Design, Synthesis and Evaluation of Chromo-fluorogenic Probes for Contaminating Species

The present PhD thesis entitled “Design, Synthesis and Evaluation of Chromofluorogenic Probes for Contaminating Species” is focused on the development of new chromo-fluorogenic sensors based on the principles of molecular recognition. The first part of this thesis is focused on the design and synthesis of suitable organic compounds as sensors for metal cations. The selected sensing paradigm was the binding site-signalling subunit approach. The synthetized receptors employs a chromophore (fluorescein or BODIPY) skeleton as signalling subunit and it is functionalized with aminoethoxy moieties as binging site; the metal coordination reduces the electron-donating ability of the nitrogen atom conjugated to the chromophore resulting in optical changes noticeable to the naked-eye. The sensing behavior is highly selective to trivalent cations (Fe3+, Al3+ and Cr3+) with remarkable limits of detection. The receptors based on BODIPYdyes retain the sensing abilities in mixed aqueous solutions. The remaining chapters of the thesis are centered in the detection and removal of nerve agents surrogates. The design, synthesis, characterization and application of new BODIPY chemosensors were studied. These chemosensors were designed containing different reactive sites in order to avoid interferences produced by acids or hydrolysis products, and also be able to distinguish between the different G-nerve agent mimics (DCNP and DFP). The BODIPY-probes allows screening of nerve agent surrogates with remarkable limits of detection and optical changes noticeable to the naked-eye. The sensing abilities are retained in solid support, allowing practical application in real-time monitoring by simple colorimetric tests. The displacement assay approach has been used to develop a selective sensor for V-nerve agent surrogates versus G-type. For this purpose, two Eu3+ and Au3+ BODIPY-complexes were prepared. In this case, V-surrogate is capable of coordinate the metallic center, releasing the BODIPY ligand. This causes a change in the optical properties visible to the naked-eye. Finally, the use of supramolecular-based organocatalyst for destruction of OP nerve agent surrogates was studied. Hydrolysis studies were performed in presence of 1,3-diindolylureas and thioureas, amines, aminoalcohol and glycols. Addition of catalyst enhances the electrophilic character of the P atom, and the final nucleophilic attack of water that results in the formation of the corresponding less toxic organophosphate derivatives, thus higher hydrolysis rates are obtained.Barba Bon, A. (2014). Design, Synthesis and Evaluation of Chromo-fluorogenic Probes for Contaminating Species [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/48521TESI

El comportamiento violento en los grupos: El caso de los grupos coercitivos y los ultras en el fútbol

