H(N3)dap (Hdap = 2,6-Diaminopurine) Recognition by Cu2(EGTA): Structure, Physical Properties, and Density Functional Theory Calculations of [Cu4( -EGTA)2( -H(N3)dap)2(H2O)2] 7H2O

Reactions inwater between the Cu2( -EGTA) chelate (EGTA= ethylene-bis(oxyethyleneimino) tetraacetate(4-) ion) and Hdap in molar ratios 1:1 and 1:2 yield only blue crystals of the ternary compound [Cu4( -EGTA)2( -H(N3)dap)2(H2O)2] 7H2O (1), which has been studied via single-crystal X-ray diffraction and various physical methods (thermal stability, spectral and magnetic properties), as well as DFT theoretical calculations. In the crystal, uncoordinated water is disordered. The tetranuclear complex molecule also has some irrelevant disorder in an EGTA-ethylene moiety. In the complex molecule, both bridging organic molecules act as binucleating ligands. There are two distorted five- and two six-coordinated Cu(II) centers. Each half of EGTA acts as a tripodal tetradentate Cu(II) chelator, with a mer-NO2 + O(ether, distal) conformation. Hdap exhibits the tautomer H(N3)dap, with the dissociable H-atom on its less basic N-heterocyclic atom. These features favor the efficient cooperation between Cu-N7 or Cu-N9 bonds with appropriate O-EGTA atoms, as N6-H O or N3-H O interligand interactions, respectively. The bridging role of both organics determines the tetranuclear dimensionality of the complex. In this crystal, such molecules associate in zig-zag chains built by alternating – interactions between the five- or six-atom rings of Hdap ligands of adjacent molecules. DFT theoretical calculations (using two different theoretical models and characterized by the quantum theory of “atoms in molecules”) reveal the importance of these – interactions between Hdap ligands, as well as those corresponding to the referred hydrogen bonds in the contributed tetranuclear moleculeMICIU/AEI of Spain project PID2020-115637GB-I00 FEDER, MICINN of Spain project PGC2018-102047-B-I00Project B-FQM-478-UGR20 (FEDER-Universidad de Granada, Spain)FQM-283 (Junta de Andalucía, Spain

Novel Cd (II) Coordination Polymers Afforded with EDTA or Trans-1,2-Cdta Chelators and Imidazole, Adenine, or 9-(2-Hydroxyethyl) Adenine Coligands

We thank the “Centre de Tecnologies de la Informació” (CTI), Universitat de les Illes Balears for computational facilities. We also thank all Projects for financial support.Three mixed-ligands of Cd(II) coordination polymers were unintentionally obtained: {[Cd(µ3-EDTA)(Him)·Cd(Him)(H2O)2]·H2O}n (1), {[Cd(µ4-CDTA)(Hade)·Cd(Hade)2]}n (2), and {[Cd(µ3-EDTA)(H2O)·Cd(H9heade)(H2O)]·2H2O}n (3), having imidazole (Him), adenine (Hade) or 9-(2-hydroxyethyl)adenine (9heade) as the N-heterocyclic coligands. Compounds 2 and 3 were obtained by working with an excess of corresponding N-heterocyclic coligands. The single-crystal X-ray diffraction structures and thermogravimetric analyses are reported. The chelate moieties in all three compounds exhibit hepta-coordinated Cd centers, whereas the non-chelated Cd center is five-coordinated in 1 and six-coordinated in 2 and 3. Him and Hade take part in the seven-coordinated chelate moieties in 1 and 2, respectively. In contrast, 9heade is unable to replace the aqua ligand of the chelate [Cd (EDTA) (H2O)] moiety in 3. The thermogravimetric analysis (TGA) behavior of [Cd (H2EDTA) (H2O)]·2H2O in 1 and 3 leads to a residue of CdO, whereas the N-rich compound 2 yields CdO·Cd(NO3)2 as a residue. Density functional theory (DFT) calculations along with molecular electrostatic potential (MEP) and quantum theory of atoms-in-molecules computations were performed in adenine (compound 2) and (2-hydroxyethyl)adenine (compound 3) to analyze how the strength of the H-bonding and π-stacking interactions, respectively, are affected by their coordination to the Cd-metal center.Excellence Network "Metal Ions in Biological Systems" MetalBio CTQ2017-90802-REDTJunta de Andalucia FQM-283MICIU /AEI of Spain CTQ2017-85821-

