where a single Hg(II) atom was coordinated by one yAtx1 molecule, the Cu(I)-yAtx1 was crystallised as a dimer in both crystal forms, sharing one Cu(I) atom between two yAtx1 molecules. This is consistent with the crystal structure of the human homologue Cu(I)-hAtox1. Overall the structures in the two different crystal forms of Cu(I)-yAtx1 are remarkably similar to that of Cu(I)-hAtox1. However, subtle structural differences between Cu(I)-yCtr1 and Cu(I)-hAtox1 are observed in copper coordination geometries and in the conformations of Loop 2, with the latter potentially contributing to differential interactions and copper transfer mechanisms with membrane transport copper uptake systems.

    更新日期:2017-12-14
  • An XAS investigation of the nickel site structure in the transcriptional regulator InrS
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-08-10
    Carolyn E. Carr, Andrew W. Foster, Michael J. Maroney

    InrS (Internal nickel-responsive Sensor) is a transcriptional repressor of the nickel exporter NrsD and de-represses expression of the exporter upon binding Ni(II) ions. Although a crystal structure of apo-InrS has been reported, no structure of the protein with metal ions bound is available. Herein we report the results of metal site structural investigations of Ni(II) and Cu(II) complexes of InrS using X-ray absorption spectroscopy (XAS) that are complementary to data available from the apo-InrS crystal structure, and are consistent with a planar four-coordinate [Ni(His)2(Cys)2] structure, where the ligands are derived from the side chains of His21, Cys53, His78, and Cys82. Coordination of Cu(II) to InrS forms a nearly identical planar four-coordinate complex that is consistent with a simple replacement of the Ni(II) center by Cu(II).

    更新日期:2017-12-14
  • Reprint of “Anticancer activity of hydroxy- and sulfonamide-azobenzene platinum(II) complexes in cisplatin-resistant ovarian cancer cells”
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-08-08
    Katia G. Samper, Sierra C. Marker, Pau Bayón, Samantha N. MacMillan, Ivan Keresztes, Òscar Palacios, Justin J. Wilson

    The syntheses of three platinum(II) complexes bearing sulfonamide-((E)-2-(4-methylphenylsulfonamido)-2′,6′-difluoroazobenzene, HL1) and hydroxy-azo-2,6-difluorobenzene ((E)-2-((2,6-difluorophenyl)diazenyl)phenol, HL2) bidentate ligands is described. These complexes, [Pt(L1)(DMSO)Cl] (1), [Pt(L2)(DMSO)Cl] (2), and [Pt(L2)2] (3), were characterized by multinuclear NMR spectroscopy, mass spectrometry, and X-ray crystallography. Despite bearing azobenzene functional groups, none of the three complexes undergo photoisomerization. The anticancer activities of these complexes were evaluated in wild-type (A2780) and cisplatin-resistant (A2780CP70) ovarian cancer cells. All three complexes exhibited IC50 values below 10 μM and displayed similar activity in both A2780 and A2780CP70 cell lines, indicating that they are not cross-resistant with cisplatin. The DNA-binding properties of 1–3 were investigated by circular dichroism spectroscopy and by agarose gel electrophoresis. Both studies suggest that 1 and 2 form monofunctional DNA adducts.

    更新日期:2017-12-14
  • Dimeric and trimeric homo- and heteroleptic hydroxamic acid macrocycles formed using mixed-ligand Fe(III)-based metal-templated synthesis
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-08-01
    Athavan Sresutharsan, William Tieu, Tomas Richardson-Sanchez, Cho Zin Soe, Rachel Codd

