Two New Ternary Complexes of Copper(II) with Tetracycline or Doxycycline and 1,10-Phenanthroline and Their Potential as Antitumoral: Cytotoxicity and DNA Cleavage

This paper reports on the synthesis and characterization of two new ternary copper(II) complexes: [Cu(doxy-cycline)(1,10-phenanthroline)(H(2)O)(ClO(4))](ClO(4)) (1) and [Cu(tetracycline)(1,10-phenanthroline)(H(2)O)(ClO(4))](ClO(4)) (2). These compounds exhibit a distorted tetragonal geometry around copper, which is coordinated to two bidentate ligands, 1,10-phenanthroline and tetracycline or doxycyline, a water molecule, and a perchlorate ion weakly bonded in the axial positions. In both compounds, copper(II) binds to tetracyclines`. via the oxygen of the hydroxyl group and oxygen of the amide group at ring A and to 1,10-phenanthroline via its two heterocyclic nitrogens. We have evaluated the binding of the new complexes to DNA, their capacity to cleave it, their cytotoxic activity, and uptake in tumoral cells. The complexes bind to DNA preferentially by the major groove, and then cleave its strands by an oxidative mechanism involving the generation of ROS. The cleavage of DNA was inhibited by radical inhibitors and/or trappers such as superoxide dismutase, DMSO, and the copper(I) chelator bathocuproine. The enzyme T4 DNA ligase was not able to relegate the products of DNA cleavage, which indicates that the cleavage does not occur via a hydrolytic mechanism. Both complexes present an expressive plasmid DNA cleavage activity generating single- and double-strand breaks, under mild reaction conditions, and even in the absence of any additional oxidant or reducing agent. In the same experimental conditions, [Cu(phen)(2)](2+) is approximately 100-fold less active than our complexes. These complexes are among the most potent DNA cleavage agents reported so far. Both complexes inhibit the growth of K562 cells With the IC(50) values of 1.93 and 2.59 mu mol L(-1) for compounds I and 2, respectively. The complexes are more active than the free ligands, and their cytotoxic activity correlates with intracellular copper concentration and the number of Cu-DNA adducts formed inside cells.

Raman, IR, UV-vis and EPR characterization of two copper dioxolene complexes derived from L-dopa and dopamine

The anionic complexes [Cu(L(1-))(3)](1-), L(-) = dopasemiquinone or L-dopasemiqui none, were prepared and characterized. The complexes are stable in aqueous solution showing intense absorption bands at ca. 605 nm for Cu(II)-L-dopasemiquinone and at ca. 595 nm for Cu(II)-dopasemiquinone in the UV-vis spectra, that can be assigned to intraligand transitions. Noradrenaline and adrenaline, under the same reaction conditions, did not yield Cu-complexes, despite the bands in the UV region showing that noradrenaline and adrenaline were oxidized during the process. The complexes display a resonance Raman effect, and the most enhanced bands involve ring modes and particularly the vCC + vCO stretching mode at ca. 1384 cm(-1). The free radical nature of the ligands and the oxidation state of the Cu(II) were confirmed by the EPR spectra that display absorptions assigned to organic radicals with g= 2.0005 and g = 2.0923, and for Cu(II) with g = 2.008 and g = 2.0897 for L-dopasemiquinone and dopasemiquinone, respectively. The possibility that dopamine and L-dopa can form stable and aqueous-soluble copper complexes at neutral pH, whereas noradrenaline and adrenaline cannot, may be important in understanding how Cu(II)-dopamine crosses the cellular membrane as proposed in the literature to explain the role of copper in Wilson disease. (c) 2008 Elsevier B.V. All rights reserved.

Electroluminescent devices based on rare-earth tetrakis beta-diketonate complexes

In this paper the synthesis, photo luminescence and electroluminescence investigation of the novel tetrakis beta-diketonate of rare-earth complexes such as M[Eu(dbM)(4)] and M[Tb(acac)(4)] with a variety of cationic ligands, M=Li(+), Na(+) and K(+) have been investigated. The emission spectra of the Eu(3+) and Tb(3+) complexes displayed characteristic narrow bands arising from intraconfigurational transitions of trivalent rare-earth ions and exhibited red color emission for the Eu(3+) ion ((5)D(0) -> F(J), J=0-6) and green for the Tb(3+) ion ((5)D(4) -> (7)F(J), J = 6-0). The lack of the broaden emission bands arising from the ligands suggests the efficient intramolecular energy transfer from the dbm and acac ligands to Eu(3+) and Tb(3+) ions, respectively. In accordance to the expected, the values of PL quantum efficiency (eta) of the emitting (5)D(0) state of the tetrakis(beta-diketonate) complexes of Eu(3+) were higher compared with those tris-complexes. Therefore, organic electroluminescent (EL) devices were fabricated with the structure as follows: indium tin oxide (ITO)/hole transport layer (HTL) NPB or MTCD/emitter layer M[RE(beta-diketonate)(4)] complexes)/Aluminum (Al). All the films were deposited by thermal evaporation carried out in a high vacuum environment system. The OLED light emission was independent of driving voltage, indicating that the combination of charge carriers generates excitons within the M[RE(beta-diketonate)(4)] layers, and the energy is efficiently transferred to RE(3+) ion. As a best result, a pure red and green electroluminescent emission was observed from the Eu(3+) and Tb(3+) devices, confirmed by (X,Y) color coordinates. (C) 2008 Elsevier B.V. All rights reserved.