You must be the change you want to see in the University

Se discutirán las dos primeras misiones de la Universidad, tales como la docencia y la investigación. Además, las relaciones inter-personales son fundamentales en todo grupo humano y se abordará el papel del liderazgo en el grupo de investigación de acuerdo con las modernas tendencias del mundo empresarial. La Universidad española se encuentra en una situación excesivamente alejada de la realidad social y económica en la que vivimos. El enfoque del Espacio Europeo de Enseñanza Superior puede subsanar estas deficiencias, pero la adaptación conlleva, en mayor o menor grado, una transformación del modelo educativo actual. Lo que no está claro es que las universidades españolas hayan alcanzado o estén en vías de alcanzar plenamente la nueva configuración de la Declaración de Bolonia. Más bien están en una situación transitoria, ambigua, en la que permanecen rasgos anteriores con los nuevos. Con respecto al papel carismático del líder dentro de un grupo, merecen ser destacados aspectos tales como la motivación, delegación y resolución de conflictos, entre los muchos valores que deben adornarlo. La Universidad de Granada es una institución muy grande. El secreto para que funcione esta macro estructura es que cada uno de sus componentes, dentro de su status, se identifique con sus principios y se comprometa a cumplir con sus funciones, tanto particulares como generales. El secreto del éxito es la ilusión, trabajo y generosidad. Es así y sólo así, cuando el trabajo y la colaboración comprometida de todos sus miembros, dará lugar a una Universidad mejor.Teaching and research, two missions of the University, will be discussed herein. Moreover, the interpersonal relationships are fundamental in all human groups and the role of the leadership in the research group will be tackled according to the modern tendencies of the business world. The Spanish University has been too distanced from the social and economical reality. The approach of the European higher education system may overcome all these shortcomings, but the adaptation may lead, to a greater or a lesser degree, to a transformation of the present education system. It is not clear that the Spanish universities have reached or are now being fully reaching the new configuration of the Bologna Declaration. They are rather in a temporary ambiguous situation, in which some previous features remain with the new ones. In relation to the charismatic role of the leader within a group, aspects such as motivation, delegation of functions and resolution of conflicts warrant the greatest attention among the many values that must enhance it. The University of Granada is a vast institution. The secret for this macro-structure to work is that its components, each within its own status, be identified with its principles and be committed to observing its functions, both particular and general. The secret of the success is illusion, work and generosity. Only thus, when work and collaboration implicating all its members is a better University possible

Covalent Immobilization of Antibodies through Tetrazine-TCO Reaction to Improve Sensitivity of ELISA Technique

This research was funded by Compra Publica Precomercial, Reference 2012/000069, Ministerio de Economia y Competitividad, Espana. ONCOVER project: Volatile compound detection system for early cancer diagnosis.Enzyme-linked immunosorbent assay (ELISA) is routinely used to detect biomolecules related to several diseases facilitating diagnosis and monitoring of these, as well as the possibility of decreasing their mortality rate. Several methods have been carried out to improve the ELISA sensitivity through antibodies immobilization on the microtiter plates. Here, we have developed a strategy of antibodies immobilization to improve the ELISA sensitivity increasing the antibody density surface through the tetrazine (Tz)-trans-cyclooctene (TCO) reaction. For this, we prepared surfaces with tetrazine groups while the captured antibody was conjugated with TCO. The tetrazine surfaces were prepared in two different ways: (1) from aminated plates and (2) from Tz-BSA-coated plates. The surfaces were evaluated using two sandwich ELISA models, one of them using the low-affinity antibody anti-c-myc as a capture antibody to detect the c-myc-GST-IL8h recombinant protein, and the other one to detect the carcinoembryonic human protein (CEA). The sensitivity increased in both surfaces treated with tetrazine in comparison with the standard unmodified surface. The c-myc-GST-IL8h detection was around 10-fold more sensible on both tetrazine surfaces, while CEA ELISA detection increased 12-fold on surfaces coated with Tz-BSA. In conclusion, we show that it is possible to improve the ELISA sensitivity using this immobilization system, where capture antibodies bond covalently to surfaces.Compra Publica Precomercial, Ministerio de Economia y Competitividad, Espana 2012/00006

