Interaction with biomolecules and biological activity of metal complexes and silver atomic quantum clusters

En este trabajo se exploran los mecanismos a través de los cuales ejercen su actividad biológica compuestos de diversa naturaleza con potencial actividad anticancerígena. Este tipo de estudios constituyen las primeras etapas básicas en la investigación contra el cáncer, ya que tienen como objetivo fundamental entender qué factores son determinantes en la actividad biológica de los mismos, lo que permite avanzar en el diseño racional de nuevas drogas anticancerígenas que permitan enfrentarnos a los retos de mejorar de la eficacia de los tratamientos existentes, la supresión de los nocivos efectos secundarios inducidos por estas drogas y la superación de la resistencia adquirida a las mismas.In this work the mechanisms of biological action of different drugs with potential anticancer activity are explored. These studies constitute the first steps in the basic research against cancer, as they aim at understanding the key factors that determine the biological activity of these drugs. This information on the structure-activity relationship helps to develop a rational design of new drugs with improved efficacy that could let us overcome problems such as the severe side effects of classical antitumor agents and the acquired resistance to these treatments

Kinetic evidence for interaction of TMPyP4 with two different G-quadruplex conformations of human telomeric DNA

Background: Stabilization of G-quadruplex helices by small ligands has attracted growing attention because they inhibit the activity of the enzyme telomerase, which is overexpressed in> 80% cancer cells. TMPyP4, one of the most studied G-quadruplex ligands, is used as a model to show that the ligands can exhibit different binding features with different conformations of a human telomeric specific sequence. Methods: UV–Vis, FRET melting Assay, Isothermal Titration Calorimetry, Time-resolved Fluorescence lifetime, T-Jump and Molecular Dynamics. Results: TMPyP4 yields two different complexes with two Tel22 telomeric conformations in the presence of Na+ or K+. T-Jump kinetic experiments show that the rates of formation and dissociation of these complexes in the ms time scale differ by one order of magnitude. MD simulations reveal that, in K+ buffer, “hybrid 1” conformation yields kinetic constants on interaction with TMPyP4 one order lower than “hybrid 2”. The binding involves π–π stacking with external loop bases. Conclusions: For the first time we show that for a particular buffer TMPyP4 interacts in a kinetically different way with the two Tel22 conformations even if the complexes formed are thermodynamically indistinguishable. General significance: G-quadruplexes, endowed with technological applications and potential impact on regulation mechanisms, define a new research field. The possibility of building different conformations from same sequence is a complex issue that confers G-quadruplexes very interesting features. The obtaining of reliable kinetic data constitutes an efficient tool to determine reaction mechanisms between conformations and small molecules.“la Caixa” Foundation (project OSLC-2012-007), MINECO, (CTQ2014- 58812-C2-2-R) and Junta de Castilla y León, (BU042U16), FEDER Funds Spai

Binding studies of metal–salphen and metal–bipyridine complexes towards G‐Quadruplex DNA

The proposed in vivo formation of G-quadruplex DNA (G4 DNA) in promoter regions of oncogenes and in telomeres has prompted the development of small molecules with high affinity and selectivity for these structures. Herein we report the synthesis of a new di-substituted bipyridine ligand and the corresponding complexes with Ni2+ and VO2+. Both these new complexes have been characterized spectroscopically and by X-ray crystallography. Detailed DNA binding studies of these two complexes, together with three previously reported metal salphen complexes, are presented. Using FRET melting assays, the binding affinity and selectivity of the five metal complexes against six different G4 DNA structures as well as a duplex DNA have been determined. In addition, we present detailed ITC and UV/Vis studies to characterize the interaction of the complexes with human telomeric G4 DNA. Finally, we show via a polymerase stop assay that these complexes are able to stabilize a G4 DNA structure (from the c-Myc oncogene promoter) and halt the activity of Taq polymerase.UK’s Engineering and Physical Sciences Research Council (EPSRC) (grant number: EP/H005285/1

Biological activity and photocatalytic properties of a naphthyl-imidazo phenanthroline (HNAIP) ligand and its [Ir(ppy)2(HNAIP)]Cl and [Rh(ppy)2(HNAIP)]Cl complexes

