Photochemistry and photophysics of chemical and biologically relevant systems: mechanisms, dynamics and methodologies

El proyecto presentado en esta Tesis se basa en la aplicación y desarrollo de métodos teóricos y computacionales con el fin de describir la fotoquímica y la fotofísica de compuestos moleculares químicos y de relevancia biológica. Más detalladamente, se lograron los siguientes objetivos: i.Aplicación de la metodología CASPT2//CASSCF al estudio de un modelo de la conformación giro-beta, formado por dos glicinas enlazadas a través de un enlace de hidrógeno. Se consiguieron calcular los caminos de mínima energía encontrados a partir de la irradiación UV que permiten finalmente, la disipación de la energía de excitación como energía vibracional. ii.Aplicación de la metodología CASPT2//CASSCF/AMBER al estudio de mecanismos de fotoestabilidad en la proteína gamma-B-cristalina, que forma (junto con otras proteínas cristalinas) el cristalino del ojo humano. Especialmente, se destaca el papel que puede jugar el elemento denominado "Tyrosine corner", una parte seleccionada de la cadena proteica que permite un giro de aproximadamente 180? a través de un enlace de hidrógeno entre la cadena principal y el grupo lateral de una tirosina. iii.Desarrollo de un método de determinación cuantitativa de la energía de excitación de un cromóforo con diferente sustitución, en el caso de que la sustitución química afecte al cromóforo solo a nivel estructural y no a la naturaleza electrónica del estado excitado considerado. iv.Tratamiento de los efectos del entorno sobre un interruptor molecular inducido por luz, como fuerzas externas que actúan en los dos extremos del cromóforo. En el caso del azobenceno (uno de los interruptores moleculares inducidos por luz más empleado), los isómeros cis y trans muestran una fotosensibilidad considerable respecto a las fuerzas aplicadas, permitiendo la modulación de la longitud de onda del máximo de absorción

Photochemistry and photophysics of chemical and biologically relevant systems: mechanisms, dynamics and methodologies

El proyecto presentado en esta Tesis se basa en la aplicación y desarrollo de métodos teóricos y computacionales con el fin de describir la fotoquímica y la fotofísica de compuestos moleculares químicos y de relevancia biológica. Más detalladamente, se lograron los siguientes objetivos: i.Aplicación de la metodología CASPT2//CASSCF al estudio de un modelo de la conformación giro-beta, formado por dos glicinas enlazadas a través de un enlace de hidrógeno. Se consiguieron calcular los caminos de mínima energía encontrados a partir de la irradiación UV que permiten finalmente, la disipación de la energía de excitación como energía vibracional. ii.Aplicación de la metodología CASPT2//CASSCF/AMBER al estudio de mecanismos de fotoestabilidad en la proteína gamma-B-cristalina, que forma (junto con otras proteínas cristalinas) el cristalino del ojo humano. Especialmente, se destaca el papel que puede jugar el elemento denominado "Tyrosine corner", una parte seleccionada de la cadena proteica que permite un giro de aproximadamente 180? a través de un enlace de hidrógeno entre la cadena principal y el grupo lateral de una tirosina. iii.Desarrollo de un método de determinación cuantitativa de la energía de excitación de un cromóforo con diferente sustitución, en el caso de que la sustitución química afecte al cromóforo solo a nivel estructural y no a la naturaleza electrónica del estado excitado considerado. iv.Tratamiento de los efectos del entorno sobre un interruptor molecular inducido por luz, como fuerzas externas que actúan en los dos extremos del cromóforo. En el caso del azobenceno (uno de los interruptores moleculares inducidos por luz más empleado), los isómeros cis y trans muestran una fotosensibilidad considerable respecto a las fuerzas aplicadas, permitiendo la modulación de la longitud de onda del máximo de absorción

Taking up the quest for novel molecular solar thermal systems: Pros and cons of storing energy with cubane and cubadiene

Molecular solar thermal (MOST) systems are working their way as a possible technology to store solar light and release it when necessary. Such systems could, in principle, constitute a solution to the energy storage problem characteristic of solar cells and are conceived, at a first instance, as simple molecular photoswitches. Nevertheless, the optimization of their different required properties is presently limiting their technological scale up. From the chemical perspective, we need to design a novel MOST system based on unconventional photoswitches. Here, by applying multi-configurational quantum chemistry methods, we unravel the potentialities of ad hoc-designed molecular photoswitches, which aim to photoproduce cubane or cubadiene as high-energy isomers that can be thermally (or eventually catalytically) reverted to the initial structure, releasing their stored energy. Specifically, while cubane can be photoproduced via different paths depending on the reactant tricycle diene conformation, an undesired bicyclic by-product limits its application to MOST systems. An evolution of this starting design toward cubadiene formation is therefore proposed, avoiding conformational equilibria and by-products, considerably red shifting the absorption to reach the visible portion of the solar spectrum and maintaining an estimated storage density that is expected to overcome the current MOST reference system (norbornadiene/quadricyclane), although consistently increasing the photoisomerization energy barrier