Novel Cd (II) Coordination Polymers Afforded with EDTA or Trans-1,2-Cdta Chelators and Imidazole, Adenine, or 9-(2-Hydroxyethyl) Adenine Coligands

Three mixed-ligands of Cd(II) coordination polymers were unintentionally obtained: {[Cd(µ3-EDTA)(Him)·Cd(Him)(H2O)2]·H2O}n (1), {[Cd(µ4-CDTA)(Hade)·Cd(Hade)2]}n (2), and {[Cd(µ3-EDTA)(H2O)·Cd(H9heade)(H2O)]·2H2O}n (3), having imidazole (Him), adenine (Hade) or 9-(2-hydroxyethyl)adenine (9heade) as the N-heterocyclic coligands. Compounds 2 and 3 were obtained by working with an excess of corresponding N-heterocyclic coligands. The single-crystal X-ray diffraction structures and thermogravimetric analyses are reported. The chelate moieties in all three compounds exhibit hepta-coordinated Cd centers, whereas the non-chelated Cd center is five-coordinated in 1 and six-coordinated in 2 and 3. Him and Hade take part in the seven-coordinated chelate moieties in 1 and 2, respectively. In contrast, 9heade is unable to replace the aqua ligand of the chelate [Cd (EDTA) (H2O)] moiety in 3. The thermogravimetric analysis (TGA) behavior of [Cd (H2EDTA) (H2O)]·2H2O in 1 and 3 leads to a residue of CdO, whereas the N-rich compound 2 yields CdO·Cd(NO3)2 as a residue. Density functional theory (DFT) calculations along with molecular electrostatic potential (MEP) and quantum theory of atoms-in-molecules computations were performed in adenine (compound 2) and (2-hydroxyethyl)adenine (compound 3) to analyze how the strength of the H-bonding and π-stacking interactions, respectively, are affected by their coordination to the Cd-metal centerThis research was funded by the Excellence Network “Metal Ions in Biological Systems” MetalBio CTQ2017-90802-REDT, the Research group FQM-283 (Junta de Andalucía), and MICIU/AEI of Spain (project CTQ2017-85821-R FEDER funds)S

Dicopper(II)-EDTA Chelate as a Bicephalic Receptor Model for a Synthetic Adenine Nucleoside

In the extensive field of metal ions, their interactions with nucleic acids, and their constituents, the main aim of this work is to develop a metal chelate suitable to recognize two molecules of an adenine nucleoside. For this purpose, the dinuclear chelate Cu2 (µ-EDTA) (ethylenediaminetetraacetate(4-) ion (EDTA)) is chosen as a bicephalic receptor model for N9-(2-hydroxyethyl)adenine (9heade). A one-pot synthesis is reported to obtain the compound [Cu2 (µ2 -EDTA)(9heade)2 (H2O)4 ]·3H2O, which has been characterized by single-crystal X-ray diffraction and various spectral, thermal, and magnetic methods. The complex unit is a centro-symmetric molecule, where each Cu (II) center is chelated by a half-EDTA, and is further surrounded by an N7-dentate 9heade nucleoside and two non-equivalent trans-O-aqua molecules. The metal chelate-nucleoside molecular recognition is referred to as an efficient cooperation between the Cu-N7(9heade) coordination bond and a (9heade)N6-H···O(carboxyl, EDTA) interligand interaction. Theoretical calculations are also made to account for the relevance of this interaction. The extreme weakness with which each water molecule binds to the metal center disturbs the thermal stability and the infrared (FT-IR) and electron spin resonance (ESR) spectra of the compound.Agencia Estatal de Investigación, Ministerio de Ciencia, Innovación y Universidades (MICIU) from SpainFEDER-EU (project nos. PGC2018-102047-B-I00 and CTQ2017-85821-R)Junta de Andalucía (research group FQM-283)University of Granada (project ref. PPJIA2019-03

