Dynamics and structure of liquids under special conditions: water confined in giant polyoxometalates and co2-brine mixtures

L'estructura i la dinàmica dels líquids varien sota determinades condicions, tals com sota confinament o en presència d'ions. Aquesta tesi es divideix en dues parts. En la primera part, s'han estudiat l'estructura i la dinàmica d'aigua confinada en polyoxomolibdats gegants, per mitjà de simulacions de dinàmica molecular (DM) a condicions normals de temperatura i pressió. Els resultats obtinguts mostren que l'aigua tendeix a organitzar-se en capes concèntriques de la família de les buckyball. Les posicions d'aquestes capes coincideixen amb resultats experimentals de raigs X per aquest sistema a baixa temperatura. S'han calculat un gran nombre de propietats estructurals i dinàmiques, algunes de les quals s'han comparat amb dades experimentals i de simulació per micel•les reverses de grandària similar amb un resultat satisfactori. La segona part de la tesi es centra en el càlcul de la difussivitat del diòxid de carboni (CO2) en salmorra sota les condiciones termodinàmiques representatives d’aqüífers salins subterranis mitjançant simulacions de dinàmica molecular. S'han calculat els coeficients de difusió màssics i d'autodifusió del CO2, la conductivitat elèctrica de la barreja, així com els temps de relaxació rotacional del CO2 per totes les condicions. Aquests resultats constitueixen la primera estimació de coeficients de difusió màssics i temps de relaxació rotacional del CO2 en aqüífers salins subterranis.The structure and dynamics of liquids are distorted under special conditions, such as under confinement, or in the presence of ions. This thesis is divided into two parts. In the first part, we have studied the structure and dynamics of water confined in giant polyoxomolybdate molecular clusters by means of molecular dynamics (MD) simulations at ambient conditions. We observe that water organizes in concentric layered structures of the buckyball family, which agree with X-ray data for these systems at low temperature. Several structural and dynamical data are provided and compared to experimental and theoretical analyses for reverse micelles of similar size, where qualitative agreement is observed. The second part of the thesis is devoted to the calculation of the diffusivity of carbon dioxide (CO2) in brine under the thermodynamic conditions representative of deep saline aquifers through MD simulations. We have calculated CO2 mass and self diffusion coefficients, electrical conductivities, as well as rotational relaxation times. These results are the first estimation of mass diffusion and rotational relaxation times of CO2 in deep saline aquifers

La pintura mural a la Catalunya interior al segle XX

La pintura mural en el siglo XX en la Catalunya interior definió un período prolífico y productivo durante la segunda mitad del siglo, debido al proceso de reconstrucción de la postguerra y a la recuperación de la disciplina en tiempos de la Transición democrática. Tenemos pocos ejemplos del Modernismo y del Novecentismo y solamente podemos hablar de algunos artistas emblemáticos de dichas corrientes que, como Francesc Galí, Miquel Farré o Josep Obiols, realizaron proyectos murales en una cronología posterior. Si lo comparamos con el muralismo de postguerra, el impacto global de dichos precedentes resulta desproporcionado. Los años cincuenta, especialmente, significaron un salto cuantitativo que se desarrolló por la geografía de Lleida a cargo de los artistas plásticos, que intentaban profesionalizarse, como fue el caso de Jaume Minguell, Lluís Trepat, Miquel Roig Nadal o Víctor P. Pallarés. En los años ochenta, una vez pasado el proceso reconstructivo, el muralismo perdió su presencia, hasta que el pintor Josep Minguell delimitó, a través de su reivindicación ética y estética, una reconstrucción disciplinaria

Ionization Energies and Redox Potentials of Hydrated Transition Metal Ions: Evaluation of Domain-Based Local Pair Natural Orbital Coupled Cluster Approaches