Treball Final de Grau en Criminologia i Seguretat. Codi: CS1044. Curs 2013-2014Los miembros que componen un determinado grupo comparten normas, valores, formas de percibir la sociedad, actitudes, etc. Se forman bien porque de manera individual consideran que con su pertenencia verán satisfechas sus necesidades, bien porque el sujeto siente atracción hacia sus miembros o hacia las actividades que el grupo realiza, porque considera valiosos los objetivos que persigue o por el simple hecho de sentirse integrado en un grupo con otros miembros con los que compartir actividades. Para la consecución de sus objetivos se establece una estructura, ya sea de manera formal o informal, en la que se establecen las diferentes posiciones y funciones de los miembros dentro del grupo u las pautas o reglas de conducta. En grupos violentos los miembros del grupo están dominados por líderes autoritarios. La obediencia ciega hacia éstos y los procesos de influencia grupal provocan que los individuos se dejen llevar por las normas del grupo, se conformen con las conductas realizadas por la mayoría y que terminen pensando que la norma del grupo es la única vía de hacer las cosas. En los grupos coercitivos se consigue esa dominación mediante la utilización de técnicas manipulativas dirigidas a controlar la voluntad de los adeptos e imponerles su ideología por medio de un proceso de adoctrinamiento en el que se aísla al sujeto de su entorno anterior para que su única influencia sea la que marca el grupo, adoptándose así la identidad de éste. En el caso de los ultras en el fútbol, en cambio, comenzaron adoptando esas posturas violentas como actos de rebeldía social o como instrumento para reivindicar posiciones políticas, sin embargo la violencia se ha normalizado hasta el punto de su utilización como algo que genera satisfacción a sus miembros, una pauta de conducta que hay que seguir para formar parte del mismo y de la que no te puedes desviar.Members of a particular group shared norms, values, ways of perceiving the society, attitudes, etc... The groups are well formed because individually consider that with their belonging will see their needs satisfied, either because the individual is attracted by the members or is attracted by the activities realized by the group; or because is considered valuable the objectives pursued, or simply because feeling integrated into a group with other people who share time and activities. To achieve their objectives a structure is established, either in a formal or informal manner, where the different positions are established as well as the roles of the members within the group and the guidelines or rules of conduct. In violent groups, members are dominated by autoritary leaders. The mindless obedience towards these leaders and the influence group processes cause the individuals get carried away by the group norms, the individuals are conformed with the behaviors of the majority and they finish thinking that the rule of the group is the only route of doing things. In coercive groups such domination is achieved through the use of manipulative techniques designed to control the will of the followers and impose their ideology through a process of indoctrination in which the individual is isolated from his former environment so its unique influence is which marks the group, thereby adapting the identity of the group. In the case of ultra-groups in football, in contrast, they started adopting these violent attitude as acts of social revelation or as an instrument to vindicate political positions, nevertheless violence in these ultra-groups has been normalized to the point of use as something that generates its members satisfaction, a pattern of conduct that should be followed to be part of the group and that cannot divert

Stability and pKa Modulation of Aminophenoxazinones and Their Disulfide Mimics by Host-Guest Interaction with Cucurbit[7]uril. Direct Applications in Agrochemical Wheat Models

Aqueous solubility and stability often limit the application of aminophenoxazinones and their sulfur mimics as promising agrochemicals in a sustainable agriculture inspired by allelopathy. This paper presents a solution to the problem using host-guest complexation with cucurbiturils (CBn). Computational studies show that CB7 is the most suitably sized homologue due to its strong affinity for guest molecules and its high water solubility. Complex formation has been studied by direct titrations monitored using UV-vis spectroscopy, finding a preferential interaction with protonated aminophenoxazinone species with high binding affinities (CB7 center dot APOH+ , Ka = (1.85 +/- 0.37) x 106 M-1; CB7 center dot DiS-NH3+ , Ka = (3.91 +/- 0.53) x 104 M-1; and DiS-(NH3+)2 , Ka= (1.27 +/- 0.42) x 105M-1). NMR characterization and stability analysis were also performed and revealed an interesting pKa modulation and stabilization by cucurbiturils (2-amino-3H-phenoxazin-3-one (APO), pKa = 2.94 +/- 0.30, and CB7 center dot APO, pKa = 4.12 +/- 0.15; 2,2 '-disulfanediyldianiline (DiS-NH2), pKa = 2.14 +/- 0.09, and CB7 center dot DiS-NH2 , pKa = 3.26 +/- 0.09), thus favoring applications in different kinds of crop soils. Kinetic studies have demonstrated the stability of the CB7 center dot APO complex at different pH media for more than 90 min. An in vitro bioassay with etiolated wheat coleoptiles showed that the bioactivity of APO and DiS-NH2 is enhanced upon complexation

Biasing hydrogen bond donating host systems towards chemical warfare agent recognition

A series of neutral ditopic and negatively charged, monotopic host molecules have been evaluated for their ability to bind chloride and dihydrogen phosphate anions, and neutral organophosphorus species dimethyl methylphosphonate (DMMP), pinacolyl methylphosphonate (PMP) and the chemical warfare agent (CWA) pinacolyl methylphosphonofluoridate (GD, soman) in organic solvent via hydrogen bonding. Urea, thiourea and boronic acid groups are shown to bind anions and neutral guests through the formation of hydrogen bonds, with the urea and thiourea groups typically exhibiting higher affinity interactions. The introduction of a negative charge on the host structure is shown to decrease anion affinity, whilst still allowing for high stability host-GD complex formation. Importantly, the affinity of the host for the neutral CWA GD is greater than for anionic guests, thus demonstrating the potential for selectivity reversal based on charge repulsion

