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Cationic ionene as an n-dopant agent of poly(3,4-ethylenedioxythiophene)

Saborio, M. C.; Bertran, O.; Lanzalaco, S.; Häring, M.; Díaz, D. D.; Estrany, Francesc; Aleman, C.

Phys. Chem. Chem. Phys. 2018

We report the reduction of poly(3,4-ethylenedioxythiophene) (PEDOT) films with a cationic 1,4-diazabicyclo[2.2.2]octane-based ionene bearing N,N'-(meta-phenylene)dibenzamide linkages (mPI). Our main goal is to obtain n-doped PEDOT using a polymeric dopant agent rather than small conventional tetramethylammonium (TMA), as is usual. This has been achieved using a three-step process, which has been individually optimized: (1) preparation of p-doped (oxidized) PEDOT at a constant potential of +1.40 V in acetonitrile with LiClO4 as the electrolyte; (2) dedoping of oxidized PEDOT using a fixed potential of -1.30 V in water; and (3) redoping of dedoped PEDOT applying a reduction potential of -1.10 V in water with mPI. The resulting films display the globular appearance typically observed for PEDOT, with mPI being structured in separated phases forming nanospheres or ultrathin sheets. This organization, which has been supported by atomistic molecular dynamics simulations, resembles the nanosegregated phase distribution observed for PEDOT p-doped with poly(styrenesulfonate). Furthermore, the doping level achieved using mPI as the doping agent is comparable to that achieved using TMA, even though ionene provides distinctive properties to the conducting polymer. For example, films redoped with mPI exhibit much more hydrophilicity than the oxidized ones, whereas films redoped with TMA are hydrophobic. Similarly, films redoped with mPI exhibit the highest thermal stability, while those redoped with TMA show thermal stability that is intermediate between those of the latter and the dedoped PEDOT. Overall, the incorporation of an mPI polycation as the n-dopant into PEDOT has important advantages for modulating the properties of this emblematic conducting polymer.


Formaldehyde scavengers for cleaner production: A case study focused on the leather industry

Marsal, A., Cuadros, S., Ollé, L., Bacardit, A., Manich, A.M., Font, J.

Journal of Cleaner Production, 186, pp. 45-56. 2018

 Due to its carcinogenic character, the presence of formaldehyde in leather continues to be a subject of great concern. By using formaldehyde scavengers, it is possible to reduce the formaldehyde content in leather. In this work, the potential ability of three different compounds (ethylene urea, pyrogallol and gallic acid) to reduce the formaldehyde content in splits leathers treated with formaldehyde resins (melamine-formaldehyde and dicyandiamide-formaldehyde) is assessed. This capacity is compared with that of a fourth scavenger (hydroxylamine sulphate) already used in tanneries. The evolution of the formaldehyde content with time is also considered, as well as the potential coadjuvant effect of other compounds such as mimosa extract and an acid dye (Acid Black 234). Hydroxylamine sulphate initially showed the highest ability to reduce formaldehyde content. However, after a certain time, this ability proved to be inferior to the ability of other compounds due to the reversibility of the reaction between hydroxylamine and formaldehyde. Pyrogallol showed a higher ability than gallic acid when used in the final wash of leather processing. However, the treatment with pyrogallol results in a darkening of the leather; this darkening limits its use. Gallic acid may be a good alternative to formic acid as the final fixing agent in leather processing when the presence of formaldehyde in leathers is suspected. The use of gallic acid in the final wash or as a fixing agent fulfils the formaldehyde content limit (65–75?mg/kg) of the major brands in leather goods in direct contact with the skin. The addition of 2% of gallic acid in the final wash of leather processing resulted in formaldehyde content reductions that varied from 65% to 85%. However, further experiments are required to assess the influence of gallic acid on the fastness properties and the coloration acquired by the treated leathers. The joint effect of gallic acid in the final wash or as a fixing agent and mimosa extract as a retanning agent in formaldehyde content reduction is even enhanced by subsequently using a dye with amino groups in its chemical structure. Reducing the formaldehyde content by using scavengers can contribute to the achievement of a cleaner production in those sectors (leather, textile, wood) that use formaldehyde resins.