Hydrated transition metal ions are prototypical systems that can be used to model properties of transition metals in complex chemical environments. These seemingly simple systems present challenges for computational chemistry and are thus crucial in evaluations of quantum chemical methods for spin-state and redox energetics. In this work, we explore the applicability of the domain-based pair natural orbital implementation of coupled cluster (DLPNO-CC) theory to the calculation of ionization energies and redox potentials for hydrated ions of all first transition row (3d) metals in the 2+/3+ oxidation states, in connection with various solvation approaches. In terms of model definition, we investigate the construction of a minimally explicitly hydrated quantum cluster with a first and second hydration layer. We report on the convergence with respect to the coupled cluster expansion and the PNO space, as well as on the role of perturbative triple excitations. A recent implementation of the conductor-like polarizable continuum model (CPCM) for the DLPNO-CC approach is employed to determine self-consistent redox potentials at the coupled cluster level. Our results establish conditions for the convergence of DLPNO-CCSD(T) energetics and stress the absolute necessity to explicitly consider the second solvation sphere even when CPCM is used. The achievable accuracy for redox potentials of a practical DLPNO-based approach is, on average, 0.13 V. Furthermore, multilayer approaches that combine a higher-level DLPNO-CCSD(T) description of the first solvation sphere with a lower-level description of the second solvation layer are investigated. The present work establishes optimal and transferable methodological choices for employing DLPNO-based coupled cluster theory, the associated CPCM implementation, and cost-efficient multilayer derivatives of the approach for open-shell transition metal systems in complex environments

3,4-Methylenedioxy-methamphetamine induces in vivo regional up-regulation of central nicotinic receptors in rats and potentiates the regulatory effects of nicotine on these receptors

Nicotine (NIC), the main psychostimulant compound of smoked tobacco, exerts its effects through activation of central nicotinic acetylcholine receptors (nAChR), which become up-regulated after chronic administration. Recent work has demonstrated that the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) has affinity for nAChR and also induces up-regulation of nAChR in PC 12 cells. Tobacco and MDMA are often consumed together. In the present work we studied the in vivo effect of a classic chronic dosing schedule of MDMA in rats, alone or combined with a chronic schedule of NIC, on the density of nAChR and on serotonin reuptake transporters. MDMA induced significant decreases in [3H]paroxetine binding in the cortex and hippocampus measured 24 h after the last dose and these decreases were not modified by the association with NIC. In the prefrontal cortex, NIC and MDMA each induced significant increases in [3H]epibatidine binding (29.5 and 34.6%, respectively) with respect to saline-treated rats, and these increases were significantly potentiated (up to 72.1%) when the two drugs were associated. Also in this area, [3H]methyllycaconitine binding was increased a 42.1% with NIC + MDMA but not when they were given alone. In the hippocampus, MDMA potentiated the a7 regulatory effects of NIC (raising a 25.5% increase to 52.5%) but alone was devoid of effect. MDMA had no effect on heteromeric nAChR in striatum and a coronal section of the midbrain containing superior colliculi, geniculate nuclei, substantia nigra and ventral tegmental area. Specific immunoprecipitation of solubilised receptors suggests that the up-regulated heteromeric nAChRs contain a4 and b2 subunits. Western blots with specific a4 and a7 antibodies showed no significant differences between the groups, indicating that, as reported for nicotine, up-regulation caused by MDMA is due to post-translational events rather than increased receptor synthesis

Interacció dels derivats amfetamínics amb els receptors nicotínics: Aspectes moleculars i funcionals

