Enzymes are the most proficient catalysts that evolution has developed to assist the chemical reactions that make life possible. By means of molecular simulations the present thesis addresses three aspects of fundamental importance for the enzymatic function: reactivity, dynamics and thermostability. The reactivity studies focuses on phosphoryl transfer reactions, which are involved in a broad range of biological processes. We have studied intermediate pentacoordinated species (phosphoranes) being formed in the course of a nucleophilic substitution at phosphorus with quantum mechanical methods (QM). The striking feature of these compounds is that they can be strongly polarized due to the dative character of the apical bonds. Thus external electric fields can alter the geometry and stability of these compounds to the extent that the reaction mechanism can be modified. Indeed, enzyme active sites exhibit strong electric fields able to introduce such effects. The knowledge acquired in model systems of pentacoordinated phosphorus has been applied to evaluate with high-level quantum mechanical/molecular mechanics (QM/MM) methods the reaction path of a phosphoryl transfer in the controversial beta-phosphoglucomutase enzyme. Our calculations show that a pentacoordinated intermediate is not stable in this enzyme. This indicates that the X-ray structure of a complex of the enzyme with a potential phosphorane was wrongly characterized. Enzyme dynamics have been studied in the context of the amino acid kinase family of enzymes. We have analysed the large-amplitude motions associated to ligand binding process involved in catalysis and allosteric regulation of the activity. By means of elastic network models, we show that the shared fold of this family involves shared dynamical features associated to ligand binding events. We have also analysed how oligomerization modulates large-amplitude motions and determines the binding mechanism. Another important aspect of enzymes is their adaptation to specific temperatures. We have analysed the relationship between thermostability and dynamics for a thermo-mesophilic pair of enzymes that was studied by means of neutron scattering. In this experiment, the flexibility of a thermophilic enzyme was found to be less sensitive to temperature changes than its mesophilic homologue pointing to a novel mechanism of protein thermostability. To understand the origin of these results, we performed molecular dynamics simulations to describe intramolecular motions and Brownian dynamics (with a box of 1000 protein molecules) to account for crowding effects in solution. Our results show that the different thermal behavior of the two proteins arises from the different diffusional properties of the two enzymes, despite being similar in size and shape. This is due to the fact that the thermophilic enzyme exhibits a more intense electrostatic potential thus introducing differences in the inter-protein electrostatic interactions in the crowded solution that, of course, affect diffusion. This provides a new interpretation of the results obtained in the original experiment. / La presente tesis se centra en la modelización molecular de tres aspectos necesarios para la función enzimática: reactividad, dinámica y termostabilidad. Los estudios de reactividad se han centrado en reacciones de transferencia de fosfato, las cuales están implicadas en un amplio rango de procesos biológicos. Se han estudiado los potentiales intermedios pentacoordinados (fosforanos) que pueden formarse en sistemas modelo y se observa que son especies muy polarizables. Los campos eléctricos externos pueden alterar su geometría y estabilidad de forma que pueden llegar a alterar el mecanismo de reacción. Con este conocimiento previo se ha estudiado con métodos QM/MM el controvertido intermedio pentacoordinado del enzima beta-fosfoglucomutasa. Los cálculos confirman que dicha especie no es un fosforano estable y que, por lo tanto, la estructura cristalográfica no fue resuelta correctamente en concordancia con recientes pruebas experimentales. El estudio de la dinámica se ha focalizado principalmente en los movimientos lentos de gran amplitud que están asociados a procesos de unión de sustrato y regulación de la actividad por alosterismo. Esta parte se ha centrado en la familia de las quinasas de aminoácido que presentan importantes cambios conformacionales asociados a su función biológica y que han sido muy bien caracterizadas por cristalografía. Mediante modelos de red elástica, se ha confirmado que la similitud estructural de los miembros de esta familia conlleva también similitud en la dinàmica de gran amplitud, la cual depende principalmente del plegamiento proteico. Además se han estudiado los efectos de oligomerización en la dinàmica de los miembros de esta familia. En tercer lugar, se ha analizado la relación entre termostabilidad y dinámica en el contexto de un experimento de dispersión de neutrones. Las simulaciones de dinámica molecular, para estudiar la flexibilidad interna, y de dinámica Browniana, en una caja de 1000 proteinas en disolución para tener en cuenta la difusión en “crowding”, muestran que el diferente comportamiento térmico de la movilidad que se observa en el experimento no se debe a la flexibilidad interna, sino a la distinta difusión que presentan el enzima termófilo y su homólogo mesófilo por sus diferentes interacciones electrostáticas en la superficie.

The role of heterogeneous catalysts in modern society is immense. The majority of catalysts are nanostructured solely in order to increase the fraction of atoms on their surface. The nanostructuring, however, introduces important changes in properties of the catalysts. Since commercial heterogeneous catalysts have a very complex hierarchical structure many academic studies are performed on so-called model catalysts. The latter are simplified systems that have a realistic degree of nanostructuring, but lack complexity on micrometer and millimeter scales. This thesis summarizes results of computational investigations of different ways how nanostructuring may affect properties and activity of model heterogeneous catalysts. Among various forms of model catalysts this thesis considers supported and unsupported transition metal nanoparticles, steps on surfaces and nanometer thick films. In all cases computational models were designed to be as similar as possible to respective experimental systems. In particular, the simulated nanoparticles were sufficiently big to be scalable with size. That is, their properties can be safely extrapolated to respective properties of much bigger nanoparticles present in the majority of experiments and applications. Since these models often contain hundreds of atoms they were investigated with density functional theory methods that yield a good compromise between accuracy and computational cost for systems of this size. In particular, the following studies were performed: •Adsorption and infrared spectroscopy properties of CHxOy (x=1-3, y=0-1) species on Pd nanoparticles were characterized. •The activity of edges Pd nanoparticles in methane dissociation was critically analyzed compared to that of Pd(111). •The activity of {111} terraces of Pd, Pt, Ni, and Rh nanoparticles in ethyl hydrogenation was compared to the activity of respective (111) single crystal surfaces. •A new method to optimize chemical ordering in bimetallic nanoparticles was proposed and applied to catalytically active PdAu, PdAg, PdCu and PdZn alloy particles. •The effect of MgO(100) support on physical and adsorptive properties of Pd and Pt nanoparticles was quantified. •H absorption into Pd and Pt nanoparticles supported on MgO(100) was simulated. •Atomic and electronic structure of steps on CeO2(111) was determined. •Two novel methods to calculate specific energy of steps on a surface were proposed and applied to steps on CeO2(111) •The ability of steps on CeO2(111) to form O vacancies was investigated using a newly proposed prescreening procedure. •Structure of ~1 nm thick Ce2O3 films was investigated by means of the simulated mechanical annealing method. •Reconstructrion of PdZn films on Pd(111) for monolayer thick films or under CO atmosphere was characterized. This diverse list of studies fulfills the goal of exploring various effects of different forms of nanostructuring on heterogeneous catalysts. Many of these studies are one-of- a-kind investigations describing certain effects induced by the nanostructuring on catalytically active materials for the first time. Another part of these studies describe novel simulation and analysis techniques that advance the methodology of computational investigations of nanostructured solid state systems. / La catálisis heterogénea juega un gran papel en el mundo. El material activo de un catalizador normalmente se dispersa en forma de nanopartículas. En ciertos casos se ha demostrado que la nanoestructura altera completamente las propiedades catalíticas del material. El objetivo principal de esta tesis es investigar cómo varias formas de nanoestructuración pueden alterar los materiales usados en catálisis heterogénea, a través de cálculos DFT. Los resultados de esta tesis incluyen: 1. Los filos de nanopartículas de Pd adsorben ciertas especies CHxOy significativamente más fuertamente que las caras {111} de las nanopartículas. 2. Los cálculos muestran que nanopartículas de Pd son catalíticamente más activas en la descomposición de metano que las superficies de Pd(111). 3. Las caras {111} de nanopartículas de Pd presentan una actividad catalítica mucho mayor en procesos de hidrogenación comparando con monocristales de Pd(111), siempre y cuando el sistema presenta H absorbido. 4. La aplicación de los Hamiltonianos topológicos propuestos en este trabajo a nanoparticulas de aleaciones bimetálicas permite optimizar su estructura en base a los resultados de cálculos de estructura electrónica. 5. El efecto de la superficie de MgO(100) en las propiedades físicas y adsorbentes de nanopartículas de Pd127 y Pt127 de 1.6 nm de tamaño depositadas puede ser insignificante. 6. La saturación de la superficie de las nanopartículas Pd127 y Pt127 con átomos de H afecta a su estructura geométrica y electrónica y a sus propiedades adsorbentes mucho más que la presencia del soporte de MgO(100). 7. Nanoislas formadas sobre la superficie de CeO2(111) exponen escalones con una estructura electrónica modificada y una mayor reducibilidad. 8. Los métodos (aquí propuestos) para calcular las energías absolutas de los escalones proporcionan una exactitud estadística superior al método preexistente a pesar del menor número de cálculos necesarios. 9. La estructura de las capas de Ce2O3 depende del substrato en el que crecen. 10. La estructura distorsionada (“zigzag”) de capas de PdZn sobre Pd(111) es más estable que la estructura convencional para monocapas y para capas cubiertas por moléculas de CO.

