1,721,073 research outputs found

    Complex Formation of Lead(II) with Nucleotides and Their Constituents

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    Lead is widely distributed in the environment; it is known to mankind for thousands of years and its toxicity is nowadays (again) well recognized, though on the molecular level only partly understood. One of the reasons for this shortcoming is that the coordination chemistry of the biologically important lead(II) is complicated due to the various coordination numbers it can adopt (CN = 4 to 10) as well as by the 6s² electron lone pair which, with CN = 4, can shield one side of the Pb²⁺ coordination sphere. The chapter focuses on the properties of Pb²⁺ complexes formed with nucleotides and their constituents and derivatives. Covered are (among others) the complexes formed with hydroxy groups and sugar residues, the interactions with the various nucleobases occurring in nucleic acids, as well as complexes of phosphates. It is expeced that such interactions, next to those like with lipids and proteins, are responsible for the toxic properties of lead. To emphasize the special properties of Pb²⁺ complexes, these are compared as far as possible with the corresponding properties of the Ca²⁺, Fe²⁺, Cu²⁺, Zn²⁺, and Cd²⁺ species. It needs to be mentioned that the hard-soft rule fails with Pb²⁺. This metal ion forms complexes with ligands offering O donors of a stability comparable to that of Cu²⁺. In contrast, with aromatic N ligands, like imidazole or N7 sites of purines, complex stability is comparable to that of the corresponding Fe²⁺ complexes. The properties of Pb²⁺ towards S donor sites are difficult to generalize: On the one hand Pb²⁺ forms very stable complexes with nucleoside 5′-O-thiomonophosphates by coordinating to nearly 100% at S in the thiophosphate group; however, on the other hand, once a sulfur atom replaces one of the terminal oxygen atoms in the phosphodiester linkage, macrochelate formation of the phosphate-bound Pb²⁺ occurs with the O and not the S site. Quite generally, the phosphodiester linkage is a relatively weak binding site, but the affinity increases further to the mono-and then to the di-and triphosphate. The same holds for the corresponding nucleotides, though the Pb²⁺ affinity had to be estimated via that of the Cu²⁺ complexes for some of these ligands. Complex stability of the pyrimidine-nucleotides (due to their anti conformation) is solely determined by the coordinating tendency of the phosphate group(s); this also holds for the Pb²⁺ complex of adenosine 5′-monophosphate. For the other purinenucleotides macrochelate formation takes place by the interaction of the phosphate-coordinated Pb²⁺ with the N7/(C6)O site of, e.g., the guanine residue. The extents of the formation degrees of these chelates are summarized. Unfortunately, information about mixed ligand (ternary) or other higher order comlexes is missing, but still it is hoped that the present overview will help to understand the interaction of Pb²⁺ with nucleotides and nucleic acids, and especially that it will facilitate further research in this fascinating area

    Metallo-drugs: development and action of anticancer agents/ edited by Astrid Sigel, Helmut Sigel, Eva Freisinger, and Roland K.O. Sigel.

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    In English.Includes bibliographical references and index.Volume 18 centers on biological, medicinal inorganic chemistry. The serendipitous discovery of the antitumor activity of cis-diamminodichloroplatinum(II) (cisplatin) by Barnett Rosenberg in the 1960s is a landmark in metallodrug-based chemotherapy. The success of cisplatin in the clinic, followed by oxaliplatin and carboplatin, along with their drawbacks relating mainly to resistance development and severe toxicity, initiated research on polynuclear platinum complexes and on Pt(IV) complexes as prodrugs. Furthermore, the indicated shortcomings led to the exploration of other transition and main group metal ions, among them Ru(II/III), Au(I/III), Ti(IV), V(IV/V), and Ga(III) including also the essential metal ions Fe(II/III), Cu(I/II), and Zn(II). Ionic as well as covalent and non-covalent interactions between structurally very different complexes and biomolecules like nucleic acids, proteins, and carbohydrates are studied and discussed with regard to their possible anticancer actions. Hence, MILS-18 summarizes the research at the forefront of medicinal inorganic chemistry, including studies on the next-generation, tailor-made anticancer drugs. All this and more is treated in an authoritative and timely manner in the 17 stimulating chapters of this book, written by 39 internationally recognized experts from 10 nations (from the US via Europe to China and Australia). The impact of this vibrant research area is manifested by more than 2700 references, nearly 150 illustrations (more than half in color) and several comprehensive tables. Metallo-Drugs: Development and Action of Anticancer Agents is an essential resource for scientists working in the wide range from enzymology, material sciences, analytical, organic, and inorganic biochemistry all the way through to medicine including the clinic ... not forgetting that it also provides excellent information for teaching.About the editors -- Historical development and perspectives of the series / Preface to volume 18 / Contributors to volume 18. -- 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. Subject index. Astrid Sigel, Helmut Sigel, Roland K.O. Sigel -- Astrid Sigel, Helmut Sigel, Eva Freisinger, Roland K.O. Sigel -- Imogen A. Riddell, Stephen J. Lippard -- Viktor Brabec, Jana Kasparkova, Vijay Menon, Nicholas P. Farrell -- V. Venkatesh, Peter J. Sadler -- Nicholas P. Farrell, Anil K. Gorle, Erica J. Peterson, Susan J. Berners-Price -- Enzo Alessio, Luigi Messori -- Maria V. Babak, Wee Han Ang -- Angela Casini, Raymond Wai-Yin Sun, Ingo Ott -- Edit Y. Tshuva, Maya Miller -- Debbie C. Crans, Lining Yang, Allison Haase, Xiaogai Yang -- Christopher R. Chitambar -- Lucia Cardo, Michael J. Lucia -- Ramon Vilar -- Matthew P. Sullivan, Hannah U. Holtkamp, Christian G. Hartinger -- Ulrich Schatzschneider -- Frank Thévenod -- Delphine Denoyer, Sharnel A.S. Clatworthy, Michael A. Cater -- Silvia Ziliotto, Olivia Ogle,Kathryn M. Taylor -- Cisplatin and oxaliplatin : our current understanding of their actions / Polynuclear platinum complexes : structural diversity and DNA binding / Platinum(IV) prodrugs / Metalloglycomics / The deceptively similar ruthenium(III) drug candidates KP1019 and NAMI-A have different actions : what did we learn in the past 30 years? / Multinuclear organometallic ruthenium-arene complexes for cancer therapy / Medicinal chemistry of gold anticancer metallodrugs / Coordination complexes of titanium(IV) for anticancer therapy / Health benefits of vanadium and its potential as an anticancer agent / Gallium complexes as anticancer drugs / Non-covalent metallo-drugs : using shape to target DNA and RNA junctions and other nucleic acid structures / Nucleic acid quadruplexes and metallo-drugs / Antitumor metallodrugs that target proteins / Metallointercalators and metalloinsertors : structural requirements for DNA recognition and anticancer activity / Iron and its role in cancer defense : a double-edged sword / Copper complexes in cancer therapy / Targeting zinc(II) signalling to prevent cancer /1 online resource (588 pages

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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