Molecular computations for reactions and phase transitions: applications to protein stabilization, hydrates and catalysis

In this work we have made significant contributions in three different areas of interest: therapeutic protein stabilization, thermodynamics of natural gas clathrate-hydrates, and zeolite catalysis. In all three fields, using our various computational techniques, we have been able to elucidate phenomena that are difficult or impossible to explain experimentally. More specifically, in mixed solvent systems for proteins we developed a statistical-mechanical method to model the thermodynamic effects of additives in molecular-level detail. It was the first method demonstrated to have truly predictive (no adjustable parameters) capability for real protein systems. We also describe a novel mechanism that slows protein association reactions, called the “gap effect.” We developed a comprehensive picture of methioine oxidation by hydrogen peroxide that allows for accurate prediction of protein oxidation and provides a rationale for developing strategies to control oxidation. The method of solvent accessible area (SAA) was shown not to correlate well with oxidation rates. A new property, averaged two-shell water coordination number (2SWCN) was identified and shown to correlate well with oxidation rates. Reference parameters for the van der Waals Platteeuw model of clathrate-hydrates were found for structure I and structure II. These reference parameters are independent of the potential form (unlike the commonly used parameters) and have been validated by calculating phase behavior and structural transitions for mixed hydrate systems. These calculations are validated with experimental data for both structures and for systems that undergo transitions from one structure to another. This is the first method of calculating hydrate thermodynamics to demonstrate predictive capability for phase equilibria, structural changes, and occupancy in pure and mixed hydrate systems. We have computed a new mechanism for the methanol coupling reaction to form ethanol and water in the zeolite chabazite. The mechanism at 400°C proceeds via stable intermediates of water, methane, and protonated formaldehyde.

Cognitive appraisals, emotional reactions, and their associations with three forms of peer-victimization

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Media bias and central bank response. Evidence from the nominal exchange rate behavior in Colombia

Since 1991 Colombia has had a market-determined Peso - US Dollar Nominal Exchange Rate (NER), after more than 20 years of controlled and multiple exchange rates. The behavior (revaluation / devaluation) of the NER is constantly reported in news, editorials and op-eds of major newspapers of the nation with particular attention to revaluation. The uneven reporting of revaluation episodes can be explained by the existence of an interest group particulary affected by revaluation, looking to increase awareness and sympathy for help from public institutions. Using the number of news and op-eds from a major Colombian newspaper, it is shown that there is an over-reporting of revaluation episodes in contrast to devaluation ones. Secondly, using text analysis upon the content of the news, it is also shown that the words devaluation and revaluation are far apart in the distribution of words within the news; and revaluation is highly correlated with words related to: public institutions, exporters and the need of assistance. Finally it is also shown that the probability of the central bank buying US dollars to lessen revaluation effects increases with the number of news; even though the central bank allegedly intervenes in the exchange rate market only to tame volatility or accumulate international reserves.

A simple test of momentum in foreign exchange markets

This study proposes a new method for testing for the presence of momentum in nominal exchange rates, using a probabilistic approach. We illustrate our methodology estimating a binary response model using information on local currency / US dollar exchange rates of eight emerging economies. After controlling for important variables a§ecting the behavior of exchange rates in the short-run, we show evidence of exchange rate inertia; in other words, we Önd that exchange rate momentum is a common feature in this group of emerging economies, and thus foreign exchange traders participating in these markets are able to make excess returns by following technical analysis strategies. We Önd that the presence of momentum is asymmetric, being stronger in moments of currency depreciation than of appreciation. This behavior may be associated with central bank intervention

Modelling official and parallel exchange rates in Colombia under alternative regimes: a non-linear approach

We examine the long-run relationship between the parallel and the official exchange rate in Colombia over two regimes; a crawling peg period and a more flexible crawling band one. The short-run adjustment process of the parallel rate is examined both in a linear and a nonlinear context. We find that the change from the crawling peg to the crawling band regime did not affect the long-run relationship between the official and parallel exchange rates, but altered the short-run dynamics. Non-linear adjustment seems appropriate for the first period, mainly due to strict foreign controls that cause distortions in the transition back to equilibrium once disequilibrium occurs

Piecemeal Oligopoly, Exchange Rate Uncertainty, and Trade Policy.