    Macrocyclic hydroxamic acids coordinate Fe(III) with high affinity as part of siderophore-mediated bacterial iron acquisition. Trimeric hydroxamic acid macrocycles, such as desferrioxamine E (DFOE), are prevalent in nature, with fewer dimeric macrocycles identified, including putrebactin (pbH2), avaroferrin (avH2), bisucaberin (bsH2) and alcaligin (alH2). This work used metal-templated synthesis (MTS) to pre-assemble complexes between one equivalent of Fe(III) and two equivalents of 4-((4-aminobutyl)(hydroxy)amino)-4-oxobutanoic acid (BBH) or 4-((5-aminopentyl)(hydroxy)amino)-4-oxobutanoic acid (PBH). Following peptide coupling, the respective Fe(III) complexes of pbH2 or bsH2 were formed, which analysed by LC-MS under acidic pH as [Fe(pb)]+ ([M]+, m/zobs 426.1) or [Fe(bs)]+ ([M]+, m/zobs 454.2). The mixed-ligand 1:1:1 Fe(III):BBH:PBH system furnished [Fe(pb)]+ and [Fe(bs)]+, together with chimeric [Fe(av)]+ ([M]+, m/zobs 440.2). The deviation from the expected 1:2:1 distribution of [Fe(pb)]+:[Fe(av)]+:[Fe(bs)]+ to 1:3.2:1.6 suggested the MTS-mediated formation of dimeric macrocycles could be influenced by steric effects in the pre-complex and/or cavity size, as governed by the monomer. 21-Membered avH2 defined the lower boundary of the optimal architecture. Mixed-ligand MTS between Fe(III):PBH-d4:ret-PBH at 1:1.5:1.5, where ret-PBH = 3-(6-amino-N-hydroxyhexanamido)propanoic acid, gave four Fe(III)-loaded trimeric hydroxamic acid macrocycles in a distribution of 1.0:3.0:2.9:1.1 that closely matched the expected distribution 1:3:3:1 for a system without any kinetic and/or thermodynamic bias. Apo-macrocycles pbH2, avH2 and bsH2 were produced upon incubation with diethylenetriaminepentaacetic acid (DTPA) and co-eluted with a biosynthetic mixture of the native macrocycles. The work has demonstrated the utility of single- and mixed-ligand MTS for producing a variety of homo- and heteroleptic dimeric hydroxamic acid macrocycles as Fe(III) complexes and free ligands.

    更新日期:2017-12-14
  • The influence of the ethane-1,2-diamine ligand on the activity of a monofunctional platinum complex
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-07-29
    Marcus E. Graziotto, Mia C. Akerfeldt, Adam P. Gunn, Kylie Yang, Mark V. Somerville, Nicholas V. Coleman, Blaine R. Roberts, Trevor W. Hambley, Elizabeth J. New

    The continued use of platinum-based chemotherapeutic drugs in the clinic mandates the need for further investigation of the biological activity of structural analogues of the clinically approved complexes. Of interest are monofunctional platinum(II) complexes, which bear only one labile ligand, for which it is believed that each complex binds to DNA only once. Pyriplatin ([PtCl(NH3)2(py)]+) and enpyriplatin ([PtCl(en)(py)]+) are both monofunctional platinum(II) complexes that bear a pyridine ligand and a labile chlorido ligand, differing in their cis‑ammine and ethane-1,2-diamine (en) ligands respectively. Despite their similar structure, the complexes exhibit dramatically different cytotoxicities. In this study, we synthesized and characterized both complexes in terms of their cytotoxicity, lipophilicity, DNA binding and cellular accumulation. There was no significant difference between the lipophilicities of the complexes and both complexes exhibited monofunctional type binding, but it was the temporal accumulation profiles of the two complexes which differed greatly. The complexes were further analyzed with size exclusion chromatography coupled with inductively coupled plasma mass spectrometry (SEC-ICP-MS) to determine the platination state of the proteins. Consistent with the accumulation studies, pyriplatin bound to proteins in far greater amounts than enpyriplatin, and this study also revealed some different protein targets between the bifunctional cisplatin and monofunctional pyriplatin. This study highlights the need for more sophisticated techniques, such as SEC-ICP-MS, to determine not only how much of a platinum complex accumulates in cells, but also the speciation and metabolites of platinum anticancer drugs.

    更新日期:2017-12-14
  • Relationship between aluminum stress and caffeine biosynthesis in suspension cells of Coffea arabica L
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-07-29
    Roberto Pech-Kú, J. Armando Muñoz-Sánchez, Miriam Monforte-González, Felipe Vázquez-Flota, Beatriz A. Rodas-Junco, Víctor M. González-Mendoza, S.M. Teresa Hernández-Sotomayor

    Toxicity by aluminum is a growth-limiting factor in plants cultivated in acidic soils. This metal also promotes signal transduction pathways leading to the biosynthesis of defense compounds, including secondary metabolites. In this study, we observed that Coffea arabica L. cells that were kept in the dark did not produce detectable levels of caffeine. However, irradiation with light and supplementation of the culture medium with theobromine were the best conditions for cell maintenance to investigate the role of aluminum in caffeine biosynthesis. The addition of theobromine to the cells did not cause any changes to cell growth and was useful for the bioconversion of theobromine to caffeine. During a short-term AlCl3-treatment (500 μM) of C. arabica cells kept under light irradiation, increases in the caffeine levels in samples that were recovered from both the cells and culture media were evident. This augmentation coincided with increases in the enzyme activity of caffeine synthase (CS) and the transcript level of the gene encoding this enzyme (CS). Together, these results suggest that actions by Al and theobromine on the same pathway lead to the induction of caffeine biosynthesis.