Competing ultrafast photoinduced electron transfer and intersystem crossing of [Re(CO)(3)(Dmp)(His124)(Trp122)]+ in Pseudomonas aeruginosa azurin:a nonadiabatic dynamics study

We present a computational study of sub-picosecond nonadiabatic dynamics in a rhenium complex coupled electronically to a tryptophan (Trp) side chain of Pseudomonas aeruginosa azurin, a prototypical protein used in the study of electron transfer in proteins. To gain a comprehensive understanding of the photoinduced processes in this system, we have carried out vertical excitation calculations at the TDDFT level of theory as well as nonadiabatic dynamics simulations using the surface hopping including arbitrary couplings (SHARC) method coupled to potential energy surfaces represented with a linear vibronic coupling model. The results show that the initial photoexcitation populates both singlet metal-to-ligand charge transfer (MLCT) and singlet charge-separated (CS) states, where in the latter an electron was transferred from the Trp amino acid to the complex. Subsequently, a complex mechanism of simultaneous intersystem crossing and electron transfer leads to the sub-picosecond population of triplet MLCT and triplet CS states. These results confirm the assignment of the sub-ps time constants of previous experimental studies and constitute the first computational evidence for the ultrafast formation of the charge-separated states in Re-sensitized azurin

π‐Bridge Substitution in DASAs: The Subtle Equilibrium between Photochemical Improvements and Thermal Control

Donor-acceptor Stenhouse adducts (DASAs) are playing an outstanding role as innovative and versatile photoswitches. Until now, all the efforts have been spent on modifying the donor and acceptor moieties to modulate the absorption energy and improve the cyclization and reversion kinetics. However, there is a strong dependence on specific structural modifications and a lack of predictive behavior, mostly owing to the complex photoswitching mechanism. Here, by means of a combined experimental and theoretical study, the effect of chemical modification of the pi-bridge linking the donor and acceptor moieties is systematically explored, revealing the significant impact on the absorption, photocyclization, and relative stability of the open form. In particular, a position along the pi-bridge is found to be the most suited to redshift the absorption while preserving the cyclization. However, thermal back-reaction to the initial isomer is blocked. These effects are explained in terms of an increased acceptor capability offered by the pi-bridge substituent that can be modulated. This strategy opens the path toward derivatives with infra-red absorption and a potential anchoring point for further functionalization

Photoinduced Proton Transfer as a Possible Mechanism for Highly Efficient Excited-State Deactivation in Proteins

CASSCF//CASPT2 pathways for a two-glycine minimal model system show that photoinduced electron-driven forward and backward proton transfer could play an important role for the stability of proteins against damage by UV radiation, when a hydrogen bond is located between the two amino acids. The overall photoinduced process involves two electron and proton transfer processes (forward and backward) and results in the reformation of the initial closed-shell electronic structure of the system.Ministerio de Educación y CienciaUniversidad de Alcal

Chiral Hydrogen Bond Environment Providing Unidirectional Rotation in Photoactive Molecular Motors

Generation of a chiral hydrogen bond environment in efficient molecular photoswitches is proposed as a novel strategy for the design of photoactive molecular motors. Here, the following strategy is used to design a retinal-based motor presenting singular properties: (i) a single excitation wavelength is needed to complete the unidirectional rotation process (360°); (ii) the absence of any thermal step permits the process to take place at low temperatures; and (iii) the ultrafast process permits high rotational frequencies.Ministerio de Economía y CompetitividadMinisterio de Ciencia e InnovaciónUniversidad de Alcal

Low mortality rates at two years in HIV-infected individuals undergoing systematic tuberculosis testing with rapid assays at initiation of antiretroviral treatment in Mozambique

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Thermodynamics of the interaction between spike protein of severe acute respiratory syndrome-coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 1000000 deaths all over the world and still lacks a medical treatment despite the attention of the whole scientific community. Human angiotensin-converting enzyme 2 (ACE2) was recently recognized as the transmembrane protein that serves as the point of entry of SARS-CoV-2 into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the protein complex. Moreover, the free energy of binding between ACE2 and the active receptor binding domain of the SARS-CoV-2 spike protein is evaluated quantitatively, providing for the first time the thermodynamics of virus?receptor recognition. Furthermore, the action of different ACE2 ligands is also examined in particular in their capacity to disrupt SARS-CoV-2 recognition, also providing via a free energy profile the quantification of the ligand-induced decreased affinity. These results improve our knowledge on molecular grounds of the SARS-CoV-2 infection and allow us to suggest rationales that could be useful for the subsequent wise molecular design for the treatment of COVID-19 cases