Iso-chloropropane dehydrohalogenation processes by alkali ion collisions (Li, Na and K) have been studied from a theoretical and an experimental point of view. Both methods have detected the following channels:(1): C(3)H(7)Cl + M(8)→ [C(3)H(6)M](+) + HCl; (2): C(3)H(7)Cl + M(+)→ C(3)H(6) + [HClM(]+); (3) :C(3)H(7)Cl + M(+)→ C(3)H(7) + MCl(+), where M represents the alkali ion. The first two reactions are dehydrohalogenations while the third one is a C-Cl bond heterolytic dissociation producing the alkali metal halide and C3H7+. Their reaction dynamics has been studied experimentally by molecular beam techniques while the theoretical research was carried out mainly by an exploration of potential energy surface (PES), a statistic study using direct dynamics as well as a RRKM analysis over the characterized PES. EXPERIMENTAL PART The described processes were studied using an octupolar radiofrequency-guided ion beam apparatus (RF-GIB) built in our lab. The alkali ions and iso-chloropropane in gas phase collide inside of octupolar reaction chamber at low pressures conditions where the reaction products are guided by a set of einzels lenses toward a mass spectrometer identifying the produced fragments. The obtention of the reactive cross section dependence as a function of collision energy for each channel and ion is the objective of this procedure. THEORETICAL PART The characterization of the PES, quasiclassical dynamics and RRKM study for the three alkali ions were performed in the theoretical part. The PES exploration and the possible reaction mechanisms was calculated by quantum chemistry using GAMESS 2008 package at MP2 level. The dynamics simulation was performed by Venus/NWChem, running on the fly classical trajectories. This software solves the classical equations of motion using the potential energy obtained from chemistry calculations, with the aim to calculate reactive cross sections. The visualization of pathways and a vibro-rotational analysis complete the dynamics study. Finally, the RRKM study allows to obtain a Kinetic Monte Carlo simulation. This model gives information about the several steps of the whole mechanism of the system and it complements the provided data by experimentation and the “on the fly” dynamics. / S’han estudiat les reaccions de deshidrohalogenació del compost iso-cloropropà induïdes per col•lisió d’ions alcalins (Li, Na i K, representats per M) tant des d’un punt de vista teòric com experimental. Els canals detectats per ambdues vies són: :(1): C(3)H(7)Cl + M(8)→ [C(3)H(6)M](+) + HCl; (2): C(3)H(7)Cl + M(+)→ C(3)H(6) + [HClM](+); (3) :C(3)H(7)Cl + M(+)→ C(3)H(7) + MCl(+), En les dues primeres reaccions té lloc la pròpiament dita deshidrohalogenació i, en canvi, en el tercer cas es tracta d'una dissociació heterolítica de l’enllaç C-Cl amb la formació de l’halur del metall alcalí i del catió C(3)H(7)(+). A la part experimental s’ha realitzat un estudi de dinàmica de reacció mitjançant la tècnica dels feixos moleculars mentre que la part teòrica ha inclòs l’exploració de la superfície d’energia potencial (SEP) del procés, un estudi estadístic per dinàmica directa i un anàlisi RRKM sobre la SEP caracteritzada. Tanmateix, es comparen els citats resultats obtinguts experimentalment amb els del tractament teòric amb la finalitat d’establir validesa i grau de complementació entre ambdós procediments. A més, les simulacions teòriques permeten determinar els diferents mecanismes duts a terme per cada procés i la caracterització del camí de reacció sobre la SEP calculada. PART EXPERIMENTAL Experimentalment s’ha dut a terme l’estudi dels citats processos de deshidrohalogenació fent servir un aparell de feixos iònics guiats per radiofreqüència (Radiofrequency-guided ion beam, RF-GIB) octupolar construït al nostre laboratori. En aquest aparell els ions alcalins focalitzats per una sèrie de lents Einzel i guiats per un camp de radiofreqüència col•lisionen contra la mostra d’iso-cloropropà en fase gas allotjada a la cambra de reacció de l’octupol a baixa pressió. Un altre conjunt de lents d’einzels dirigeixen els productes cap a un espectròmetre de masses encarregat d’identificar-los en funció de la seva massa. L'objectiu experimental és caracteritzar la dependència de les seccions eficaces reactives en funció de l’energia de col•lisió per a cada canal de reacció i per els tres ions alcalins estudiats. PART TEÒRICA La part teòrica consta de la caracterització de la SEP dels processos, de la corresponent dinàmica clàssica “on the fly” i de l’estudi RRKM per a cadascun dels tres ions alcalins. L’exploració de la SEP ha estat realitzada mitjançant càlculs ab initio utilitzant el programa de química quàntica GAMESS 2008 sota el mètode post Hartree-Fock a nivell de teoria de pertorbacions de segon ordre MP2. Amb aquest procediment s’ha caracteritzat la topologia de les diferents SEP, així com els seus possibles mecanismes de reacció els quals han permès justificar els resultats obtinguts experimentalment. La dinàmica “on the fly” utilitza el software Venus/NWChem el qual simula la reacció de deshidrohalogenació estudiada experimentalment mitjançant trajectòries clàssiques. Aquest software simula la col•lisió per medi de la mecànica newtoniana (Venus) obtenint l’energia potencial d’interacció per mètodes de química quàntica (NWChem) a cada pas d’integració i fent servir DFT. Mitjançant aquest procediment es simula un nombre suficientment gran de trajectòries amb l'objectiu de confeccionar una estadística fiable, calcular reactivitats i seccions eficaces reactives per a ser comparades amb els resultats experimentals, així com la visualització del camí de reacció pres a cada canal i per a cadascun dels tres ions alcalins. Finalment, l’obtenció de constants de velocitat per mitjà d’un estudi RRKM condueix a realitzar una simulació pel mètode Kinetic Monte Carlo. Aquest estudi proporciona informació sobre l’evolució del sistema entre les diverses etapes del mecanisme global fins assolir condicions estacionaries i complementa la informació proporcionada per l’experimentació i la dinàmica “on the fly”.