    更新日期:2017-12-14
  • Characterizing activation mechanisms and binding preferences of ruthenium metallo-prodrugs by a competitive binding assay
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-07-16
    Christian Artner, Hannah U. Holtkamp, Christian G. Hartinger, Samuel M. Meier-Menches

    The activation mechanisms and reactivity of ruthenium metallo-prodrug lead structures were investigated in detail using capillary zone electrophoresis mass spectrometry (CZE–MS) in a time-dependent manner and by exposing to a protein/oligonucleotide mixture. The competitive assays were performed with sodium trans-[RuCl4(HInd)2] where Hind = indazole (NKP-1339), [(η6-p-cymene)RuCl2(pta)], where pta = 1,3,5-triaza-7-phosphaadamantane (RAPTA-C) and [(η6-biphenyl)RuCl(1,2-ethylenediamine)]PF6 (RM175). Molecular and quantitative information on binding preferences was obtained by coupling CZE to electrospray ionization MS (ESI-MS) and inductively coupled plasma MS (ICP-MS), respectively. A score system is presented that ranks the binding preferences of Ru complexes with nucleotides and demonstrated the following trend of decreasing selectivity after 24 h: RM175 (0.89) > RAPTA-C (0.78) > NKP-1339 (0.40). As expected, the organometallic drug candidates RM175 and RAPTA-C underwent a halido/aqua ligand exchange reaction at the metal center and showed distinct reactivity towards the biomolecules. In particular, the protein/DNA binding sites of RAPTA-C in a mixture of protein (ubiquitin) and oligonucleotide (5′-dATTGGCAC-3′) were located at single-amino acid and single-nucleotide resolution, respectively. Activated RAPTA-C bound selectively to Met1, adenine and cytosine in this setting, which contrasts with the selectivity of RM175 for guanine. Finally, activation products of NKP-1339 were detected corresponding to RuII(Hind)2 fragments coordinated to the oligonucleotide, which represents one of the few examples of a directly observed RuII adduct.

    更新日期:2017-12-14
  • Synthesis and anti-diabetic activity of new N,N-dimethylphenylenediamine-derivatized nitrilotriacetic acid vanadyl complexes
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-07-08
    Xia Niu, Jichun Yang, Xiaoda Yang

    Vanadium compounds are promising anti-diabetic agents. However, reducing the metal toxicity while keeping/improving the hypoglycemic effect is still a big challenge towards the success of anti-diabetic vanadium drugs. To improve the therapeutic potency using the anti-oxidative strategy, we synthesized new N,N-dimethylphenylenediamine (DMPD)-derivatized nitrilotriacetic acid vanadyl complexes ([VO(dmada)]). The in vitro biological evaluations revealed that the DMPD-derivatized complexes showed improved antioxidant capacity and lowered cytotoxicity on HK-2 cells than bis(maltolato)oxidovanadium (IV) (BMOV). In type II diabetic mice, [VO(p-dmada)] (0.15 mmol kg− 1/day) exhibited better hypoglycemic effects than BMOV especially on improving glucose tolerance and alleviating the hyperglycemia-induced liver damage. These insulin enhancement effects were associated with increased expression of peroxisome proliferator-activated receptor α and γ (PPARα/γ) in fat, activation of Akt (v-Akt murine thymoma viral oncogene)/PKB (protein kinase-B) in fat and liver, and inactivation of c-Jun NH2-terminal protein kinases (JNK) in liver. Moreover, [VO(p-dmada)] showed no tissue toxicity at the therapeutic dose in diabetic mice and the oral acute toxicity (LD50) was determined to be 1640 mg kg− 1. Overall, the experimental results indicated that [VO(p-dmada)] can be a potent insulin enhancement agent with improved efficacy-over- toxicity index for further drug development. In addition, the results on brain Tau phosphorylation suggested necessary investigation on the effects of vanadyl complexes on the pathology of the Alzheimer's disease in the future.