Glucose-nucleobase pairs within DNA: Impact of hydrophobicity, alternative linking unit and DNA polymerase nucleotide insertion studies

Vengut-Climent, E., Peñalver, P., Lucas, R., Gómez-Pinto, I., Aviñó, A., Muro-Pastor, A.M., Galbis, E., De Paz, M.V., Fonseca Guerra, C., Bickelhaupt, F.M., Eritja, R., González, C., Morales, J.C.

Chemical Science, 9 (14), pp. 3544-3554. 2018

Recently, we studied glucose-nucleobase pairs, a binding motif found in aminoglycoside–RNA recognition. DNA duplexes with glucose as a nucleobase were able to hybridize and were selective for purines. They were less stable than natural DNA but still fit well on regular B-DNA. These results opened up the possible use of glucose as a non-aromatic DNA base mimic. Here, we have studied the incorporation and thermal stability of glucose with different types of anchoring units and alternative apolar sugar-nucleobase pairs. When we explored butanetriol instead of glycerol as a wider anchoring unit, we did not gain duplex thermal stability. This result confirmed the necessity of a more conformationally restricted linker to increase the overall duplex stability. Permethylated glucose-nucleobase pairs showed similar stability to glucoside-nucleobase pairs but no selectivity for a specific nucleobase, possibly due to the absence of hydrogen bonds between them. The three-dimensional structure of the duplex solved by NMR located both, the hydrophobic permethylated glucose and the nucleobase, inside the DNA helix as in the case of glucose-nucleobase pairs. Quantum chemical calculations on glucose-nucleobase pairs indicate that the attachment of the sugar to the DNA skeleton through the OH1 or OH4 positions yields the highest binding energies. Moreover, glucose was very selective for guanine when attached through OH1 or OH4 to the DNA. Finally, we examined DNA polymerase insertion of nucleotides in front of the saccharide unit. KF- polymerase from E. coli inserted A and G opposite glc and 6dglc with low efficiency but notable selectivity. It is even capable of extending the new pair although its efficiency depended on the DNA sequence. In contrast, Bst 2.0, SIII and BIOTAQ™ DNA polymerases seem to display a loop-out mechanism possibly due to the flexible glycerol linker used instead of deoxyribose.


Influence of process variables in a continuous treatment of non-sterile hospital wastewater by Trametes versicolor and novel method for inoculum production

Mir-Tutusaus, J.A., Caminal, G., Sarrà, M.

 Journal of Environmental Management, 212, pp. 415-423, 2018

 Micropollutants such as pharmaceutical active compounds, present at high concentration in hospital wastewater (HWW), pose both environmental and human health challenges. Fungal reactors can effectively remove such contaminants and produce non-toxic effluents, but their ability to operate for a long period of time is yet to be demonstrated in real hospital wastewater. Several process variables need to be studied beforehand. Here, variables: pellet size, aeration and carbon-to-nitrogen ratio are studied in continuous operations with real HWW. Moreover, a novel strategy for inoculum production that could reduce economical and operational costs is proposed and tested. Optimum pellet size was found to be 2?mm and an aeration of 0.8?L?min-1 was needed to maintain fungal viability. The carbon-to-nitrogen ratio of 7.5 was selected and the pellet production time was reduced from 6 to 3 days. The novel low-cost inoculum preparation produced pellets with the same characteristics as the traditionally prepared ones.


Shedding light on metabotropic glutamate receptors using optogenetics and photopharmacology

Goudet, C., Rovira, X., Llebaria, A.