It is well established that organic radical-anions, such as reduced tetracyanoethylene (i.e., [TCNE]•(-)), may form dianionic dimers exhibiting long, multicenter bonding. This bond arises from the overlap of the b(2g) SOMOs of [TCNE]•- to form a doubly-occupied bonding and an empty antibonding combination of orbitals of b2u and b1g symmetry, respectively, leading to a diamagnetic pi-[TCNE](2(2-)) dimer. Long, multicenter bonds were first experimentally and theoretically characterized in crystals of [TCNE]•- salts, whose dimers exhibit an intermonomer distance of ~2.9 Å, and they were found to present the same electronic properties as conventional covalent bonds. Further studies in dichloromethane solution at low temperature determined its equilibrium constant KD and enthalpy and entropy of dimerization (delta-HD and delta-SD) by UV-vis and EPR measurements. Since their first characterization several other organic radicals have been shown to exhibit long, multicenter bonding; among them, other radicalanions such as tetracyanobenzene (TCNB) or tetracyanopyrazine (TCNP), radical-cations such as tetrathiafulvalene (TTF), or neutral radicals such as phenalenyl derivatives. Salts of the aforementioned organic radical-ions are well known to exhibit technologically important properties such as magnetic ordering, metal-like electrical conductivity, and even superconductivity. TCNE, TCNQ, and TCNP, to list a few examples, are building blocks in molecule-based bulk ferromagnets having magnetic ordering temperatures above room temperature. However, the electron pairing resulting from the formation of long, multicenter dimers would impede these physical properties. Moreover, recent experimental and theoretical work showed the presence of long, multicenter bonded pi-[TTF](2(2+)) dimers in supramolecular aggregates at room temperature. These supramolecular aggregates were recently proposed as an emerging class of materials with potential ability on molecular switching applications. It is thus of high importance to achieve a complete understanding on the formation and nature of such interactions. The present thesis focuses in the computational study of long, multicenter bonding. The work is divided into two parts: a first part where the fundamentals of long, multicenter bonding are evaluated, and a second part where room-temperature long, multicenter bonding is studied. In the first part, an extensive characterization with a wide variety of density functionals and active spaces is performed in the gas phase, for the pi-[TCNE](2(2-)), pi-[TTF](2(2+)), pi-[TCNB](2(2-)), and pi-[TCNP](2(2-)) dimers. Moreover, a comprehensive study of the pi-[TCNE](2(2-)) dimer in explicit dichloromethane solution is performed by means of molecular dynamics. Finally, the last two articles focus in solid state long, multicenter bonded dimers. The relative orientation of the pi-[TCNB] (2(2-)) and pi-[TCNP]2(2(2-)) dimers is challenged in the former, while a thorough characterization of the four polymorphs of the [TTF][TCNE] charge-transfer crystal is done in the latter. In the latter, the two established kinds of pi-[TCNE](2(2-)) dimers, actually only found in the pi and pi- polymorphs of [TTF][TCNE], are revised. The second part of the thesis focuses in room-temperature long, multicenter bonding. There are two categories where long, multicenter bonding is still preserved at room temperature: oligomeric donors or acceptors and supramolecular aggregations. In this thesis, some examples of both categories of room-temperature long, multicenter bonding are analyzed. The dimerization of oxidized alpha, beta-substituted heptathienoacene, [D4T7]•+ is investigated, as well as the effect of adding bulky substituents. Furthermore, the room-temperature formation of pi- [TTF] (2(2+)) involving its inclusion in the cavity of a CB[8], and as a building block of a molecular clip and a [3]catenane is also carefully studied. It is quantitatively shown in the thesis that the extra stability, which permits the room-temperature observation of long, multicenter bonding, is due to an increase of dispersion interactions while a decrease of the internal repulsion between the radical-ions. / La següent tesi s’emmarca dins l’estudi dels enllaços multicentre a llarga distància entre radicals orgànics. Aquests enllaços varen ser observats per primer cop a finals dels anys 60, però no fou fins al 2001 quan, a través d’un estudi teòric-experimental, es caracteritzaren. Els enllaços multicentre a llarga distància s’originen entre radicals orgànics a distàncies força majors que els enllaços covalents, però inferiors a distàncies de van der Waals (típicament, el dímer pi[TCNE](2)(2-) té una distància d’equilibri de 2.89 Å). En la seva distància d’equilibri, els orbitals SOMO dels radicals se solapen i combinen formant una combinació enllaçant doblement ocupada (l’HOMO) i una combinació antienllaçant desocupada (el LUMO), resultant-ne un dímer diamagnètic. El treball realitzat en aquesta tesi es divideix en dues parts, l’estudi fonamental dels enllaços multicentre a llarga distància i l’estudi d’aquest fenomen a temperatura ambient. En la primera part, es realitza un extens estudi metodològic de quatre dímers que presenten aquest tipus d’enllaç, pi-[TCNE] (2)(2)-, pi-[TCNB] (2)(2-), pi-TCNP] (2)(2-) i pi-[TTF] (2)(2+), pels quals es calibren diversos espais actius i fins a 23 funcionals de la densitat. A més a més, es realitza un estudi del dímer de pi-[TCNE] (2)(2-) en fase condensada, on s’obtenen dades de la seva solvatació i del seu comportament a diferents temperatures. També es fa un estudi en estat sòlid dels dímers pi-[TCNB] (2)(2-) i pi-[TCNP] (2)(2-), on es compara la naturalesa de la seva interacció en fase gas i estat sòlid i s’estudia la seva orientació relativa. Finalment s’han estudiat les quatre formes polimòrfiques del cristall de [TTF][TCNE], on s’ha caracteritzat l’enllaç a llarga distància entre pi-[TTF•••TCNE]. En la segona part, certs exemples de les dues famílies de compostos que exhibeixen enllaços multicentre a llarga distància a temperatura ambient han estat estudiades. Aquestes dues famílies són els oligòmers de donadors o acceptors i els agregats supramoleculars. Un oligòmer de tiofè, l’oligotienoacè (anells de tiofè fusionats) de set membres, ha estat estudiat. S’ha avaluat l’impacte de substituents laterals, així com l’efecte de la solvatació i de tenir un excés de contraions en la dissolució. De la segona família de compostos s’ha estudiat la inclusió d’un dímer pi-[TTF] (2)(2+) dins la cavitat d’un macrocicle cucurbit[8]uril, així com la dimerització de clips moleculars que contenen TTF i un compost mecànicament entrellaçat [3]catenan el qual conté TTF en els macrocicles exteriors.