    更新日期:2017-12-14
  • Tumor cell uptake and selectivity of gadolinium(III)-phosphonium complexes: The role of delocalisation at the phosphonium centre
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-07-05
    Madleen Busse, Madeline S.A. Windsor, Alexander J. Tefay, Mingyue Kardashinsky, Jacob M. Fenton, Daniel E. Morrison, Hugh H. Harris, Louis M. Rendina

    The synthesis of a series of bifunctional Gd(III) complexes 1–3 covalently bound to arylphosphonium cations possessing a varying degree of delocalisation at the phosphonium centre is presented. The influence of the degree of delocalisation was investigated with regards to in vitro cytotoxicity, cellular uptake of Gd, tumor-cell selectivity and intracellular localisation of Gd within human glioblastoma (T98G) and human glial (SVG p12) cells. Cellular uptake and selectivity studies for the Gd(III) complexes indicate that a reduced delocalisation at the phosphonium centre can lead to an enhanced Gd uptake into SVG p12 cells which results in a decrease in the overall tumor cell selectivity. Synchrotron X-ray fluorescence (microbeam XRF) imaging has demonstrated for the first time that uniform uptake of Gd(III) complex 2 within a population of T98G cells increased as a function of increasing Gd incubation times. The Gd maps show dispersed spots of high intensity which are consistent with mitochondrial uptake.

    更新日期:2017-12-14
  • Copper-based reactions in analyte-responsive fluorescent probes for biological applications
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-07-04
    Ho Yu Au-Yeung, Chung Ying Chan, Ka Yan Tong, Zuo Hang Yu

    Copper chemistry has been capitalized on in a wide spectrum of biological events. The central importance of copper in biology lies in the diverse chemical reactivity of the redox-active transition metal ranging from electron transfer, small molecule binding and activation, to catalysis. In addition to its many different roles in natural biological systems, the diverse chemical reactivity of copper also represents a rich opportunity and resource to develop synthetic bioanalytical tools for the study of biologically important species and molecules. In this mini-review, fluorescent probes featuring a specific copper-based chemical reaction to selectively detect a biologically relevant analyte will be discussed. In particular, fluorescent probes for sensing labile copper ions, amino acids and small reactive species will be highlighted. The chemical principles, advantages and limitations of the different types of copper-mediated chemical reactions in these fluorescent probes will be emphasized.

    更新日期:2017-12-14
  • High resolution crystal structure of a fluoride-inhibited organophosphate-degrading metallohydrolase
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-06-27
    Christopher Selleck, Luke W. Guddat, David L. Ollis, Gerhard Schenk, Marcelo Monteiro Pedroso

    Metal ion-dependent, organophosphate-degrading enzymes (OP hydrolases) have received increasing attention due to their ability to degrade and thus detoxify commonly used pesticides and nerve agents such as sarin and VX. These enzymes thus garner strong potential as bioremediators. The OP hydrolase from Agrobacterium radiobacter (OpdA) is one of the most efficient members of this group of enzymes. Previous studies have indicated that the choice of the hydrolysis-initiating nucleophile may depend on the pH of the reaction, with a metal ion-bridging hydroxide being preferred at lower pH (i.e. pH ≤ 8.5), and a terminally coordinated hydroxide at higher pH (i.e. pH > 9.0). Furthermore, fluoride was shown to be a potent inhibitor of the reaction, but only at low pH. Here, the crystal structure (1.3 Å, pH 6) of OpdA in presence of fluoride is described. While the first coordination sphere in the active site displays minimal changes in the presence of fluoride, the hydrogen bonding network that connects the dimetallic metal center to the substrate binding pocket is disrupted. Thus, the structure of fluoride-inhibited OpdA demonstrates the significance of this hydrogen bond network in controlling the mechanism and function of this enzyme.

    更新日期:2017-12-14
  • Recent development of transition metal complexes with in vivo antitumor activity
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-06-16
    Jia-Xin Liang, Hai-Jing Zhong, Guanjun Yang, Kasipandi Vellaisamy, Dik-Lung Ma, Chung-Hang Leung

    The often severe side effects displayed by currently used platinum and ruthenium complexes have motivated researchers to design and develop transition metal-based anti-tumor agents with reduced toxicity. Distinct from organic anti-tumor drugs, transition metal complexes possess several properties that render them as promising scaffolds for anti-cancer drug discovery. While a vast number of metal complexes have been synthesized and reported to be promising and potent in vitro anticancer active compounds, fewer have shown efficacy in in vivo models. The demonstration of in vivo potency is an essential step for lead candidates for clinical trials. In this review, we highlight examples of transition metal-based complexes that have shown in vivo anti-tumor activities that have been described in recent years.