Phenformin as an Anticancer Agent: Challenges and Prospects

Currently, there is increasing evidence linking diabetes mellitus (especially type 2 diabetes mellitus) with carcinogenesis through various biological processes, such as fat-induced chronic inflammation, hyperglycemia, hyperinsulinemia, and angiogenesis. Chemotherapeutic agents are used in the treatment of cancer, but in most cases, patients develop resistance. Phenformin, an oral biguanide drug used to treat type 2 diabetes mellitus, was removed from the market due to a high risk of fatal lactic acidosis. However, it has been shown that phenformin is, with other biguanides, an authentic tumor disruptor, not only by the production of hypoglycemia due to caloric restriction through AMP-activated protein kinase with energy detection (AMPK) but also as a blocker of the mTOR regulatory complex. Moreover, the addition of phenformin eliminates resistance to antiangiogenic tyrosine kinase inhibitors (TKI), which prevent the uncontrolled metabolism of glucose in tumor cells. In this review, we evidence the great potential of phenformin as an anticancer agent. We thoroughly review its mechanism of action and clinical trial assays, specially focusing on current challenges and future perspectives of this promising drug.This research was supported by the Fundación Mutua Madrileña (project FMM-AP16683-2017), Consejería de Salud Junta de Andalucía (PI-0089-2017), the MNat Scientitc Unit of Excellence (UCE.PP2017.0f) and the Chair “Doctors Galera-Requena in cancer stem cell research”

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: constraints on the time variation of fundamental constants from the large-scale two-point correlation function

We obtain constraints on the variation of the fundamental constants from the full shape of the redshift-space correlation function of a sample of luminous galaxies drawn from the Data Release 9 of the Baryonic Oscillations Spectroscopic Survey. We combine this information with data from recent CMB, BAO and H_0 measurements. We focus on possible variations of the fine structure constant \alpha and the electron mass m_e in the early universe, and study the degeneracies between these constants and other cosmological parameters, such as the dark energy equation of state parameter w_DE, the massive neutrinos fraction f_\nu, the effective number of relativistic species N_eff, and the primordial helium abundance Y_He. When only one of the fundamental constants is varied, our final bounds are \alpha / \alpha_0 = 0.9957_{-0.0042}^{+0.0041} and m_e /(m_e)_0 = 1.006_{-0.013}^{+0.014}. For their joint variation, our results are \alpha / \alpha_0 = 0.9901_{-0.0054}^{+0.0055} and m_e /(m_e)_0 = 1.028 +/- 0.019. Although when m_e is allowed to vary our constraints on w_DE are consistent with a cosmological constant, when \alpha is treated as a free parameter we find w_DE = -1.20 +/- 0.13; more than 1 \sigma away from its standard value. When f_\nu and \alpha are allowed to vary simultaneously, we find f_\nu < 0.043 (95% CL), implying a limit of \sum m_\nu < 0.46 eV (95% CL), while for m_e variation, we obtain f_nu < 0.086 (95% CL), which implies \sum m_\nu < 1.1 eV (95% CL). When N_eff or Y_He are considered as free parameters, their simultaneous variation with \alpha provides constraints close to their standard values (when the H_0 prior is not included in the analysis), while when m_e is allowed to vary, their preferred values are significantly higher. In all cases, our results are consistent with no variations of \alpha or m_e at the 1 or 2 \sigma level.Comment: 18 pages, 16 figures. Submitted to MNRA

CMB polarization as a probe of the anomalous nature of the Cold Spot

One of the most interesting explanations for the non-Gaussian Cold Spot (CS) detected in the WMAP data by Vielva et al. 2004, is that it arises from the interaction of the CMB radiation with a cosmic texture (Cruz et al. 2007b). In this case, a lack of polarization is expected in the region of the spot, as compared to the typical values associated to large fluctuations of a GIRF. In addition, other physical processes related to a non-linear evolution of the gravitational field could lead to a similar scenario. However, some of these alternative scenarios (e.g., a large void in the large scale structure) have been shown to be very unlikely. In this work we characterise the polarization properties of the Cold Spot under both hypotheses: a large Gaussian spot and an anomalous feature generated, for instance, by a cosmic texture. We propose a methodology to distinguish between them, and we discuss its discrimination power as a function of the instrumental noise level. In particular, we address the cases of current experiments, like WMAP and Planck, and others in development as QUIJOTE. We find that for an ideal experiment the Gaussian hypothesis could be rejected at a significance level better than 0.8%. While WMAP is far from providing useful information in this respect, we find that Planck will be able to reach a significance of around 7%; in addition, we show that the ground-based experiment QUIJOTE could provide a significance of around 1%. If these results are combined with the significance level found for the CS in temperature, the capability of QUIJOTE and Planck to reject the alternative hypothesis becomes 0.025% and 0.124%, respectively.Comment: 7 pages, 3 figures, accepted in MNRAS. Minor changes made to match the final versio