Desarrollo de recursos docentes para la evaluación de competencias transversales en los Grados de la Facultad de Ciencias de la UBU

Ponencia presentada en: VIII Jornadas de Innovación Docente de la UBU, Burgos, 5 de abril de 2016, organizadas por el Instituto de Formación e Innovación Educativa-IFIE de la Universidad de Burgo

Photocatalytic Aerobic Dehydrogenation of N-Heterocycles with Ir(III) Photosensitizers Bearing the 2(2′-Pyridyl)benzimidazole Scaffold

Photoredox catalysis constitutes a very powerful tool in organic synthesis, due to its versatility, efficiency, and the mild conditions required by photoinduced transformations. In this paper, we present an efficient and selective photocatalytic procedure for the aerobic oxidative dehydrogenation of partially saturated N-heterocycles to afford the respective N-heteroarenes (indoles, quinolines, acridines, and quinoxalines). The protocol involves the use of new Ir(III) biscyclometalated photocatalysts of the general formula [Ir(C^N)2(N^N′)]Cl, where the C^N ligand is 2- (2,4-difluorophenyl)pyridinate, and N^N′ are different ligands based on the 2-(2′-pyridyl)benzimidazole scaffold. In-depth electrochemical and photophysical studies as well as DFT calculations have allowed us to establish structure−activity relationships, which provide insights for the rational design of efficient metal-based dyes in photocatalytic oxidation reactions. In addition, we have formulated a dual mechanism, mediated by the radical anion superoxide, for the above-mentioned transformations.We acknowledge the financial support provided by the Spanish Ministerio de Ciencia, Innovación y Universidades (RTI2018- 100709-B-C21 and CTQ (QMC)-RED2018-102471-T), Consejería de Educación de la Junta de Castilla y León and FEDER (BU087G19 and BU067P20), and Junta de Comunidades de Castilla-La Mancha-FEDER (JCCM) (grant SBPLY/19/ 180501/000260). I.E. acknowledges his fellowship to both the European Social Fund and Consejería de Educación de la Junta de Castilla y León (EDU/1100/2017). We are also indebted to J. Delgado, P. Castroviejo, and M. Mansilla (PCT of the Universidad de Burgos) for technical support, G. GarcíaHerbosa for providing us access to CV equipment, and J. V. Cuevas-Vicario for support with Gaussian

Highly stable and efficient light-emitting electrochemical cells based on cationic iridium complexes bearing arylazole ancillary ligands

A series of bis-cyclometalated iridium(III) complexes of general formula [Ir(ppy)2(N∧N)][PF6] (ppy− = 2-phenylpyridinate; N∧N = 2-(1H-imidazol-2-yl)pyridine (1), 2-(2-pyridyl)benzimidazole (2), 1-methyl-2-pyridin-2-yl- 1H-benzimidazole (3), 2-(4′-thiazolyl)benzimidazole (4), 1- methyl-2-(4′-thiazolyl)benzimidazole (5)) is reported, and their use as electroluminescent materials in light-emitting electrochemical cell (LEC) devices is investigated. [2][PF6] and [3][PF6] are orange emitters with intense unstructured emission around 590 nm in acetonitrile solution. [1][PF6], [4][PF6], and [5][PF6] are green weak emitters with structured emission bands peaking around 500 nm. The different photophysical properties are due to the effect that the chemical structure of the ancillary ligand has on the nature of the emitting triplet state. Whereas the benzimidazole unit stabilizes the LUMO and gives rise to a 3MLCT/3LLCT emitting triplet in [2][PF6] and [3][PF6], the presence of the thiazolyl ring produces the opposite effect in [4][PF6] and [5][PF6] and the emitting state has a predominant 3LC character. Complexes with 3MLCT/3LLCT emitting triplets give rise to LEC devices with luminance values 1 order higher than those of complexes with 3LC emitting states. Protecting the imidazole N−H bond with a methyl group, as in complexes [3][PF6] and [5][PF6], shows that the emissive properties become more stable. [3][PF6] leads to outstanding LECs with simultaneously high luminance (904 cd m−2), efficiency (9.15 cd A−1), and stability (lifetime over 2500 h).Spanish Ministry of Economy and Competitiveness (MINECO) of Spain (projects CTQ2014- 58812-C2-1-R, MAT2014-55200, CTQ2014-55583-R, CTQ2014-61914-EXP, CTQ2015-71955-REDT, CTQ2015- 70371-REDT, CTQ2015-71154-P, and Unidad de Excelencia Marıá de Maeztu MDM-2015-0538), European Feder funds (CTQ2015-71154-P), Obra Social “la Caixa” (OSLC-2012- 007), Junta de Castilla y León (BU033-U16), and Generalitat Valenciana (Prometeo2016/135

Targets, Mechanisms and Cytotoxicity of Half-Sandwich Ir(III) Complexes Are Modulated by Structural Modifications on the Benzazole Ancillary Ligand