    更新日期:2017-12-14
  • Structural influences on the activity of bismuth(III) indole-carboxylato complexes towards Helicobacter pylori and Leishmania
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-05-31
    Amita Pathak, Victoria L. Blair, Richard L. Ferrero, Lukasz Kedzierski, Philip C. Andrews

    Seven new bismuth(III) complexes derived from indole-carboxylic acids have been synthesised: five are homoleptic; [Bi(IAA)3] B1, [Bi(IPA)3] B2, [Bi(IBA)3] B3, [Bi(MICA)3] B4, [Bi(IGA)3] B6, and two are heteroleptic [BiPh(MICA)2] B5 (where IAA-H = 2-(1H-indol-3-yl)acetic acid, IPA-H = 3-(1H-indol-3-yl)propanoic acid, IBA-H = 4-(1H-indol-3-yl)butanoic acid, IGA-H = 2-(1H-indol-3-yl)-2-oxoacetic acid, and MICA-H = 1-methyl-1H-indole-3-carboxylic acid). All complexes were fully characterised by elemental analysis, infrared and mass-spectroscopy, and nuclear magnetic resonance (1H, 13C) spectroscopy. Complex [BiPh(IGA)2] B7 is structurally authenticated by X-ray crystallography as a dimer in the solid-state. The in-vitro anti-bacterial activity of the indole-carboxylic acids and their bismuth(III) complexes was assessed against Helicobacter pylori. While the acids were non-toxic at < 100 μg mL− 1, all the bismuth compounds showed an MIC of 6.25 μg mL− 1, indicating that the anti-bacterial activity is insensitive to the degree of substitution at the Bi(III) centre or the composition of the indole-carboxylate ligands. All compounds were further tested for their anti-parasitic activity against Leishmania major and for their toxicity towards mammalian cells. From the anti-parasitic studies, it was found that the heteroleptic bismuth(III) complexes are the most active, with B5 and B7 showing comparable activity to Amphotericin B, without any toxicity towards the mammalian cells at their effective concentration.

    更新日期:2017-12-14
  • Controlled self-assembling structures of ferrocene-dipeptide conjugates composed of Ala-Pro-NHCH2CH2SH chain
    J. Inorg. Biochem. (IF 3.348) Pub Date : 2017-05-18
    Toshiyuki Moriuchi, Taiki Nishiyama, Yoshiki Tayano, Toshikazu Hirao

    Bioorganometallic ferrocene-dipeptide conjugates with the Ala-Pro-cysteamine chain, Fc-L-Ala-L-Pro-NHCH2CH2SH (2) and Fc-L-Ala-D-Pro-NHCH2CH2SH (4) (Fc = ferrocenoyl), were prepared by the reduction of the ferrocene-dipeptide conjugates, Fc-L-Ala-L-Pro-cystamine-L-Pro-L-Ala-Fc (1) or Fc-L-Ala-D-Pro-cystamine-D-Pro-L-Ala-Fc (3), respectively. Control of the self-assembling structures of the ferrocene-dipeptide conjugates was demonstrated by changing the chirality of the amino acid. The molecular structure of 2 composed of the L-Ala-L-Pro-NHCH2CH2SH chain confirmed the formation of intramolecular hydrogen bond of N-H ⋯ N pattern between the NH of cysteamine moiety and the nitrogen of Pro moiety. Furthermore, intermolecular hydrogen bonds between NH (Ala) and CO (Pro of another molecule) and between NH (cysteamine) and CO (the ferrocenoyl moiety of another molecule) were formed, wherein each molecule is connected to four neighboring molecules by continuous intermolecular hydrogen bonds to form the hydrogen-bonded molecular assembling structure. On the contrary, the left-handed helical assembly through an intermolecular hydrogen-bonding network of 15-membered intermolecularly hydrogen-bonded ring between NH (Ala) and CO (the ferrocenoyl moiety of another molecule) and between NH (the cysteamine moiety of another molecule) and CO (Ala) was observed in the crystal packing of 4 composed of the L-Ala-D-Pro-NHCH2CH2SH chain.

    更新日期:2017-12-14
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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