In this thesis, several physico-chemical phenomena occurring at the two-dimensional environment of a Langmuir monolayer are studied. In the first section, the characterization of Langmuir monolayers of an azobenzene derivative is presented, together with the induction of chirality by the action of a chemical and a physical force, inside labile condensed domains formed by the trans isomer. This has been compared with results of another study done in the group for a homologue azobenzene molecule. In addition, we have studied a heterochiral recognition phenomenon in monolayers by means of the interaction of two enantiomeric chiral azobenzene derivative surfactants. The following section focuses on the field of two-dimensional microfluidics, and encompasses the analysis of different transport processes occurring at the interface between two monolayers that are coflowing through a channel. In this context, studies of the diffusion between co-flowing monolayers have resulted in a slight increase in the diffusion coefficient value for experiments with curvilinear channels, and when vortices are introduced in the system. In contrast, increasing the concentration gradient between co-flowing monolayers has not been successful at producing a noticeable impact in the measured diffusion coefficient values. On the other hand, a two-dimensional dissolution process has been visualized, with a rate that follows a classic dissolution model. Different unsuccessful attempts to realize a chemical reaction between coflowing monolayers are presented. Moreover, we have addressed the flow of monolayers in open microchannels driven by surface tension gradients, determining that drag at the interface and lateral confinement result in the formation of backflow patterns that carry the subphase liquid upstream through self-organized micro-ducts. This backflow patterns depend on channel geometry and are bound by velocity stagnation surfaces, whose shape and location has been related to the interfacial velocity profiles by means of the combination of a simple model and particle image velocimetry measurements. In the last section, we adapt the protocols used in two-dimensional microfluidics to study the insertion and diffusion of a protein in a phospholipid monolayer. / En aquesta tesi s’han estudiat diferents fenòmens físico-químics en l’àmbit de les monocapes de Langmuir. En una primera secció, s’han caracteritzat monocapes de Langmuir d’un derivat d’azobenzè que presenta una separació de fases entre els seus dos possibles isòmers. S’ha explorat la inducció de quiralitat en dominis condensats aïllats, rics en isòmer trans, mitjançant l’acció d’una força quiral química (un dopant quiral), i una de física (un vòrtex). Els resultats obtinguts s’han comparat amb els d’un altre estudi realitzat prèviament en el grup, fet amb un derivat d’azobenzè homòleg. A part, s’ha estudiat un fenomen de reconeixement quiral en monocapes, degut a la interacció de dos enantiòmers quirals d’un altre derivat azobenzènic. Una segona secció de la tesi es centra en el camp de la microfluídica bidimensional, i mostra l’estudi de diferents fenòmens de transport que ocorren en la interfase entre dues monocapes que flueixen al llarg d’un canal. En concret, s’han fet experiments de difusió entre monocapes que co-flueixen per un canal, per tal de trobar les condicions en les que s’obté un increment de la difusió, traduït en un augment del valor del coeficient de difusió mesurat. D’aquesta manera, els experiments realitzats en circuits amb forma de serpentí, o en els que s’hi ha creat vòrtexs, presenten un augment en la difusió. En canvi, l’efecte de l’augment del gradient de concentració existent entre les dues monocapes no ha resultat en canvis apreciables en els coeficients de difusió mesurats. D’altra banda, s’ha visualitzat un procés de dissolució en dues dimensions que segueix el model de dissolució clàssic, i s’han fet experiments per tal d’aconseguir visualitzar una reacció en la línia de contacte entre dues monocapes. A més, s’ha estudiat la formació d’un flux de retorn en la subfase com a resultat del flux d’una monocapa en la interfase, i s’ha pogut relacionar amb perfils de velocitat interficials anòmals obtinguts. En l’última secció, s’han adaptat els protocols experimentals utilitzats en la microfluídica bidimensional, per tal d’estudiar la inserció i difusió d’una proteïna en una monocapa de fosfolípids.

Tesi realitzada a l'Institut de Bioenginyeria de Catalunya (IBEC) / Las interacciones proteína-proteína son determinantes para las funciones biológicas y constituyen dianas terapéuticas de gran interés. Muchas de ellas son mediadas por péptidos cortos donde una secuencia lineal adopta una estructura helicoidal. Moléculas que imitan esos péptidos se han usado con éxito como inhibidores de las interacciones en que participan. La posibilidad de usar versiones de esos péptidos diseñadas para poder controlar con luz su estructura y actividad inhibidora abre nuevas vías para la investigación de los procesos biológicos a escala molecular y la intervención terapéutica en los mismos. En esta tesis se desarrolla un panel de péptidos de estructura fotoconmutable mediante acoplamiento de azobenceno a su estructura. Estos péptidos derivan de la parte de la proteína β-arrestina que interacciona con β-adaptina 2 y tienen como objetivo la inhibición fotocontrolada de esa interacción. Se estudian los factores de diseño molecular que arrojan mejores resultados de fotontrol de la estructura y la actividad inhibidora, incluyendo diferentes posiciones y distancias de acoplamiento de azobenceno y uso de aminoácidos no naturales en la secuencia peptídica. Asimismo, se aplican algunos de los péptidos desarrollados al fotocontrol en células vivas del proceso de endocitosis mediada por clatrina, un proceso de importancia cardinal en la biología celular de los organimos eucariotas, logrando una alteración del mismo dependiente de la iluminación. En conjunto, estos trabajos suponen una demostración de aplicabilidad de la imitación directa de estructuras biológicas en el diseño de moléculas fotocontroladas para el control de las interacciones y actividades biológicas de las estructuras imitadas. Los principios de diseño empleados son potencialmente aplicables a otras interacciones proteicas intracelulares de gran relevancia biológica y clínica. / Protein-protein interactions are crucial for biological functions and constitute therapeutic targets of great interest. Many protein-protein interactions are mediated by short peptides in which a linear sequence adopts a helical structure. Molecules that mimic these peptides have been successfully used as inhibitors of the interactions in which they are involved. The possibility of using versions of such peptides modified by design in order to control their structure and inhibitory activity by optical means opens new avenues for the investigation of biological processes at the molecular level and therapeutic intervention in their disorders. In this thesis a panel of peptides with photoswitchable secondary structure is developed by cross-coupling azobenzene to selected pairs of cysteine lateral chains introduced in their sequences. These peptides are derived from the C-terminal region of the protein β-arrestin, known to interact with β-adaptin 2. Furthermore, a peptide termed BAP-long corresponding to that region is known to bind β-adaptin 2 as well as to adopt a helical conformation when bound to it while remaining unstructured when free. 20-mer BAP-long is an appealing candidate for photocontrol of secondary structure with potential for the photocontrol of binding affinity and of biological activity related to the interaction of β-arrestin with β-adaptin 2 in living cells. The first part of the thesis introduces the work and reviews literature on chemical photoswitches as well as their application to biomolecules and to molecular mechanisms of biological functions. Different photoswitches are presented and different approaches to the control of biomolecules are discussed separating pharmacological applications from applications requiring genetic modification (optogenetics). The focus is on the photocontrol of secondary structure of biomolecules, particularly peptides and proteins, as a strategy to achieve photocontrol of their functions. A final sub-section introduces the system in which the assays presented have taken place: clathrin-mediated endocytosis of membrane receptors. The second part of the thesis investigates molecular design factors that yield superior results in terms of fotocontrol of structure and inhibitory activity of versions of BAP-long. These features include different coupling positions and distances of the azobenzene photoswitch along the peptide structure as well as use of unnatural amino acids in the peptide sequence. In this part of the thesis the hypothesis that photocontrol of peptide structure results in photocontrol of affinity and ability to competitively inhibit the interaction of β-arrestin with β-adaptin is verified in vitro. Furthermore, the observation is made that for this particular system and potentially for others of similar characteristics the better photoswitchable inhibitors of the interaction are the least structured peptides when free in solution. In the third part of the thesis some of the peptides are applied in living cells to photocontrol clathrin-mediated endocytosis, a process of cardinal importance in eukaryotic organisms and in which the interaction of β-arrestin with β-adaptin plays an important role. Photocontrolled alteration of endocytosis of the transferrin receptor is achieved with the same light dependence observed in the previous section for binding. This is in agreement with the second hypothesis that photocontrol of affinity results in photocontrol of the biological activity associated to the interaction, probably by competition of the photoswitchable peptides against the natural proteins for the available binding sites. The results also indicate an ability of the peptides to cross cell membranes confirmed by tracking of fluorescent peptides. Photocontrolled alteration of clathrin-containing structures is also observed. Together, these studies represent a demonstration of the applicability of the direct imitation of biomolecules in designing photoswitchable inhibitors to control the interaction and biological activities of the mimicked structures. The design principles used are potentially applicable to other intracellular protein-protein interactions of biological and clinical relevance.