The synthesized 2-(hydroxy-1-naphtyl)imidazo-[4,5-f][1,10]phenanthroline (HNAIP) ligand and its new iridium ([Ir(ppy)2(HNAIP)]Cl) and rhodium ([Rh(ppy)2(HNAIP)]Cl) complexes, being ppy = 2-phenylpiridinate, show cytotoxic effects in SW480 (colon adenocarcinoma) and A549 (epithelial lung adenocarcinoma) cells. They all are cytotoxic in the tested cell lines. HNAIP and [Rh(ppy)2(HNAIP)]+ are the most cytotoxic, whereas [Ir(ppy)2(HNAIP)]+ displays negligible cytotoxicity towards A549 cells and moderate activity towards SW480. The interaction of all three compounds with Bovine Serum Albumin (BSA), l-glutathione reduced (GSH), nicotinamide adenine dinucleotide (NADH) and DNA was studied to explain the differences found in terms of cytotoxicity. None of them are able to interact with BSA, thus excluding bioavailability due to plasma protein interaction as the possible differentiating factor in their biological activity. By contrast, small differences have been observed regarding DNA interaction. In addition, taking advantage of the emission properties of these molecules, they have been visualized in the cytoplasmic region of A549 cells. Inductively coupled plasma mass spectrometry (ICP-MS) experiments show, in turn, that the internalization ability follow the sequence [Rh(ppy)2(HNAIP)]+ > [Ir(ppy)2(HNAIP)]+ > cisplatin. Therefore, it seems clear that the cellular uptake by tumour cells is the key factor affecting the different cytotoxicity of the metal complexes and that this cellular uptake is influenced by the hydrophobicity of the studied complexes. On the other hand, preliminary catalytic experiments performed on the photo-oxidation of GSH and some amino acids such as l-methionine (Met), l-cysteine (Cys) and l-tryptophan (Trp) provide evidence for the photocatalytic activity of the Ir(III) complex in this type of reactions.“la Caixa” Banking Foundation (LCF/PR/PR12/11070003), Ministerio de Ciencia, Innovación y Universidades (RTI2018-102040-B-100 and RTI2018-100709-B-C21), Junta de Castilla y León (BU305P18, FEDER Funds

Bibliografía especializada de traducción sobre interpretación: el Proyecto Hermēneus de publicaciones de traducción e interpretación de la Facultad de Traducción e Interpretación de Soria - Universidad de Valladolid (1999-2011)

Producción CientíficaFrom 1999 up to the present, the Faculty of Translation of Interpreting at the University of Valladolid, Spain, has published three closely related series on Translation and Interpreting, the so-called Proyecto Hermēneus (Hermēneus Project): Hermēneus Journal, the Vertere Monographs, and Disbabelia, a collection of unknown translations. This paper seeks to make some of their features known as well as offer their full bibliographical data.La Facultad de Traducción e Interpretación de Soria, perteneciente a la Universidad de Valladolid, publica desde el año 1999 hasta la fecha tres series relacionadas entre sí dedicadas a la traducción y la interpretación, el llamado Proyecto Hermēneus compuesto por la revista Hermēneus, los monográficos Vertere y las traducciones ignotas Disbabelia. El presente trabajo comentará algunos rasgos de dichas colecciones, y recogerá los datos bibliográficos completos de las mismas

Role of Seroalbumin in the Cytotoxicity of cis-Dichloro Pt(II) Complexes with (N^N)-Donor Ligands Bearing Functionalized Tails

Given the potent anticancer properties of cisdiamminedichloroplatinum( II) and knowing its mode of action, we synthesized four new cis-[PtCl2(N^N)] organoplatinum complexes, two with N-substituted pbi ligands (pbiR = 1-R-2-(2-pyridyl)benzimidazole) (namely, 1 and 2) and two more with 4,4′-disubstituted bpy ligands (bpy = 2,2′-bipyridine) (namely, 3 and 4). We explored their cytotoxicity and ability to bind to deoxyguanosine monophosphate (dGMP), DNA, and albumin models. By 1H NMR and UV−vis spectroscopies, circular dichroism, agarose gel electrophoresis, differential scanning calorimetry measurements, and density functional theory calculations, we verified that only 3 can form aquacomplex species after dimethyl sulfoxide solvation; surprisingly, 1, 2, and 3 can bind covalently to DNA, whereas 4 can form a noncovalent complex. Interestingly, only complexes 1 and 4 exhibit good cytotoxicity against human ovarian carcinoma (HeLa) cell line, whereas 2 and 3 are inactive. Although lung carcinoma (A549) cells are more resistant to the four platinum complexes than HeLa cells, when the protein concentration in the extracellular media is lower, the cytotoxicity becomes substantially enhanced. By native electrophoresis of bovine seroalbumin (BSA) and inductively coupled plasma mass spectrometry uptake studies we bear out, on one hand, that 2 and 3 can interact strongly with BSA and its cellular uptake is negligible and, on the other hand, that 1 and 4 can interact with BSA only weakly, its cellular uptake being higher by several orders. These results point up the important role of the protein binding features on their biological activity and cellular uptake of cis-“PtCl2” derivatives. Our results are valuable in the future rational design of new platinum complexes with improved biological properties, as they expose the importance not only of their DNA binding abilities but also of additional factors such as protein binding.La Caixa Foundation (LCF/PR/PR12/11070003), Ministerio de Economía y Competitividad-FEDER (CTQ2014-58812-C2-2- R, CTQ2014-58812-C2-1-R, and CTQ2015-70371-REDT), Consejería de Educación−Junta de Castilla y León-FEDER (BU042U16), Spain