Este artículo analiza el efecto sistemático de la volatilidad de la tasa de cambio, cuando un gobierno local debe evaluar políticas comerciales estratégicas lineales y cuadráticas. Este ejercicio se realiza para modelos de mercado Cournot y Bertran. El modelo prueba que tanto el esquema lineal como el cuadrático tienen el mismo efecto sobre el bienestar social de los países, y que la volatilidad de la tasa de cambio domestica lleva a los gobiernos a reducir los subsidios a las exportaciones o bajan los impuestos a las exportaciones, de acuerdo a la variable estratégica elegida por las firmas. La tasa de cambio extranjera tiene diferentes efectos dependiendo de si las firmas producen bajos rendimientos a escalas constantes o decrecientes.

London, a school exchange : unidad didáctica.

Sugiere material complementario

Material changes and reactions.

En el mundo que nos rodea existen múltiples ejemplos de sustancias que cambian y producen nuevas sustancias. El estudio de estos cambios en los materiales y de las reacciones que se producen entre sí es parte de la química.Este texto nos permite conocer cómo ésta se desarrolla no sólo en los laboratorios y entre científicos, sino también en fábricas y plantas químicas, y con múltiples aplicaciones: en la fabricación de fibras sintéticas para los tejidos, de explosivos para los fuegos artificiales, de disolventes para las pinturas, de fertilizantes para los cultivos y de medicamentos para tratar enfermedades.

The reactions of metals.

Explica que son los metales, sus propiedades, las aleaciones, y las reacciones que se producen con otros materiales, lo que los científicos llaman reactividad. Está adaptado a alumnos de once a catorce años, que cursan la etapa 3 (Key Stage 3)del curriculo nacional inglés.

Organizational injustice : Third parties’ reactions to mistreatmentof employee

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Interpretation, emotional reactions and daily life implications of hallucination-like experiences in clinical and nonclinical populations

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Destabilizing Mutations Alter the Hydrogen Exchange Mechanism in Ribonuclease A

The effect of strongly destabilizing mutations, I106A and V108G of Ribonuclease A (RNase A), on its structure and stability has been determined by NMR. The solution structures of these variants are essentially equivalent to RNase A. The exchange rates of the most protected amide protons in RNase A (35ºC), the I106A variant (35ºC), and the V108G variant (10ºC) yield stability values of 9.9, 6.0, and 6.8 kcal/mol, respectively, when analyzed assuming an EX2 exchange mechanism. Thus, the destabilization induced by these mutations is propagated throughout the protein. Simulation of RNase A hydrogen exchange indicates that the most protected protons in RNase A and the V108G variant exchange via the EX2 regime, whereas those of I106A exchange through a mixed EX1 1 EX2 process. It is striking that a single point mutation can alter the overall exchange mechanism. Thus, destabilizing mutations joins high temperatures, high pH and the presence of denaturating agents as a factor that induces EX1 exchange in proteins. The calculations also indicate a shift from the EX2 to the EX1 mechanism for less protected groups within the same protein. This should be borne in mind when interpreting exchange data as a measure of local stability in less protected regions

Managanese and dicopper complexes for bioinspired oxidation reactions: catalytic and mechanistic studies on C-H and C=C oxidations

Enzymes are high-weight molecules which catalyze most of the metabolic processes in living organisms. Very often, these proteins contain one or more 1st row transition metal ions in their active center (Fe, Cu, Co, Mn, Zn, etc.), and are known as metalloenzymes or metalloproteins. Among these, metalloenzymes that activate molecular oxygen and use it as terminal oxidant stand out because of the wide range of catalyzed reactions and their exquisite selectivity. In this PhD dissertation we develop low-weight synthetic bioinspired complexes that can mimic structural and/or functional features of the active center of oxigenases. In the first part, we describe the use of unsymmetric dinuclear Cu complexes which are capable of performing the oxidation of phenols and phenolates in a analogous manner of the tyrosinase protein. In the second part, we describe the use of mononuclear manganese complexes in the oxidation of alcanes and alquenes.