Throughout this thesis, we have studied ZnO and its properties in a bottom-up manner through a dimensionality range starting from 0D nanoparticles to 3D bulk phases. For the 0D clusters and the 2D nanofilms studied we also considered the effect of a support in models designed to study ZnO thin film growth on the Ag(111) surface. In chapter 3, we have studied ZnO nanoclusters on a Ag support and compared their properties with free space ZnO nanoclusters. In this chapter we highlighted the importance of the presence of the support during the global optimization of the clusters (i.e. as opposed to global optimization of the clusters in free space and then introducing a support). Our results show that the presence of the support strongly affects the energetic stability ranking of the nanocluster isomers. More drastically, after a certain cluster size, the support also stabilizes selectively 2D type structures, which are not stable in free space, with respect to the 3D clusters. The extra stabilization of supported 2D clusters is attributed mainly to the contact area, which is evidently greater for 2D clusters where all the atoms can interact with the surface. The importance of the contact are is also observed for 3D clusters, as ellipsoid bubbles or inflated double layer clusters being of lower energy than more spherical clusters on the support whereas the latter, more symmetric 3D clusters are more stable in free space. Matching of the cluster structure with the surface morphology was found to be another factor determining cluster stability. The Zn3O3 sixmembered ring, which is one of the main motifs for both 3D and 2D clusters, matches best with the Ag(111) surface because it follows the same six-fold (C6) symmetry (or its trigonal C3 subgroup with a three-fold axis, taking into account the distinction between Zn and O atoms). However because of the lattice size differences, such matching dies away for larger ZnO clusters. The preferential stabilities of the 2D structures of ZnO clusters can be seen as the initial stages of thin film growth and is found to be in line with the experimentally observed layered ZnO sheets on the Ag(111) surface. In Chapter 4, we have considered a full 2D-ZnO sheet on Ag(111) surface and also investigated also how H atoms interact with it. Following our results for ZnO nanoclusters on the Ag surface, we highlighted the importance of the degree of 2D-ZnO:Ag(111) unit cell commensurability for calculating accurate sheeton-substrate binding energies. We have found a 8:9 commensurate monolayer to be more favored with interatomic potentials and a 7:8 commensurate monolayer with DFT calculations, where the latter is found in experiment. Our calculations showed no evidence of charge transfer or covalent bonding between the Ag(111) surface and the 2D-ZnO sheet, but did show that the ZnO sheet and the Ag(111) surface exhibit small structural distortions in order to maximize their mutual interaction. Calculations of the unsupported 2D-ZnO sheet interacting with hydrogen provided strong evidence for H forming a low energy Zn 4s–H 1s multi center bonding state when passing through a Zn3O3ring of the 2D-ZnO sheet, thus allowing for relatively facile H transport through the sheet. In chapter 5, we have extended our study of supported 2D ZnO nanofilms with higher coverage models, including triangular islands on top of two full monolayers, prepared to model the experimental system. Our results showed that the triangular adlayer islands induce a transition to the WZ structure in the island core and in local region in the two layers immediately below the island core. The islands are also found to have BCT-structured reconstructions on their edges and T1-structured reconstructions on their corners. These models are found to better match the experimental structural data for the experimental 2.7 ML Ag-supported ZnO film with respect to models assuming a purely layered or a purely WZ structure. In chapter 6, we focused on 4ML nanofilms and compared bulk and the 4 ML nanofilm poymorphism of ZnO. Our results revealed that the stability range of nanofilms and their energetic ordering are radically different than that of bulk polymorphs. We have developed a method to generate a wide range of new low energy nanofilm and bulk polymorphs using nets as a basis, and showed that there exist at least three nanofilm structures with trigonal basal plane symmetry compatible epitaxial growth on fcc metal (111) surfaces that are more stable than layered-ZnO. While confirming the previous theoretical studies predicting the BCT-ZnO phase as being the lowest energy free-standing nanofim for small thicknesses, we obtained a range of structurally related and near energetically degenerate phases, indicating there exists BCT polytypism. With increasing thickness we found that atomically reconstructed wz-ZnO becomes more stable than BCT-ZnO for ~14 MLs, and is always more stable than non-reconstructed wz-ZnO. We have also stressed the influence of strain on polymorphism by showing that BCT-ZnO and layered-ZnO nanofilms are unstable to novel polymorphs under in-plane strain. Together with the T1 structures and BCT structures which were also predicted as reconstructions on island corners in the previous chapter, our results strongly suggest that many new nanofilm polymorphs should be experimentally accessible, and in some cases, may have even already been observed. In chapter 7, we focused on bulk polymorphism and, specifically, investigated the effect of nanoporosity. Our results showed that both energetic instability and band gap increase with nanoporosity and we predicted that nanoporosity could induce band gap increases of up to ~1.5 eV relative to wurtzite ZnO. We showed that the band gap increase is related with bandwidth changes in the conduction band and the valance band. We suggested that the underlying physical mechanism for this effect is that introducing nanoporosity, and thus periodic internal void space, restricts extended orbital overlaps and thus decreases bandwidths. Due to the generality of this argument, we expect that nanoporosity could similarly affect bandgap values in a wide range of materials and could be employed as a band gap engineering method. / El treball de recerca desenvolupat en aquesta tesi es centra en ZnO, un dels semiconductors de tipus II-VI amb un ampli ventall d’aplicacions. En les estructures (ZnO)n suportades, s’observa que la presència del suport afecta l’ordre d’estabilitats dels mateixos però de manera molt més dràstica afecta selectivament les estructures bidimensionals (2D) que, a partir d’una certa grandària, en fase gas són menys estables que les tridimensionals (3D). Els càlculs per a la làmina 2D-ZnO aïllada interaccionant amb l’hidrogen proporcionen una forta evidència per a la formació d’un estat d’enllaços multi-centres de baixa energia quan passa a través de l’anell de Zn3O3 de la làmina 2D-ZnO, permetent així de forma relativament fàcil el transport d’hidrogen a través de la làmina. Quan canviem a models amb illes mes grans, observem reconstruccions estructurals a l’interior i sota l’illa formada per una nova capa incompleta. L’interior de les illes triangulars adopta estructura WZ i esta rodejada per vores amb estructures BCT i cantonades amb estructura T1. S’ha observat que aquests models presenten en un millor acord estructural amb les dades experimentals per el cas de les lamines formades per 2.7 ML que no pas respecte als models que assumeixen una estructura purament grafítica o purament WZ. Hem generat un ampli rang de polimorfs de ZnO basats en lamines hexagonals inspirades en l’enumeració de les seves xarxes subjacents característiques i evaluant l’estabilitat del sòlid “bulk” i les nano-lamines d’aquestes estructures mitjançant calculs ab initio. Hem observat un ampli polimorfisme d’estructures de baixa energia en les nano-lamines amb un ordre d’estabilitat totalment diferent al del sòlid “bulk”. A partir d’aquestes bases generals hem pogut tenir un millor coneixement de les transicions estructurals observades durant el creixement epitaxial i les prediccions d’estabilitat de les nano-lamines en variar-ne el gruix i la pressió exercida. Hem conclòs els nostres resultats explicant que la nanoporositat està inextricablement connectada tant amb la Erel com amb el ΔEgap i hem predit que la nanoporositat pot induir un increment en el band gap de fins a ~1.5 eV relatius a la wurtzita ZnO. Comprovant també la generalitat d’aquest fenomen, pe’l CdS i pel CdSe suggerim que la nanoporositat pot ser emprada com un mètode genèric d’enginyeria de band gap per materials funcionals morfològicament i electrònicament.