Synthesis, Structural Characterization, and Biological Evaluation of Oxorhenium(V) Complexes with a Novel Type of Thiosemicarbazones Derived from N-[N `,N `-Dialkylamino(thiocarbonyl)]benzimidoyl Chlorides

Reactions of N-[N`,N`-diethylamino(thiocarbonyl)]benzimidoyl chloride with 4,4-dialkylthiosemicarbazides give a novel class of thiosemicarbazides/thiosemicarbazones, H(2)L, which causes a remarkable reduction of cell growth in in vitro experiments. These strong antiproliferative effects are also observed for oxorhenium(V) complexes of the general composition [ReOCl(L)], which are formed by reactions of the potentially tridentate ligands with (NBu(4))[ReOCl(4)]. A systematic substitution of the alkyl groups in the thiosemicarbazone building blocks of the ligands do not significantly influence the biological activity of the metal complexes, while the replacement of the chloro ligand by a PPh(3) ligand (by the replacement of the oxo unit by a nitrido ligand) completely terminated the cytotoxicity of the metal complexes.

Mixed-Ligand Complexes of Technetium and Rhenium with Tridentate Benzamidines and Bidentate Benzoylthioureas

Mixed-ligand complexes of technetium(V) or rhenium(V) containing tridentate N-[(dialkylamino)(thiocarbonyl)]benzamidine (H(2)L(1)) and bidentate N,N-dialkyl-N`-benzoylthiourea (HL(2)) ligands were formed in high yields when (NBu(4))[MOCl(4)] (M = Tc or Re) or [ReOCl(3)(PPh(3))(2)] was treated with mixtures of the proligands. Other approaches for the synthesis of the products are reactions of [MOCl(L(1))] complexes with HL(2) or compounds of the-composition [ReOCl(2)(PPh(3))(L(2))] with H(2)L(1). The resulting air-stable [MO(L(1))(L(2))] complexes possess potential for the development of metal-based radiopharmaceuticals. [TcO(L(1))(L(2))] complexes are readily reduced by PPh3 with formation of [Tc(L(1))(L(2))(PPh(3))]. The resulting Tc(III) complexes undergo two almost-reversible oxidation steps corresponding to one-electron transfer processes. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Oxotechnetium(V) Complexes with a Novel Class of Tridentate Thiosemicarbazide Ligands

A novel tridentate thiosemicarbazide-type ligand class with an SNS donor set, H(2)L(1), was prepared by reactions of N-[N`,N`-dialkylamino(thiocarbonyl)]benzimidoyl chlorides with thiosemicarbazides. H(2)L(1) ligands readily react with (NBu(4))[TcOCl(4)] in MeOH under the formation of red oxotechnetium(V) complexes of composition [TcOCl(L(1))]. The monomeric, five-coordinate compounds are air-stable and bind (L(1))(2-) tridentate in the equatorial coordination sphere. The compounds represent the first examples of oxotechnetium(V) complexes with NS chelate-bonded thiosemicarbazones.

Kvalitetsuppföljningar och sjuksköterskans omvårdnadsprioriteringar i särskilt boende : En kvalitativ intervjustudie