[spa] En treballs anteriors del nostre grup de recerca es va demostrar que l’antagonista específic del receptor nicotínic α7, metillicaconitina (MLA), inhibia in vitro la producció d’espècies reactives d’oxigen (EROS) i protegia de la neurotoxicitat in vivo induïda per metamfetamina (METH) i per la 3,4-metilendioxi-N-metamfetamina (MDMA). En aquesta tesi, es descriu un nou mecanisme d’acció dels derivats amfetamínics. Mitjançant assajos de fixació de radiolligands, es va comprovar que ambdós derivats amfetamínics competien amb els radiolligands específics dels receptors nicotínics α7 ([3H]Metillicaconitina), i dels heteromèrics ([3H]Epibatidina), el que indicava que en les cèl ·lules PC12, el nostre model experimental, i també en una preparació de cervell total de ratolí, aquestes substàncies interaccionaven directament amb els receptors nicotínics. L’MDMA mostrava més afinitat per ambdós subtipus de receptors. Està descrit que el tractament crònic amb nicotina provoca un augment en la densitat de receptors nicotínics tan in vivo com in vitro en cèl ·lules PC12. Ambdós derivats amfetamínics van provocar una regulació a l’alça dels dos subtipus de receptors ja a les 6 hores de pretractament. A la vegada, in vivo, l’MDMA i la Nicotina van provocar la regulació a l’alça que va ser potenciada per la seva associació en determinades zones cerebrals on s’expressen cada subtipus de nAChR. De l’estudi dels mecanismes implicats en aquesta regulació a l’alça, mitjançant inhibidors a diferents nivells, es va concluir que, igual com passa amb la nicotina, es produeixen a nivell postraduccional. A nivell funcional, vam determinar que aquests derivats amfetamínics eren capaços d’activar els receptors nicotínics i, d’acord amb les hipòtesis de treballs anteriors, induir una entrada de calci i de sodi que podria estar implicada en els esdeveniments que comportarien la seva neurotoxicitat. Per una banda, l’MDMA i la METH es van comportar com agonistes parcials dels nAChR α7 induïnt un increment de Ca2+ citosòlic. Per altra banda, l’MDMA es va comportar com antagonista dels nAChR heteromèrics i la METH com agonista parcial induint l’entrada de Na+ de la mateixa manera, el qual explicaria diferències a nivell de dependència, ja que els nAChR α4β2 estan implicats en la via mesolímbica o de recompensa. Paral ·lelament a l’increment de fixació de radiolligands, es va determinar que la preincubació amb MDMA indueix un increment en la resposta per activació de receptors nicotínics, demostrant que l’ MDMA també indueix regulació a l’alça funcional. Alhora, es va observar que la preincubació de les cèl ·lules durant 24 hores amb MDMA dona lloc a un increment perllongat dels nivells basals de Ca2+, el qual indica que l’MDMA inhibeix la desensibilització dels receptors i fa que entri calci durant un temps més llarg. Aquesta entrada persistent podria estar implicada en fenòmens de neurotoxicitat ja que va seguida de l’activació de vies dependents de calci com la calpaïna i la caspasa-3.[eng] During the last years, our emphasis has focused in the study of the neurotoxic effects of MDMA and methamphetamine (METH) on central nervous system and their pharmacological prevention. It has been demonstrated that these amphetamine derivatives produce oxygen species (ROS) in an in vitro model of synaptosomes. In previous works, we demonstrated that blockade of alpha7 nicotinic receptors with methyllycaconitine (MLA) prevented ROS production induced by MDMA and METH, consequently the alpha7 receptor would be involved in the neurotoxicity induced by these drugs. Studies at molecular level, using radioligand binding assays, showed the interaction of METH and MDMA with homomeric alpha7 nAChR and heteromeric subtypes of nicotinic receptors, such as aplha4 beta2. In addition, we investigated the effects of pretreatment with METH and MDMA on nAChR densities. We used PC 12 cells as an experimental model due to the fact other authors have similarly utilised them to evaluate the neurotoxicity of amphetamines. Moreover, they not only express nAChR, including the alpha7 subtype, but also provide an in vitro model for the up-regulation of nAChR, which occurs in vivo following chronic exposure to nicotine. In recent works, we demonstrated in vitro that Ca2+ chelation with EGTA prevented the production of reactive oxygen species (ROS) to a similar extent as nAChR blockade. This indicates that calcium influx, probably through alpha7 nAChR, is a key step in this process. Consequently, one of the objectives of this work was to use a fluorimetric method to investigate the effect of MDMA on Ca2+ and Na+ levels in cultured PC12 cells and the involvement of different nAChR subtypes and other cell pathways related to Ca2+ mobilization. In addition, we used electrophysiology in transfected Xenopus oocytes to corroborate the effects on alpha7 and alpha4 beta2 nAChR. Moreover, pretreatment with MDMA induced functional upregulation by potentiating the effects of specific nAChR agonists or whether it provoked a persistent Ca2+ increase, leading to calpain, caspase 3, NFκB, GSK-3 and Cyt C activation, which was involved in toxicity

Efficient implementation of the analytical second derivatives of hartree–fock and hybrid DFT energies within the framework of the conductor‐like polarizable continuum model

Calculation of vibrational frequencies for solvated systems is essential to study reactions in complex environments. In this paper, we report the implementation of the analytical self‐consistent field Hessian at the Hartree–Fock and density functional theory levels in the framework of the conductor‐like polarizable continuum model (C‐PCM) into the ORCA quantum chemistry suite. The calculated vibrational frequencies agree very well with those computed through numerical differentiation of the analytical gradients. The deviation between both sets of data is smaller than 3 cm−1 for frequencies larger than 200 cm−1 and smaller than 5 cm−1 for the low‐frequency regime (100 cm−1  −1). The accuracy of the frequencies is not significantly affected by the size of the density functional theory (DFT) integration grid, with a deviation lower than 0.5 cm−1 between data computed with the smallest and that with the largest DFT grid size. The calculation of the analytical Hessian is between 3 and 12 times faster than its numerical counterpart. The C‐PCM terms only add an overhead of 10–30% relative to the gas phase calculations. Finally, for acetone, the (B3LYP) values for the frequency shifts obtained in going from the gas phase to liquid acetone are in agreement with experiment