Els rotors, motors i engranatges moleculars són molècules o sistemes moleculars que tenen com a característica que presenten moviments conformacionals de gran amplitud, majoritàriament associats a rotacions internes al voltant d’un o diversos enllaços senzills entre els seus àtoms. Aquesta propietat permet a aquestes molècules adoptar diferents geometries conformacionals en funció de la rotació al voltant d’aquests enllaços, podent donar comportaments mecànics anàlogs al dʼengranatges macroscòpics, de manera que aquestes molècules puguin ser considerades com a components bàsics per a un futur disseny de màquines nanoscòpiques més complexes. És per aquesta raó que l'anàlisi del comportament dinàmic de rotors i engranatges moleculars ha despertat l’interès d’una gran quantitat de científics que, des de fa temps, treballen en la síntesi i caracterització d’aquest tipus de compostos. Una manera de poder abordar l’estudi teòric dels rotors moleculars sense haver de renunciar a l’ús d’un mètode de càlcul de les interaccions intermoleculars acurat, és efectuant una dinàmica molecular restringida, on només es tenen en compte un nombre reduït de graus de llibertat mentre que els efectes de la resta modes en el comportament dinàmic es menysprea o s’inclou només de manera aproximada com a pertorbació del moviment que s’estudia en detall. D’aquesta manera és possible reduir el cost computacional del càlcul i poder accedir així, a temps de simulació molt més elevats amb un cost computacional assumible. En aquesta tesi doctoral s’ha desenvolupat un conjunt de programes informàtics que permeten simular el comportament dinàmic de sistemes formats per un nombre de fragments que es consideren rígids amb una energia potencial total definida a partir d’interaccions a parells entre ells. Això permet tractar sistemes grans reduint el nombre de graus de llibertat, separant així les interaccions més rellevants. D’aquesta manera, al tenir en compte només uns pocs graus de llibertat, es pot realitzar un càlcul més precís de l’energia en un temps assumible. Per tal de descriure les interaccions entre fragments s’han calculat superfícies de potencial en funció de les variables que descriuen les rotacions internes entre fragments rígids. Aquesta descripció, permet veure més clarament els possibles acoblaments entre els diferents graus de llibertat rotacionals de la molècula. Per fer-ho, s’ha elaborat una metodologia que permet descriure els processos de flexió que tenen lloc a la molècula al mateix temps que és produeix la rotació. Amb aquesta metodologia, s’ha realitzat l’estudi dels tripticil[n]helicens, molècules formades per la unió d’un grup tripticil i un helicè mitjançant un enllaç senzill, que han estat estudiades per la seva relació amb els anomenats trinquets moleculars, sistemes on hi ha una rotació interna en un entorn asimètric degut a la presència de fragments moleculars quirals. Utilitzant programes de simulació de Monte Carlo i de dinàmica molecular desenvolupats en el transcurs de la tesi s’ha estudiat també en col•laboració amb el grup experimental del Prof. Miguel A. Garcia-Garibay de la Universitat de California, dos cristalls amfidinàmics, sòlids on fragments de les molècules empaquetades conserven una alta llibertat de rotació, sintetitzats recentment: el rotor de mestranol i l’IDipp-C60. / Molecular motors, rotors and gears are complex molecules that undergo wide conformational movements that mimic those of their macroscopic mechanical counterparts. For this reason these molecular systems have recently been the subject of numerous experimental and theoretical studies with the aim to incorporate them as basic building blocks of more complex nanoscopic devices. Due to their intrinsic structural complexity it is difficult to perform accurate dynamical studies using standard molecular dynamics techniques considering all atoms of the system and for this reason in this thesis we have developed programs to simulate the dynamical behavior of such systems !considering only a restricted set of degrees of freedom. The systems are modeled by a collection of rigid fragments that interact through pair potentials that lead to a reduced potential energy surface for the relevant degrees of freedom that is being used in conjunction of molecular dynamics or Monte Carlo simulation techniques to study the dynamic behavior of molecular gears or ensembles of molecular rotors. Using the general purpose molecular dynamics and Monte Carlo programs developed in this thesis have also been adapted to be used in the study of the dynamical behavior of amphidynamic solids, a new class of molecular crystals where some fragments of the constituent molecules exhibit large conformational motions. This part of the work, devoted to the simulation of the dynamic behavior of the mestranol rotor and the crystals of IDipp-C60 has been developed in collaboration with the experimental group of Prof. Miguel Angel García Garibay at UCLA that worked in the synthesis and experimental characterization of these two compounds.

Los sulfuros de metales de transición exhiben una amplia variedad de propiedades eléctricas y magnéticas que los hacen interesantes tanto en el ámbito científico como en el de las aplicaciones tecnológicas. En este trabajo se estudia, utilizando cálculos ab intio, la estructura electrónica y las propiedades de un conjunto de calcogenuros, la mayoría sulfuros de cobre complejos, para intentar relacionar su estructura electrónica con las propiedades de transporte electrónico y magnéticas. En el primer capítulo se presenta una metodología muy simple para asignar estados de oxidación de metales de transición en compuestos cristalinos que consiste en el análisis conjunto de las energías de los orbitales de core y la población de la capa d de valencia obtenidas en un cálculo de bandas. El método se ha aplicado con éxito a los sulfuros de cobre para los cuales es difícil establecer estados de oxidación de manera fiable a partir de datos experimentales y se ha extendido a compuestos de plata, en particular para elucidar los estados de oxidación de los metales en algunos óxidos mixtos de cobre y plata. Paralelamente se han estudiado también las propiedades magnéticas y electrónicas de CuFeS2 y CuS, dos sulfuros de cobre con propiedades eléctricas y magnéticas complejas para los que se encuentran ciertos datos contradictorios en la literatura. En particular, para la covelina, CuS, se han estudiado aspectos de su estructura electrónica con la finalidad de analizar si las interacciones débiles d10-d10 juegan un papel importante o no en la transición estructural que sufre este compuesto a baja temperatura y para CuFeS2 el trabajo se ha centrado en la determinación de las constantes de acoplamiento magnético para intentar explicar la curva compleja de susceptibilidad magnética que se encuentra para este compuesto. En la presente tesis también se incluye un estudio en el que se intenta predecir si los sulfuros cuaternarios laminares AFeCuS2 con estructura tipo ThCr2Si2 son capaces de soportar litio, tal como lo hacen los sulfuros cuaternarios con estructura CaAl2Si2. En este estudio también se explica porqué no es estable la estructura de tipo CaAl2Si2 cuando se elimina todo el litio de la fase laminar LiFeCuS2. Por último, se presenta un estudio de la estructura electrónica de los calcogenuros TaS3, NbSe3 y TaSe3. El compuesto NbSe3 es un conductor metálico para el cual hay cierta controversia en la literatura sobre si en su estructura de bandas hay cuatro o cinco bandas cruzando el nivel de Fermi. A raíz de un experimento reciente mediante la técnica ARPES en el que se muestra, sin lugar a dudas, que este compuesto presenta cuatro bandas que cruzan el nivel de Fermi hemos realizado un estudio pormenorizado de sus estructura electrónica junto a la de TaS, y TaSe3 en el que se pone de manifiesto que realmente solo hay cuatro bandas cruzando el nivel de Fermi pero que, debido a la importancia de las interacciones débiles Se•••Se que no se describen correctamente en la teoría del funcional de la densidad en algunos cálculos puede llegar a aparecer una quinta banda cruzando el nivel de Fermi. / In this thesis we have applied first principles electronic structure methods to study the electronic structure of several transition metal chalcogenides in order to establish the relation between their electronic structure and their electrical and magnetic properties. In the first chapter we develop a new strategy based on the simultaneous use of core orbital energies and valence d shell populations to establish oxidation states of transition metal atoms in complex solid state compounds. As a test case we have successfully applied this new method to copper sulfides and mixed copper-silver oxides. The second and third chapters are devoted to the study of the electronic structure of two copper sulphides, CuS and CuFeS2. For the first one, our analysis focuses on the role that weak d10•••d10 interactions may play in the structural phase transition exhibited by this compound, while for the latter our study deals with the evaluation of exchange coupling constants in order to understand its complex magnetic susceptibility curve. The thesis finishes with a chapter devoted to TaS3, NbSe3 y TaSe3, three pseudo 1D transition metal chalcogenides that have been extensively studied both from the theoretical and experimental points of views. Our main motivation has been the presentation of a recent ARPES study for NbSe3 where it is shown that there are only four bands crossing the Fermi level, a question that is unclear in the literature where in some cases the presence of a fifth band is suggested. Our study shows that indeed there are only four bands crossing the Fermi level, but that the weak Se•••Se interactions present in this structure, which are poorly described in DFT lead in some calculations to a fifth band crossing erroneously the Fermi level.