Syfte: Att undersöka hur sjuksköterskor inom särskilt boende resonerar kring kvalitetsuppföljningar och dess eventuella konsekvenser för omvårdnaden. Metod: Semistrukturerade intervjuer efter öppen intervjuguide med sex sjuksköterskor. Kvalitativ innehållsanalys enligt Graneheim och Lundmans metod. Huvudresultat: I vilken grad kvalitetsregistren och kvalitetsuppföljningarna integreras i omvårdnadsarbetet och dess utveckling är centralt för om dessa uppfattas som stöd eller hinder för god kvalité i omvårdnaden. Dubbel dokumentation bidrar till att sjuksköterskorna omprioriterar arbetstiden och arbetar mer konsultativt och administrativt. Detta minskar tiden för omvårdnadsobservationer och handleding av omvårdnadspersonal samt gör att kvalitetsregistreringar snarast uppfattas som ett hinder. Sjuksköterskorna använde sin professionella kunskap och kliniska erfarenhet i högre grad än registerdata vid omvårdnadsbedömningar. Dessa sågs som alltför komplexa för att kunna fångas i kryssfrågeformulär. Mer kliniska observationer efterfrågas i kvalitetsuppföljningarna för ökad medvetenhet om hög arbetsbelastning och dess eventuella konsekvenser samt för att garantera de boende god omvårdnadskvalité. Konklusion: Sjuksköterskorna upplever att de arbetar under svår tidspress. Tiden anges som essentiell för vilken omvårdnadskvalité som erbjuds. Vid beslut om registreringar av kvalitetsindikatorer bör sjuksköterskornas totala arbetsbörda beaktas. Registreringarna bör integreras i befintliga journalsystem så att sjuksköterskornas omprioriteringar inte får negativa konsekvenser för omvårdnadskvaliten.

För Sverige i framtiden : Bio-objektifiering av ny medicinsk teknologi

Taking Sweden into the future – Bio-objectification of new medical technology In this article, we analyze how contemporary discursive silences around new biotechnologies such as cybrids and induced pluripotent stem cells (iPSC), have been enabled by earlier policy processes in the area, e.g. boundary work around what is human and non-human, living and non-living, subject and object. The analysis of policy processes around xenotransplantations and the use of human embryonic stem cells, shows that the stem cells’ and xenografts’ “bio-identities” become stabilized through high expectations for the future, a lack of therapeutic possibilities and struggles over definitions of life. The policy processes around human embryonic stem cells and organs from other animals, are characterized by a normalization of certain understandings of ”life”, trust in scientific progress and it’s national financial potentials and a categorization of criticism as irrational. Through these “bio-objectification processes”, debate and decision making has been moved from a political and public context into ethical committees and research funding bodies. The article concludes by discussing consequences of this political non-handling of biomedical technologies and how these bioobjects could be re-politicized.

Europeisk familjelycka : Om användandet av familjemetaforen i EU

The re-unification of a family of nations: usages of the family metaphor in the EU This article analyses usages of the family metaphor in the EU. It starts up with a scrutiny of feminist theories of the nation-as-family metaphor. Introducing the concept of domopolitics, the author infers that the family, on the one hand, connotes to feelings of security and homelyness and, on the other hand, fears of the well-known, of immanent threats to in-group cohesion. The significance of the family metaphor in the EU rhetoric connects to a renewed emphasis on distinct values, principles and norms that balance the otherwise technocratic image of the EU. He further applies the nation-as-family metaphor to contemporary EU rhetoric. In the analysis, he infers that all three dimensions of the metaphor (ethnic, civil and hierarchic) are manifest in the EU political language making its use an enterprise that strives at moving beyond, but not completely away from the nation-state paradigm.

Tillhörighetens gränser : Internationell adoption och ursprungets betydelse i svensk utredningsretorik

Boundaries of belonging: transnational adoption and the significance of origin in Swedish official rhetoric This article explores how the category of ‘transnational adoptees’ in Sweden is constructed in two Official Government Reports (SOU). The article is inspired by poststructuralist perspectives on welfare and social categorization, and draws from a postcolonial and feminist theoretical framework. ‘Transnational adoptees’ as a category is understood as constituted through discourse, and given meaning in different contexts. In the reports, a fundamental importance is attached to the fact that individuals with a background as transnationally adopted have been separated from their birth family and country of birth. It is argued that mental problems and a split identity are consequences to be expected from the separation. (Re)connection to the origin is therefore considered to be crucial for the well-being of the group. The article concludes that this line of reasoning is based on a specific logic of blood and roots, in which ‘transnational adoptees’ are understood as belonging to their countries of birth, rather than Sweden. The logic of blood and roots can be read as a form of racialized othering, but also as a discursive exclusion of ‘transnational adoptees’ from Sweden as an imagined, national community.