 Current Opinion in Pharmacology, 38, pp. 8-15, 2018

 Metabotropic glutamate receptors (mGluRs) are a family of G protein-coupled receptors activated by glutamate, the main excitatory neurotransmitter of the mammalian central nervous system. These receptors are considered as potential therapeutic targets in many neurological diseases but a better understanding of their complex molecular dynamics and of their role in the normal and pathological functioning of the brain is still required. Manipulating mGluRs with high spatial and temporal precision holds great promise for deciphering their physiological and pathological functions. This article reviews several recently developed optogenetic and photopharmacological solutions for the optical control of mGluRs and their applications, from the study of the molecular dynamics of receptor activation to the study of their roles in vivo.


Isosteric Substitution of 4H-1,2,4-Triazole by 1H-1,2,3-Triazole in Isophthalic Derivative Enabled Hydrogel Formation for Controlled Drug Delivery

Häring, M.; Rodríguez-López, J.; Grijalvo, S.; Tautz, M.; Eritja, R.; Martín, V. S.; Díaz, D. D.

Mol. Pharm. 2018

 In this work, we demonstrated that the simple substitution of the 1,2,4-triazole moiety in 5-(4H-1,2,4-triazol-4-yl)isophthalic acid (5-TIA) by the 1H-1,2,3-triazol-5-yl unit enables the preparation of a hydrogelator (click-TIA). In sharp contrast to 5-TIA, its isostere click-TIA undergoes self-assembly in water upon sonication, leading to the formation of stable supramolecular viscoelastic hydrogels with a critical gelation concentration of 6 g/L. Hydrogels made of click-TIA as well as hybrid hydrogels made of the mixture click-TIA + 5-TIA (molar ratio 1:0.2) were used to compare different properties of the materials (i.e., rheological properties, thermal properties, mechanical stability, morphology). In terms of toxicity, neither click-TIA nor 5-TIA showed cytotoxic effects on cellular viability of HeLa cells up to 2.3 × 10–3 g/L when compared to untreated cells incubated with DMSO. Furthermore, the hydrogels were used for the encapsulation and in vitro controlled release of oxytetracycline that followed first-order kinetics. For the hydrogel made of click-TIA, a maximum drug release of ~60% was reached after ~8 h within a pH range between 6.5 and 10. However, the release rate was reduced to approximately half of its value at pH values between 1.2 and 5.0, whereas the use of hybrid hydrogels made of click-TIA + 5-TIA allowed to reduce the original rate at pH = 6.5.


SOD3 improves the tumor response to chemotherapy by stabilizing endothelial HIF-2a

Emilia Mira, Lorena Carmona-Rodríguez, Beatriz Pérez-Villamil, Josefina Casas,María Jesús Fernández-Aceñero, Diego Martínez-Rey, Paula Martín-González, Ignacio Heras-Murillo, Mateo Paz-Cabezas, Manuel Tardáguila, Tim D. Oury, Silvia Martín-Puig, Rosa Ana Lacalle, Gemma Fabriás, Eduardo Díaz-Rubio and Santos Mañes


 One drawback of chemotherapy is poor drug delivery to tumor cells, due in part to hyperpermeability of the tumor vasculature. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme usually repressed in the tumor milieu. Here we show that specific SOD3 re-expression in tumor-associated endothelial cells (ECs) increases doxorubicin (Doxo) delivery into and chemotherapeutic effect on tumors. Enhanced SOD3 activity fostered perivascular nitric oxide accumulation and reduced vessel leakage by inducing vascular endothelial cadherin (VEC) transcription. SOD3 reduced HIF prolyl hydroxylase domain protein activity, which increased hypoxia-inducible factor-2a (HIF-2a) stability and enhanced its binding to a specific VEC promoter region. EC-specific HIF-2a ablation prevented both the SOD3-mediated increase in VEC transcription and the enhanced Doxo effect. SOD3, VEC, and HIF-2a levels correlated positively in primary colorectal cancers, which suggests a similar interconnection of these proteins in human malignancy.


Wet-Chemical Etching of GaN: Underlying Mechanism of a Key Step in Blue and White LED Production

Tautz, M.; Díaz, D. D.