Los Salen [N, N'-bis(salicilideno)etilendiamina] son ligandos tetradentados lineales, sistemas N2O2-coordinados, que se obtienen de la reacción de condensación entre la diamina y los precursores(sustituidos)del salicilaldehído. Los complejos metálicos de salen combinan las ventajas típicas tales como la facilidad de la variación en las características estéricas y electrónicas, y el uso de estrategias modulares que permiten la manipulación de diferentes fragmentos de los sistemas de ligandos. Los complejos metálicos de salen son versátiles y han demostrado ser catalizadores eficaces para muchas conversiones asimétricas, incluyendo (ep)oxidaciones, reacciones de apertura de anillo de epóxidos y polimerizaciones estéreo-selectivas. Últimamente, los ligandos de salen con puentes de fenilo ("salphens" o "salophens", Esquema 1) y estructuras relacionadas, han empezado a llamar la atención debido a sus ventajas particulares con respecto a sus análogos de salen; estasestructuras representan sistemas de ligandos π-conjugados con propiedades fotofísicas ajustables, y son más rentables que los correspondientes ligandos de salen (quirales). Por estas razones, los sistemas salphen tienen un excelente potencial como pilares básicos en la ciencia de materiales, entre otras aplicaciones. Esquema 1. Representación esquemática de un ligando salphen que muestra el bolsillo de unión del metal N2O2y las diversas sustituciones posibles.También debe tenerse en cuenta que la geometría rígida alrededor del centro metálico, dictada por el ligando salphen, puede ser utilizada para manipular las propiedades tales como, el carácter ácido de Lewis del metal y por lo tanto se puede aplicar eficazmente para aumentar la reactividad del complejo resultante. Por lo tanto, el trabajo presentado en esta tesis se ha centrado en el estudio de propiedades de auto-ensamblaje y en el desarrollo de nuevas aplicaciones para los complejos de Zn(salphen).Los dos primeros capítulos (2 y 3) presentan estudios completos sobre el auto-ensamblaje de diferentes complejos de Zn(salphen) multinucleares, centrándose en el tipo y la intensidad de las interacciones involucradas.En el Capítulo 2 se describe la síntesis y caracterización de un complejo macrocíclico de tetra-Zn(salphen), utilizando una aproximación modelo del metal. El complejo macrocíclico de Zn muestra un fuerte auto-ensamblaje en comparación con una serie de compuestos de referencia/modelo.El proceso de auto-ensamblaje está mediado por la formación de unidades diméricas intermoleculares de Zn(salphen) que se mantienen unidos a través de puentes μ2-fenoxo (Esquema 2). Los experimentos de valoración competitiva UV-vis/fluorescencia sugieren que un aumento molecular del número de unidades de Zn(salphen) eselresponsable de una formación fuerte de agregados supramoleculares, y que la desagregación está acompañada por un fuerte efecto hipercrómico. El fuerte auto-ensamblajedel complejo macrocíclico de tetra-Zn(salphen) estátambién soportado por estudios de RMN, espectrometría de masas y estudios de microscopía electrónica de transmisión (TEM). Esquema 2.A la izquierda la estructura del complejo macrocíclico detetra-Zn(salphen), a la derecha, la naturaleza dimérica de auto-ensamblaje mostradapor las unidades estándar de Zn(salphen).El capítulo 3 representa un estudio sobre el auto-ensamblaje extremadamente fuerte de un complejo de bis-Zn(salphen) tanto en solución, así como en una interfase sólido-líquido. Las moléculas de bis-Zn(salphen) han demostrado auto-organizarse en agregados oligoméricos extremadamente estables(Figura 1), que no pueden ser disociados por la adición de ligandos donantes. Este comportamiento en la interfase líquido-sólido ha demostrado estar en excelente acuerdo con los estudios de soluciones: valoraciones competitivas con UV-Vis y fluorescencia, dispersión de luz dinámica (DLS) y microscopía electrónica de transmisión (TEM). El análisis a nivel DFT llevado a cabo para el complejobis-Zn(salphen) muestra que opera un modo de unión inusual, y también racionaliza la alta estabilidad de las estructuras auto-ensambladas provocadas por motivos de coordinaciónoligomérica (ZnO)ndentro delconjunto (oligomérico). Este modo de coordinación es sorprendentemente diferente en comparación con los análogos mononucleares de Zn(salphen),los cuales forman estructuras diméricas que tienen una unidad central típica Zn2O2(Esquema 2 a la derecha). Por lo tanto, la alta estabilidad de la estructura multinuclear representa una gran promesa para el desarrollo de materiales de auto-ensamblaje estables con potencial para la obtención de nuevos materiales opto-electrónicos. Figura 1.A la izquierda,la estructura de los complejos de bis-Zn(salphen).En el centro, la imagen STM del agregado oligomérico; a la derecha, el modo de auto-ensamblaje del conjunto pentamérico muestra las cadenas oligoméricas (Zn-O)n entre las unidades de bis-Zn(salphen), (optimización en DFT).El capítulo 4reporta la síntesis de una nueva clase de complejos de Zn(II) de bases de Schiff que incorporan una unidad de fenazina en la cadena principal (designados como compuestos de "salphenazina"). Los complejos de salphenazina muestran propiedades fotofísicas interesantes, en comparación con los complejos de salen y salphen típicos, sin dejar de ser fácilmente sintetizados y ajustables. A partir de los datos de UV-Vis experimentales y teóricos, las bandas de absorción han sido asignadas a transiciones-* que están directamente influenciadas por el tipo de sustituyente presente en el armazón de la salphenazina (Figura 2). Por lo tanto, a través de una elección sensata de estos grupos, es posible obtener sistemas de propiedades fotofísicas deseados. Los Complejos de Zn(salphenazina) también han demostrado que tienen potencial aplicación en las células solares orgánicas de moléculas pequeñas (smOSCs), debido a su alta estabilidad y propiedades electrónicas adecuadas contra el aceptor C60. A pesar de que la eficiencia del dispositivo todavía no es competitiva, los complejos de Zn(salphenazina) muestran el potencial sintético para una mejora significativa sobre la base de la construcción modular de estos complejos foto-activos. Figura2. Estructura del complejo de Zn(salphenazina) (a la izquierda), y una transición-* seleccionada, representada por mapas de densidad electrónica diferencial EDDM (a la derecha).El capítulo 5reporta un estudio DFT detallado del mecanismo de reacción de la adición de expansión de anillo de CO2 a epóxidos, catalizada por un sistema binario compuesto por un complejo Zn(salphen) y NBu4X(X = Br, I). La reacción catalítica se ha estudiado en detalle describiendo sus tres pasos principales: la apertura del anillo del epóxido, la etapa de inserción de CO2 y un final cierre del anillo para la formación de carbonatos cíclicos de cinco miembros. Se examinó la etapa de apertura de anillo estableciendo la preferencia para la apertura del mismo en el carbono del metileno (C) o en el carbono del metino (C). También se exploró la inserción de CO2 y el cierre del anillo para seis distintos epóxidos sustituidos, resultando ser significativamente más difícil en comparación con la etapa de apertura del anillo. Los resultados combinados han ayudado a explicar anteriores observaciones experimentales y limitaciones del catalizador. Esquema 3.La adición de expansión