Rhodium(I) catalyzed [2+2+2] cycloaddition reactions: experimental and theoretical studies

The [2+2+2] cycloaddition reaction involves the formation of three carbon-carbon bonds in one single step using alkynes, alkenes, nitriles, carbonyls and other unsaturated reagents as reactants. This is one of the most elegant methods for the construction of polycyclic aromatic compounds and heteroaromatic, which have important academic and industrial uses. The thesis is divided into ten chapters including six related publications. The first study based on the Wilkinson’s catalyst, RhCl(PPh3)3, compares the reaction mechanism of the [2+2+2] cycloaddition process of acetylene with the cycloaddition obtained for the model of the complex, RhCl(PH3)3. In an attempt to reduce computational costs in DFT studies, this research project aimed to substitute PPh3 ligands for PH3, despite the electronic and steric effects produced by PPh3 ligands being significantly different to those created by PH3 ones. In this first study, detailed theoretical calculations were performed to determine the reaction mechanism of the two complexes. Despite some differences being detected, it was found that modelling PPh3 by PH3 in the catalyst helps to reduce the computational cost significantly while at the same time providing qualitatively acceptable results. Taking into account the results obtained in this earlier study, the model of the Wilkinson’s catalyst, RhCl(PH3)3, was applied to study different [2+2+2] cycloaddition reactions with unsaturated systems conducted in the laboratory. Our research group found that in the case of totally closed systems, specifically 15- and 25-membered azamacrocycles can afford benzenic compounds, except in the case of 20-membered azamacrocycle (20-MAA) which was inactive with the Wilkinson’s catalyst. In this study, theoretical calculations allowed to determine the origin of the different reactivity of the 20-MAA, where it was found that the activation barrier of the oxidative addition of two alkynes is higher than those obtained for the 15- and 25-membered macrocycles. This barrier was attributed primarily to the interaction energy, which corresponds to the energy that is released when the two deformed reagents interact in the transition state. The main factor that helped to provide an explanation to the different reactivity observed was that the 20-MAA had a more stable and delocalized HOMO orbital in the oxidative addition step. Moreover, we observed that the formation of a strained ten-membered ring during the cycloaddition of 20-MAA presents significant steric hindrance. Furthermore, in Chapter 5, an electrochemical study is presented in collaboration with Prof. Anny Jutand from Paris. This work allowed studying the main steps of the catalytic cycle of the [2+2+2] cycloaddition reaction between diynes with a monoalkyne. First kinetic data were obtained of the [2+2+2] cycloaddition process catalyzed by the Wilkinson’s catalyst, where it was observed that the rate-determining step of the reaction can change depending on the structure of the starting reagents. In the case of the [2+2+2] cycloaddition reaction involving two alkynes and one alkene in the same molecule (enediynes), it is well known that the oxidative coupling may occur between two alkynes giving the corresponding metallacyclopentadiene, or between one alkyne and the alkene affording the metallacyclopentene complex. Wilkinson’s model was used in DFT calculations to analyze the different factors that may influence in the reaction mechanism. Here it was observed that the cyclic enediynes always prefer the oxidative coupling between two alkynes moieties, while the acyclic cases have different preferences depending on the linker and the substituents used in the alkynes. Moreover, the Wilkinson’s model was used to explain the experimental results achieved in Chapter 7 where the [2+2+2] cycloaddition reaction of enediynes is studied varying the position of the double bond in the starting reagent. It was observed that enediynes type yne-ene-yne preferred the standard [2+2+2] cycloaddition reaction, while enediynes type yne-yne-ene suffered β-hydride elimination followed a reductive elimination of Wilkinson’s catalyst giving cyclohexadiene compounds, which are isomers from those that would be obtained through standard [2+2+2] cycloaddition reactions. Finally, the last chapter of this thesis is based on the use of DFT calculations to determine the reaction mechanism when the macrocycles are treated with transition metals that are inactive to the [2+2+2] cycloaddition reaction, but which are thermally active leading to new polycyclic compounds. Thus, a domino process was described combining an ene reaction and a Diels-Alder cycloaddition.