 ChemistrySelect 2018


 Gallium nitride (GaN) is the key material for the fabrication of blue and white light emitting diodes (LEDs). Etching of this material is applied to improve the light extraction efficiency of the product. Wet-chemical etching of GaN is commonly carried out by treatment with aqueous KOH solution at elevated temperature. Thereby, the anisotropic etching results in a highly rough surface. Hence, a remarkably higher out-coupling possibility of generated photons is feasible. On the other hand, anisotropy generally prohibits the application of a predictable and standardized etching process. In this review, both material- and process-dependent influences on the etching performance in aqueous KOH solution are classified. Herein, we critically present the factors that affect the etching rate of GaN. Moreover, the etching mechanism at the molecular level and the generation of anisotropy from the hexagonal crystal lattice are discussed. The existing gaps in the current understanding of this process maintain the field still open for further research aligned to a permanent interest of the electronic industry.


Dihydroceramide Desaturase 1 Inhibitors Reduce Amyloid-â Levels in Primary Neurons from an

Ordóñez-Gutiérrez, L., Benito-Cuesta, I., Abad, J.L., Casas, J., Fábrias, G., Wandosell, F.

Pharmaceutical Research, 35 (3), art. no. 49,

Purpose: The induction of autophagy has recently been explored as a promising therapeutic strategy to combat Alzheimer’s disease. Among many other factors, there is evidence that ceramides/dihydroceramides act as mediators of autophagy, although the exact mechanisms underlying such effects are poorly understood. Here, we describe how two dihydroceramide desaturase inhibitors (XM461 and XM462) trigger autophagy and reduce amyloid secretion by neurons. Methods: Neurons isolated from wild-type and APP/PS1 transgenic mice were exposed to the two dihydroceramide desaturase inhibitors to assess their effect on these cell’s protein and lipid profiles. Results: Both dihydroceramide desaturase inhibitors increased the autophagic vesicles in wild-type neurons, reflected as an increase in LC3-II, and this was correlated with the accumulation of dihydroceramides and dihydrosphingomyelins. Exposing APP/PS1 transgenic neurons to these inhibitors also produced a 50% reduction in amyloid secretion and/or production. The lipidomic defects triggered by these dihydroceramide desaturase inhibitors were correlated with a loss of S6K activity, witnessed by the changes in S6 phosphorylation, which strongly suggested a reduction of mTORC1 activity. Conclusions: The data obtained strongly suggest that dihydroceramide desaturase 1 activity may modulate autophagy and mTORC1 activity in neurons, inhibiting amyloid secretion and S6K activity. As such, it is tantalizing to propose that dihydroceramide desaturase 1 may be an important therapeutic target to combat amyloidosis.


Evaluation of the effect of polymorphism on G-quadruplex-ligand interaction by means of spectroscopic and chromatographic techniques

Benito, S., Ferrer, A., Benabou, S., Aviñó, A., Eritja, R., Gargallo, R.

 Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 196, 185-195, 2018

 Guanine-rich sequences may fold into highly ordered structures known as G-quadruplexes. Apart from the monomeric G-quadruplex, these sequences may form multimeric structures that are not usually considered when studying interaction with ligands. This work studies the interaction of a ligand, crystal violet, with three guanine-rich DNA sequences with the capacity to form multimeric structures. These sequences correspond to short stretches found near the promoter regions of c-kit and SMARCA4 genes. Instrumental techniques (circular dichroism, molecular fluorescence, size-exclusion chromatography and electrospray ionization mass spectrometry) and multivariate data analysis were used for this purpose. The polymorphism of G-quadruplexes was characterized prior to the interaction studies. The ligand was shown to interact preferentially with the monomeric G-quadruplex; the binding stoichiometry was 1:1 and the binding constant was in the order of 105 M−1 for all three sequences. The results highlight the importance of DNA treatment prior to interaction studies.


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