de anillo de CO2 con epóxidos (substratos 1-6 usados en esta investigación) para la generación de carbonatos cíclicos de cinco miembros, usando el catalizador binario compuesto por Zn(salphen) (Cat) y NBu4X (X = I, Br). / “Salen” ligands are relatively planartetradentate, N2O2-coordinating ligand systems which are obtained by the condensation reaction of readily available diamine and (substituted) salicylaldehyde precursors. Metallosalen complexes combine a number of advantages such as ease of variation in steric and electronic features, and the use of modular strategies that enable manipulation of different fragments of the ligand systems. Metal-derived salen complexes are versatile and they have proven to be effective catalysts for many asymmetric conversions including (ep)oxidations, epoxide ring-opening reactions and stereo-selective polymerizations. Lately, phenyl-bridged salen ligands (designated as “salphens” or “salophens”, Scheme 1) and related structures have started to raise the attention of the scientific community due to their particular advantages over their salen analogues; they represent π-conjugated ligand systems with tuneable photophysical properties, and are more cost-effective than the corresponding (chiral) salen ligands. For these reasons, such salphen systems have excellent potential as building blocks in material science amongst other applications. Scheme 1.Schematic drawing of a salphen ligand showing the N2O2 metal binding pocket and the various possibilities for substitution thereof.It should also be noted that the rigid geometry around the metal centre, dictated by the salphen ligand, can be used to manipulate properties such as the Lewis acid character of the metal and therefore it can be effectively applied to increase the reactivity, substrate binding properties and self-assembly behaviour of the resulting complex. Thus, the work reported in this thesis has principally focused on the study of novel self-assembly features and patterns, and on the development of other new application ofZn(salphen) complexes.The first two chapters (2 and 3) present detailed studies on the self-assembly of different multinuclear Zn(salphen)s focusing on the type and the strength of the interactions involved. In Chapter 2the synthesis and characterization of a tetra-Zn(salphen) macrocycleusing a metal template approachis described. The macrocyclic Zn complex shows strong self-assembly in comparison to a number of reference/model compounds. The self-assembly process is mediated by the formation of intermolecular dimericZn(salphen) units that are held together via μ2-phenoxo bridges (Scheme 2). Competitive UV-Vis/fluorescence titration experiments suggest that a molecular increase of the number of Zn(salphen) units is responsible for the formation of more stable supramolecular aggregates, and de-aggregation is accompanied by a strong hyperchromic effect. The strong self-assembly behaviour of the tetra-Zn(salphen) macrocyclewas further supported by NMR, mass spectrometry and transmission electron microscopy (TEM) studies. Scheme 2. On the left, line drawing of the tetra-Zn(salphen) macrocycle; on the right,a dimeric self-assembled Zn(salphen) complex showing the involved ZnO coordinative bonds.Chapter 3represents a study on the extremely strong self-assembly of a bis-Zn(salphen) complex both in solution as well as at a solid-liquid interface. The bis-Zn(salphen) molecules are shown to self-organize into extremely stable, edge-on orientated oligomeric aggregates (Figure 1), which could not be dissociated by addition of (small amounts of) donating ligands. This behaviour at the liquid-solid interface has demonstrated to be in excellent agreement with solution studies: competitive UV-Vis and fluorescence titrations, dynamic light scattering (DLS) and transmission electron microscopy (TEM) experiments are also in line with a highly increased stability for the assembled state of these bis-Zn(salphen)s. DFT analysis carried out for thebis-Zn(salphen) shows that an unusual binding mode is operative, and also rationalizes the very high stability of the self-assembled structures provoked by oligomeric (ZnO)n coordination motifs within the (oligomeric) assembly. This coordination mode is strikingly different when compared with mononuclear Zn(salphen) analogues that form dimeric structures having a typical Zn2O2 central unit (Scheme 2 on the right). The high stability of the multinuclear structure therefore holds great promise for the development of stable self-assembled monolayers (SAMs) with potential for new opto-electronic materials. Figure 1.On the left, line drawing of the bis-Zn(salphen) complexes. In the central part, section of the STM image of an oligomeric aggregate; on the right, the most likely self-assembly mode of a pentameric assembly showing the (Zn-O)noligomeric chains between the individual bis-Zn(salphen) units (DFT optimization).Chapter 4reports the synthesis of a new class of Zn(II) Schiff base complex incorporating a phenazine unit in the backbone and is designated as “Zn(salphenazine)”. These Zn(salphenazine) complexes show interesting photophysical properties compared to typical salen and salphen complexes while remaining easily synthesized and tuneable. From the experimental and theoretical UV-Vis data, the absorption bands have been assigned to -* transitions which are directly influenced by the type of substituents present in the salphenazine scaffold (Figure 2). Therefore, by a judicious choice of these groups, it is possible to obtain systems with desired photophysical properties. Zn(salphenazine) complexes have also shown to have potential application in small molecule Organic Solar Cells (smOSCs) due to their high stability and adequate electronic properties against the acceptor C60. Even though the efficiency of the device is not competitive yet, Zn(salphenazine)s show the synthetic potential for significant improvement based on the modular construction of these photo-active complexes. Figure 2. Schematic drawing of a Zn(salphenazine) complex (on the left) and a selected -* transition represented with electron density difference map EDDM (on the right). Scheme 3.The ring-expansion addition of CO2 to epoxides (substrates 1-6 used in this investigation) generating five-membered cyclic carbonates using a binary catalyst composed of a Zn(salphen) component (cf., Cat) and NBu4X (X = I, Br).Chapter 5reports a detailed DFT study of the reaction mechanism of the ring-expansion addition of CO2to epoxides catalyzed by a binary catalyst comprising a Zn(salphen) complex and co-catalytic NBu4X (X=Br, I). The catalytic reaction has been studied in detail describing the three main steps involved: the epoxide ring-opening, the CO2 insertion step and a final ring-closurestep to afford the five-membered cyclic carbonate products. The ring-opening step of the process was examined and the preference for opening at the methylene (C) or methine carbon (C) was established. Also, the CO2 insertion and the ring-closing steps have been explored for six differently substituted epoxides and proved to be significantly more challenging compared with the ring-opening step. The combined results have helped to explain earlier experimental observations and catalyst limitations, and are useful for improved catalyst design and development.