Detection and remediation of organophosphorus compounds by oximate containing organogels

A series of supramolecular diamide organogels containing a reactive compound for the remediation of organophosphorus (OP) species, in particular OP chemical warfare agents (CWAs), has been prepared in DMSO. The organogels have been found to absorb, encapsulate and decontaminate various OP CWA simulants in situ. At high simulant concentrations the gels also undergo a gel–sol transition releasing high local concentrations of remediation agent

Selective chromo-fluorogenic detection of trivalent cations in aqueous environments using a dehydration reaction

[EN] Trivalent cations (Al3+, Fe3+, Cr3+, As3+, In3+ and Ga3+) induced a dehydration reaction of a chemodosimeter in water that is coupled with colour and emission changes.Financial support from the Spanish Government and FEDER funds (Project MAT2015-64139-C4-1) and the Generalitat Valencia (Project PROMETEO II/2014/047) is gratefully acknowledged. M. L. P. is grateful to the Generalitat Valenciana for her Santiago Grisolia grant.Lo-Presti, M.; El Sayed Shehata Nasr, S.; Martínez-Máñez, R.; Costero, AM.; Gil, S.; Parra, M.; Sancenón Galarza, F. (2016). Selective chromo-fluorogenic detection of trivalent cations in aqueous environments using a dehydration reaction. New Journal of Chemistry. 40(11):9042-9045. https://doi.org/10.1039/c6nj01957aS90429045401

Multiple effects of toxins isolated from Crotalus durissus terrificus on the hepatitis C virus life cycle

Hepatitis C virus (HCV) is one of the main causes of liver disease and transplantation worldwide. Current therapy is expensive, presents additional side effects and viral resistance has been described. Therefore, studies for developing more efficient antivirals against HCV are needed. Compounds isolated from animal venoms have shown antiviral activity against some viruses such as Dengue virus, Yellow fever virus and Measles virus. In this study, we evaluated the effect of the complex crotoxin (CX) and its subunits crotapotin (CP) and phospholipase A2 (PLA2-CB) isolated from the venom of Crotalus durissus terrificus on HCV life cycle. Huh 7.5 cells were infected with HCVcc JFH-1 strain in the presence or absence of these toxins and virus was titrated by focus formation units assay or by qPCR. Toxins were added to the cells at different time points depending on the stage of virus life cycle to be evaluated. The results showed that treatment with PLA2-CB inhibited HCV entry and replication but no effect on HCV release was observed. CX reduced virus entry and release but not replication. By treating cells with CP, an antiviral effect was observed on HCV release, the only stage inhibited by this compound. Our data demonstrated the multiple antiviral effects of toxins from animal venoms on HCV life cycle

Binding of chemical warfare agent simulants as guests in a coordination cage: contributions to binding and a fluorescence-based response.

Cubic coordination cages act as competent hosts for several alkyl phosphonates used as chemical warfare agent simulants; a range of cage/guest structures have been determined, contributions to guest binding analysed, and a fluorescent response to guest binding demonstrated

Fluorescent Discrimination between Traces of Chemical Warfare Agents and Their Mimics

An array of fluorogenic probes is able to discriminate between nerve agents, sarin, soman, tabun, VX and their mimics, in water or organic solvent, by qualitative fluorescence patterns and quantitative multivariate analysis, thus making the system suitable for the inthe- field detection of traces of chemical warfare agents as well as to differentiate between the real nerve agents and other related compounds.Ministerio de Economía y Competitividad, Spain (Project CTQ2012- 31611), Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo (Project BU246A12-1), the European Commission, Seventh Framework Programme (Project SNIFFER FP7-SEC-2012-312411) and the Swedish Ministry of Defence (no. A403913