Det är enklare i teorin… Om skolutveckling i praktiken : En fallstudie av ett skolutvecklingsprojekt i en gymnasieskola

This dissertation is a case study dealing with a school development project that took place in an upper secondary school as a result of a merger of two schools with different cultures. The project used a method called “Frirumsmodellen” and was planned to be conducted in three steps. The first was to carry out a cultural analysis in order to map the preconditions to start a school development project. The second was to carry out concrete actions and finally study eventual effects from such activities by doing a second cultural analysis. My role was to be a supervisor in the school development work, but at the same time study how this work was conducted and its impact in the ordinary school day. The dissertation takes its departure in the fact that schools are political governed. The mission of schools is never neutral; it is always an expression of behind laying social forces, ideologies and ideals of the contemporary society. Of this reason, there is a close connection between the macro political level and the micro political level. Another point of departure is the transition from a modern to a post modern society that gives the character to the changes that take place in schools. Steering of schools has partly been treated as a technical implementation problem. Schools contain on going conflicts between different interest groups that, more or less regularly, end up in educational reforms. These reforms generate school development activities in the single school. Undoubtedly, this makes school development to a complex process. At a rather late stage of the study I decided not to fulfil my task to follow the original plan. I instead let the school development project as a model to be in focus. The over all purpose was formulated: How is it possible to understand what happened in the school development project in the Falkgymnasiet and why was it not possible to carry it out as it was said in the project plan? To interpret what took place during the project I did create an interpretation frame of implementation and complexity theory that also made it possible to critically scrutinise the “Frirumsmodellen”. Already in an early stage of the process it was obvious that the “Frirumsmodellen” did not supply any tools to use and it became disconnected from the project. The project in it selves was marginalised and made invisible. The headmaster used the situation to change things she thought were important to develop. As a result, things happened, but most of the involved people did not at first hand connect this to the project. It is, of course, difficult in detail to say what caused what. The complexity theory successively made the hidden patterns revealed, hidden unofficial potentates visible, as well as unpredictable conditions that generated reactions from the personnel in front of a development work. Together this was rather efficient obstacles for not changing this school. I also discuss school development and implementation problems on a general level, for example, the possibility to transform a top-down initiated project to be bottom-up driven and using project as a tool for school development work. It was obvious that headmasters and teachers must be prepared to handle the ideological dimensions of problems schools have to face. Consequently, development work is about making problems visible and to handle these in the intersection point between the intentions of educational policies, pedagogical researchers, school administrators, headmasters, teachers and pupils. The ideological dimension also contains an existential issue. Do I as a teacher share the intentions for the development work? If not, how must I act?

Passive MVC och MVVM designmönster i Android : En jämförelse av kodkomplexitet mellan Passive MVC och MVVM

Det mobila operativsystemet Android är idag ett ganska dominerande operativsystem på den mobila marknaden dels på grund av sin öppenhet men också på grund av att tillgängligheten är stor i och med både billiga och dyra telefoner finns att tillgå. Men idag har Android inget fördefinierat designmönster vilket leder till att varje utvecklare får bestämma själv vad som ska användas, vilket ibland kan leda till onödigt komplex kod i applikationerna som sen blir svårtestad och svårhanterlig. Detta arbete ämnar jämföra två designmönster, Passive Model View Controller (PMVC) och Model View View-Model (MVVM), för att se vilket designmönster som blir minst komplext med hjälp av att räkna fram mätvärden med hjälp av Cyclomatic Complexity Number (CCN). Studien är gjord utifrån arbetssättet Design & Creation och ämnar bidra med: kunskap om vilket mönster man bör välja, samt om CCN kan peka ut vilka delar i en applikation som kommer att ta mer eller mindre lång tid att testa. Under studiens gång tog vi även fram skillnader på om man anväder sig av den så kallade Single Responsibilyt Principle (SRP) eller inte. Detta för att se om separerade vyer gör någon skillnad i applikationernas komplexitet. I slutändan så visar studien på att komplexiteten i små applikationer är väldigt likvärdig, men att man även på små applikationer kan se skillnad på hur komplex koden är men också att kodkomplexitet på metodnivå kan ge riktlinjer för testfall.