Alcian blue pyridine variant interaction with DNA and RNA polynucleotides and G-quadruplexes: changes in the binding features for different biosubstrates

This work concerns an analysis of the binding mechanism of a copper phthalocyanine (Alcian Blue-tetrakis(methylpyridinium) chloride, ABTP) to natural calf thymus DNA, G-quadruplexes (G4) and synthetic RNA polynucleotides in the form of double polyriboadenylic·polyribouridylic acid (poly(A)·poly(U)) or triple strands polyriboadenylic·2polyribouridylic acid (poly(A)·2poly(U)). ABTP is a well know dye that might undergo novel applications, but its interaction with DNA is scarcely studied and we lack information on possible RNA or G4 binding. This might be related to system complexity due to the presence of supramolecular dye-dye aggregates. Despite this, we show here that apparent parameters can be calculated, which provide information on the binding mechanism. Absorbance titrations in the presence of biosubstrate excess, melting and circular dichroism experiments show that ABTP binds to both RNAs and DNA. External/groove binding is the main feature for RNAs, whereas partial intercalation is the major binging mode for DNA. ABTP externally binds to both hybrid, parallel and anti-parallel G4s but seem to show a slightly different binding mode and a preference for anti-parallel structures. The thermodynamic features of the different systems are also discussed in the frame of the enthalpy-entropy compensation phenomenon.la Caixa” Foundation (LCF/PR/PR12/11070003), Ministerio de Ciencia, Innovación y Universidades-FEDER (RTI2018- 102040-B-100) and Junta de Castilla y León-FEDER (BU305P18

Combined spectroscopic and theoretical analysis of the binding of a water-soluble perylene diimide to DNA/RNA polynucleotides and G-quadruplexes

We present here a combined spectroscopic and theoretical analysis of the binding of N,N’-bis(2-(1-piperazino)ethyl)-3,4,9,10-perylenetetracarboxylic acid diimide dichloride (PZPERY) to different biosubstrates. Absorbance titrations and circular dichroism experiments, melting studies and isothermal calorimetry (ITC) titrations reveal a picture where the binding to natural double-stranded DNA is very different from that to double and triple-stranded RNAs (poly(A)∙poly(U) and poly(U)∙poly(A)⁎poly(U)). As confirmed also by the structural and energetic details clarified by density functional theory (DFT) calculations, intercalation occurs for DNA, with a process driven by the combination of aggregates disruption and monomers intercalation. Oppositely, for RNAs, no intercalation but groove binding with the formation of supramolecular aggregates is observed. Among all the tested biosubstrates, the affinity of PZPERY towards DNA G-quadruplexes (G4) is the greatest one with a preference for human telomeric G4s. Focusing on hybrid G4 forms, either sitting-atop (“tetrad-parallel”) or lateral (“groove-parallel”) binding modes were considered in the discussion of the experimental results and molecular dynamics (MD) simulations. Both turned out to be possible concurrently, in agreement also with the experimental binding stoichiometries higher than 2:1.“la Caixa” Foundation (LCF/PR/PR12/11070003), Ministerio de Ciencia, Innovación y Universidades-FEDER (RTI2018-102040-B-100) and Junta de Castilla y León-FEDER (BU305P18). LC acknowledges funding by the European Research Council, under the grant ERC-AdG-786714 (LIFETimeS

Sociedad naturaleza y turismo

Naturaleza y turismo parecen el pasado, pero todo es relativo ya que la naturaleza como tal no se aplica directamente en el turismo, este la transforma, la hace más amable y menos riesgosa, por ello hay quienes han planteado lo opuesto: diseñarla desde el inicio para crear un producto turístico a la medida. Sociedad naturaleza y turismo contienen una colección de ensayos presentados en el IV Seminario Internacional Nuevas Alternativas del Turismo, por un grupo de expertos en las ciencias sociales que plantean un conjunto de ideas sobre la creación y transformación de producto turístico

Graphic narratives for rethinking the world: comics-oriented projects for an inverted classroom and collaborative learning

Proyecto consistente en la creación de un club de lectura de cómics de temáticas enmarcadas en la Agenda 2030 autogestionado por estudiantes de grado, máster y doctorado, y egresados, y la ejecución de talleres llevados a cabo por profesorado y estudiantes tanto en la Facultad de Filología como en facultades de Educación, además de encuentros con autores y posts en redes sociales.Oficina para la CalidadDepto. de Estudios Ingleses: Lingüística y LiteraturaDepto. de Estudios Románicos, Franceses, Italianos y TraducciónFac. de FilologíaFac. de EducaciónFac. de Ciencias de la InformaciónFALSEsubmitte