Cancers are driven by multiple genetic mutations but evolve to evade treatments targeting specific mutations. Nonetheless, cancers cannot evade a treatment that targets mitochondria, which are essential for tumor progression. Iridium complexes have shown anticancer properties, but they lack specificity for their intracellular targets, leading to undesirable side effects. Herein we present a systematic study on structure-activity relationships of eight arylbenzazole-based Iridium(III) complexes of type [IrCl(Cp*)], that have revealed the role of each atom of the ancillary ligand in the physical chemistry properties, cytotoxicity and mechanism of biological action. Neutral complexes, especially those bearing phenylbenzimidazole (HL1 and HL2), restrict the binding to DNA and albumin. One of them, complex 1[C,NH-Cl], is the most selective one, does not bind DNA, targets exclusively the mitochondria, disturbs the mitochondria membrane permeability inducing proton leak and increases ROS levels, triggering the molecular machinery of regulated cell death. In mice with orthotopic lung tumors, the administration of complex 1[C,NH-Cl] reduced the tumor burden. Cancers are more vulnerable than normal tissues to a treatment that harnesses mitochondrial dysfunction. Thus, complex 1[C,NH-Cl] characterization opens the way to the development of new compounds to exploit this vulnerabilityWe acknowledge the “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) for financial support. Networking support by COST Action CA18202 (NECTAR) is also acknowledged

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

Rational design of mitochondria targeted thiabendazole-based Ir(III) biscyclometalated complexes for a multimodal photodynamic therapy of cancer

Despite their outstanding properties as potential photosensitizers for photodynamic therapy (PDT), Ir(III) biscyclometalated complexes need both further developments to overcome remaining limitations and in-depth investigations into their mechanisms of action to reach clinic application in the treatment of cancer. This work describes the synthesis of a family of Ir(III) complexes of general formula [Ir(C^N)2(N^N′ )]Cl (N^N′ = thiabendazole-based ligands; C^N = ppy (2-phenylpyridinate) (Series A), or dfppy (2-(2,4-difluorophenyl)pyridinate) (Series B)) and their evaluation as potential PDT agents. These complexes are partially soluble in water and exhibit cytotoxic activity in the absence of light irradiation versus several cancer cell lines. Furthermore, the cytotoxic activity of derivatives of Series A is enhanced upon irradiation, particularly for complexes [1a]Cl and [3a]Cl, which show phototoxicity indexes (PI) above 20. Endocytosis was established as the uptake mechanism for [1a]Cl and [3a]Cl in prostate cancer cells by flow cytometry. These derivatives mainly accumulate in the mitochondria as shown by colocalization confocal microscopy experiments. Presumably, [1a]Cl and [3a]Cl induce death on cancer cells under irradiation through apoptosis triggered by a multimodal mechanism of action, which likely involves damage over mitochondrial DNA and mitochondrial membrane depolarization. Both processes seem to be the result of photocatalytic oxidation processes.We acknowledge the financial support provided by the Spanish Ministerio de Ciencia, Innovacion ´ y Universidades (RTI2018-100709-BC21, RTI2018-100709-B-C22) and CTQ (QMC)-RED2018-102471-T), Junta de Castilla y Leon ´ (BU087G19), Junta de Comunidades de CastillaLa Mancha-FEDER (JCCM) (grant SBPLY/19/180501/000260) and UCLM-FEDER (grants 2019-GRIN-27183 and 2019-GRIN-27209). I. Echevarría wants to acknowledge his fellowship to both the European Social Fund and Consejería de Educacion ´ de la Junta de Castilla y Leon ´ (EDU/1100/2017). E. Zafon wants to acknowledge her predoctoral fellowship to the Generalitat de Catalunya (AGAUR; 2021 FI_B 01036). We are also indebted to Jacinto Delgado, Pilar Castroviejo and Marta Mansilla (PCT of the Universidad de Burgos) for technical support and Jos´e Vicente Cuevas Vicario for advice and support with theoretical calculations and Gabriel García-Herbosa for providing us access to CV equipment

Del aprendizaje por competencias a la evaluación formativa de su adquisición: metodología y materiales

Ponencia presentada en: VI Jornadas de Innovación Docente de la UBU, Burgos, 23 y 24 de febrero de 2012, organizadas por el Instituto de Formación e Innovación Educativa-IFIE de la Universidad de Burgo

Distinct mechanism of action for antitumoral neutral cyclometalated Pt(II)-complexes bearing antifungal imidazolyl-based drugs