Double stranded DNA-binding studies of potential Rhodium(ll) antitumor complexes

In 1952, Dwyer and coworkers began testing a series of metal complexes for potential inhibition of cancer cell proliferation in animals.[l] The complexes tested were unsuitable for such studies due to their high toxicity. Therefore, no further work was done on the project. However, in 1965, Rosenberg and coworkers revisited the possibility of potential metal-based drugs. Serendipitously, they discovered that cis-diamminedichloroplatinum(lI) (cisplatin) inhibits cell division in E. coli.[2] Further studies of this and other platinum compounds revealed inhibition of tumor cell lines sarcoma 180 and leukemia LI2l0 in mice.[l] Cisplatin was approved by the Food and Drug Administration in 1970 as a chemical chemotherapeutic agent in the treatment of cancer. The drug has primarily been used in the treatment of testicular and ovarian cancers, although the powerful chemotherapeutic properties of the compound indicate use against a variety of other cancers.[3] The toxicity of this compound, however, warrants the development of other metal-based potential antitumor agents. The success of cisplatin, a transition-metal-based chemotherapeutic, opened the doors to a host of research on the antitumor effects of other transition-metal complexes. Beginning in the 1970s, researchers looked to rhodium for potential use in antitumor complexes. Dirhodium complexes with bridging equatorial ligands (Figure I) were the primary focus for this research. The overwhelming majority of these complexes were dirhodium(II) carboxylate complexes, containing two rhodium(II) centers, four equatorial ligands in a lantero formation around the metal center, and an axial ligand on either end. The family of complexes in Figure 1 will be referred to as dirhodium(II) carboxylate complexes. The dirhodium centers are each d? with a metal-metal bond between them. Although d? atoms are paramagnetic, the two unpaired electrons pair to make the complex diamagnetic. The basic formula of the dirhodium(lI) carboxylate complexes is Rh?(RCOO)?(L)? with R being methyl, ethyl, propyl, or butyl groups and L being water or the solvent in which the complex was crystalized. Of these dirbodium(II) carboxylate complexes, our research focuses on Rb la and two other similar complexes Rh2 and Rh3 (Figure 2). Rh2 is an activated form of Rhla, with four acetonitrile groups in place of two of the bidentate acetate ligands. Rh3 is similar to Rhla, with trifluoromethyl groups in place of the methyl groups on the acetate ligands.

Syntheses of Cross-Linking Agents, Molecular Modeling of Oligonucleotides and Polypeptide-Ion Complexes

Each section of this thesis will be subdivided into three parts encompassing all of the research in which I have been involved during the past three years. These will be referred to under the headings "Syntheses:' "Molecular Modeling," and "Cross-linking Efficiencies." Each of these subdivisions may have divisions within them when necessary in order to fully detail the research.

As relações acadêmicas de produção na pós-Graduação em administração no Brasil

A presente tese pretende contribuir criticamente para o entendimento das intrincadas relações existentes entre o Estado, o capital e a produção acadêmica. Para isso, se propôs a interpretar as relações acadêmicas de produção na pós-graduação em Administração no Brasil articulando-as com categorias analíticas mais amplas, delineadas de forma a fornecer um quadro, ao fundo, da economia-política. O pressuposto de que a atual intensificação dos ritmos de produção acadêmica contrasta com um passado – idealizado – de ciência contemplativa precisou ser confrontado com o desenvolvimento histórico da educação superior e da pós-graduação no país objetivando-se demover certas mitificações do debate. O Estado, em sua versão reformada a partir do ideário friedmaniano, o conceito de capital monopolista e a teoria do processo de trabalho forneceram suporte teórico-metodológico – e empírico – para a interpretação do quadro político-econômico proposto. Para a passagem do geral para o particular – das conexões entre o Estado e o capital à produção acadêmica – recorreu-se à coleta de dados em duas frentes: (i) analisou-se a produção acadêmica de todos os 168 pesquisadores-doutores bolsistas (até março de 2014) em Produtividade em Pesquisa (PQ) do CNPq na área de Administração e (ii) realizou-se entrevistas em profundidade com pesquisadores-doutores e doutorandos dos mais variados programas de pós-graduação em Administração do país. Os resultados foram inquietantes: verificou-se que está em curso um processo de intensificação da incorporação da mão-de-obra formada por alunos-orientandos às estruturas pedagógico-produtivas dos cursos de pós-graduação. Os orientandos respondem pela parcela mais substantiva do total da produção acadêmica, enquanto que os processos de trabalho aprofundam re-significações das atribuições dos cursos de pós-graduação e intensificam a divisão do trabalho, com impactos diversos nas relações entre os sujeitos da pós-graduação. Quando se procede ao movimento analítico inverso – das relações no interior da pós-graduação em Administração no Brasil para o quadro da economia-política posicionado ao fundo – observa-se que o Estado (principalmente através da CAPES e do CNPq) e o mercado capitalista acadêmico (tendendo a poucas empresas de capital monopolista) acrescentam determinações fundamentais às relações acadêmicas de produção. Índices de avaliação baseados em métricas de contabilidade da pesquisa se legitimam como monopólios epistemológicos da qualidade e se institucionalizam pelas ações coordenadas da CAPES e do CNPq no conjunto do sistema oficial de pós-graduação. Metas de produção são estabelecidas e re-significadas pelos sujeitos. No limite, define-se até mesmo o tipo de ciência que se produz na área. Conclui-se que a resistência aos atuais padrões intensificados de produção acadêmica passa pelo entendimento crítico de todas essas relações que se costuram e se estruturam no interior da pós-graduação.