Effect of the Solute Cavity on the Solvation Energy and its Derivatives within the Framework of the Gaussian Charge Scheme

The treatment of the solvation charges using Gaussian functions in the polarizable continuum model results in a smooth potential energy surface. These charges are placed on top of the surface of the solute cavity. In this article, we study the effect of the solute cavity (van der Waals‐type or solvent‐excluded surface‐type) using the Gaussian charge scheme within the framework of the conductor‐like polarizable continuum model on (a) the accuracy and computational cost of the self‐consistent field (SCF) energy and its gradient and on (b) the calculation of free energies of solvation. For that purpose, we have considered a large set of systems ranging from few atoms to more than 200 atoms in different solvents. Our results at the DFT level using the B3LYP functional and the def2‐TZVP basis set show that the choice of the solute cavity does neither affect the accuracy nor the cost of calculations for small systems (< 100 atoms). For larger systems, the use of a vdW‐type cavity is recommended, as it prevents small oscillations in the gradient (present when using a SES‐type cavity), which affect the convergence of the SCF energy gradient. Regarding the free energies of solvation, we consider a solvent‐dependent probe sphere to construct the solvent‐accessible surface area required to calculate the nonelectrostatic contribution to the free energy of solvation. For this part, our results for a large set of organic molecules in different solvents agree with available experimental data with an accuracy lower than 1 kcal/mol for both polar and nonpolar solvents

Involvement of nicotinic receptors in methamphetamine and MDMA induced neurotoxicity: Pharmacological studies

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/32392During the last years, our emphasis has focused in the study of the neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) on central nervous system and their pharmacological prevention. In the process of this research, we have used a semipurified synaptosomal preparation from striatum of mice or rats as a reliable in vitro model to study reactive oxygen species (ROS) production by these amphetamine derivatives, which is well correlated with their dopaminergic injury in in vivo models. Using this preparation we have demonstrated that blockade of alpha7 nicotinic receptors with methyllycaconitine (MLA) and memantine (MEM) prevents ROS production induced by MDMA and METH. Studies at molecular level showed that both, MDMA and METH, displaced competitively the binding of radioligands for homomeric alpha7 and heteromeric nAChRs, indicating that they can directly interact with them. In all the cases MDMA displayed higher affinity than METH and it was higher for heteromeric than for alpha7 subtype. Preincubation of differentiated PC12 cells with MDMA or METH induces nicotinic acetylcholine receptors (nAChR) up-regulation in a concentration- and time-dependent manner, as many nicotinic ligands do, supporting their functional interaction with nAChRs. Such interaction expands the pharmacological profile of amphetamines and can account for some of their effects

A mechanism for the selective epimerization of the glucose mannose pair by Mo-based compounds: towards catalyst optimization†

The selective C2 epimerization of the glucose/mannose pair on a set of Mo-based catalysts was studied by means of density functional theory. The process, known as the Bilik reaction, encompasses a 1,2 C-shift of the C3 centers at the sugars. Molybdic acid was initially proposed as a catalyst in this reaction, and recent experimental studies have shown that the polyoxometalate (POM) Keggin cluster H3PMo12O40 also presents a good performance. In the present work, we propose a reaction mechanism for the epimerization on the Keggin cluster with different heteroatoms and extend it to a larger POM, H6P2Mo18O62, and the continuous α-MoO3(010) surface. We have found that in the transition state corresponding to the 1,2 C-shift the Mo center acts as an electron buffer that promotes the transformation of the aldehyde group in C1 into an alkoxy group and the C2 alkoxy into an aldehyde group. As a consequence, the activity of Mo-containing compounds can be traced back to the reducibility of the Mo center and a simple microkinetic model illustrates that this descriptor generates an activity volcano. This allows the identification of a new POM that shall be 4.7 times more active than the parent compound. We have thus shown that continuum models linking the properties of molecular cluster-like catalysts and oxide surfaces can be derived and this paves the way towards a unified theory in catalysis