Three neutral Pt(II) complexes containing 1-Methylimidazole and the antifungal imidazolyl drugs Clotrimazole and Bifonazole have been prepared. The general formula of the new derivatives is [Pt(κ2-(C^N)Cl(L)], where C^N stands for ppy = 2-phenylpyridinate, and L = 1-Methylimidazole (MeIm) for [Pt-MeIm]; L = Clotrimazole (CTZ) for [Pt-CTZ] and L = Bifonazole (BFZ) for [Pt-BFZ]). The complexes have been completely characterized in solution and the crystal structures of [Pt-BFZ] and [Pt-CTZ] have been resolved. Complexes [Pt-MeIm] and [Pt-BFZ] present higher cytotoxicity than cisplatin in SW480 (colon adenocarcinoma), A549 (lung adenocarcinoma) and A2780 (ovarian cancer) cell lines. [Pt-MeIm] shows the highest accumulation in A549 cells, in agreement with its inability to interact with serum albumin. By contrast, [Pt-CTZ] and [Pt-BFZ] interact with serum proteins, a fact that reduces their bioavailability. The strongest interaction with bovine serum albumin (BSA) is found for [Pt-BFZ], which is the least internalized inside the cells. All the complexes are able to covalently interact with DNA. The most cytotoxic complexes, [Pt-MeIm] and [Pt-BFZ] induce cellular accumulation in G0/G1 and apoptosis by a similar pathway, probably involving a reactive oxygen species (ROS) generation mechanism. [Pt-BFZ] turns out to be the most efficient complex regarding ROS generation and causes mitochondrial membrane depolarization, whereas [Pt-MeIm] induces the opposite effect, hyperpolarization of the mitochondrial membrane. On the contrary, the least cytotoxic complex, [Pt-CTZ] cannot block the cell cycle or generate ROS and the mechanism by which it induces apoptosis could be a different one.La Caixa Foundation (LCF/PR/PR12/11070003), Consejería de Educación-Junta de Castilla y León-FEDER (BU042U16-BU305P18), Ministerio de Ciencia, Innovación y Universidades (RTI2018-102040-B-100). M.V. is grateful for the financial support received from the Consejería de Educación-Junta de Castilla y León-FEDER (BU042U16-BU305P18)

Comparative study of the effects of black or white hail nets on the fruit quality of ‘Golden Delicious’ apples

Introduction. The use of hail nets to protect apples during development and maturation on the tree is very common in Mexico. This practice can cause changes in fruit quality and aroma composition. The effects of the hail net color on the quality and aroma volatile production of apple cultivated in Chihuahua, Mexico, were evaluated. Materials and methods. ‘Golden Delicious’ apple trees were covered with white or black hail nets. Apple samples were harvested weekly from August to early October, and analyzed for weight, axial and equatorial diameters, color (°Hue), firmness, total soluble solids (TSS), acidity, ethylene production (EC), and aroma volatile composition. The photosynthetically available radiation (PAR) was measured every ten days under each hail net and outside. Results and discussion. Apple quality was affected by hail net color. Black hail nets delayed maturation and quality development of apples by one week when compared with white hail nets. The PAR values were 18% lower under black nets than under white nets. Quality parameters at commercial harvest (162 days after full bloom) showed that white-net apples presented 7% lower firmness, 11.1% less acidity, 8.3% higher TSS and a more developed yellow color, when compared with black-net apples. In addition, white-net apples presented higher contents of the main aroma compounds (in μg L-1) 1-hexanol (8.09 vs. 4.38), 2-methyl-1-butanol (6.24 vs. 2.65), and 2-methyl-butyl acetate (0.47 vs. 0.16). At the same maturity stage (beginning of the climacteric rise), no difference was found between white- and black-net apples in TSS, acidity, firmness and aromatic compounds. Conclusion. Hail net functionality goes beyond protecting orchards from hail damage; hail net color affects the apple maturation rate, quality and aroma volatile production

Desarrollo de un manual de trabajo para el apoyo de las prácticas conjuntas de prevención de riesgos laborales

Realizado en la Escuela Politécnica Superior, por 7 profesores del centro. El objetivo era la potenciación de las prácticas de las asignaturas de prevención de riesgos, a través de la creación de un material didáctico escrito adecuado para dichas prácticas y la mejora del material existente en el laboratorio, con la adquisición de accesorios que permitieran la realización de nuevas prácticas. El proyecto se ha desarrollado en 7 fases: 1. Recopilación y actualización de documentación y normativa, relativa a la prevención de riesgos; 2. Análisis de los aparatos y herramientas existentes en el mercado sobre prevención; 3. Elaboración de los manuales; 4.Programación y elaboración de las prácticas; 5. Realización de unas prácticas iniciales que sirvan de ejemplo; 6. Revisión; 7. Elaboración de la documentación final. Dentro de la documentación elaborada se distingue una parte con guiones para la práctica y otra con el procedimiento de uso de los aparatos. El resultado ha sido satisfactorio y se sigue usando esta documentación para la realización de las prácticas.Junta de Castilla y León. Consejería de educación y culturaCastilla y LeónJunta de Castilla y León. Consejería de Educación y Cultura; Monasterio de Nuestra Señora de Prado. Autovía Puente Colgante, s. n.; 47071 Valladolid; Tel. +34983411881; Fax +34983411939; [email protected]