Vitamin-V: Virtual Environment and Tool-boxing for Trustworthy Development of RISC-V based Cloud Services

Vitamin-V is a 2023-2025 Horizon Europe project that aims to develop a complete RISC-V open-source software stack for cloud services with comparable performance to the cloud-dominant x86 counterpart and a powerful virtual execution environment for software development, validation, verification, and test that considers the relevant RISC-V ISA extensions for cloud deployment

Development of structurally and electronally versatile aminopyridine cobalt complexes for photo-(electro) reduction of water and ketones

The increasing need for more efficient synthetic methods and sustainable processes for fuel and high-value organic molecules production can be seen as one of the major challenging goals for the future. Nature has developed a sophisticated system to store the light energy into chemical bonds. The mimicking of the natural systems through the development of artificial photosynthetic schemes is extremely interesting since it could effort green reduction alternatives. Toward this end, in this thesis we describe a new family of cobalt complexes based on aminopyridine ligands able to reduce protons and ketones under photochemical conditions. Additionally, the same catalytic systems were found active for the electrocatalytic proton reduction to H2. Ligand availability, modularity and versatility of this type of coordination complexes let us to tune the first coordination sphere of the metal by changing the electronic and structural features of the ligand. This allows us to pinpointing preferred ligand structures to sustain efficient H2 and alcohol production. In addition, the straightforward tuning of the ligand nature let to modulate or even alter the selectivity proton-ketone reduction. The high modularity of these systems also allows to modify the secondary coordination sphere of metal center. In this way, the functionalization of cobalt systems with a biotin moiety bring us to encapsulate the cobalt catalyst system into a protein environment. We prove that the natural pocket enhances the reactivity in water reduction to H2. Mechanistic studies and characterization of the intermediates have been pursued, with the aim of understanding the requirements for a better design of cobalt-based catalysts. Spectroscopic, magnetic and NMR experiments, along with DFT calculations suggest that the CoI intermediate with the Py2Tstacn ligand shows an important electron density over the pyridine moiety, leading to a formal CoII metal center. Finally, using fluorescence quenching, UV/Vis, electrochemical, kinetic and isotope labelling experiments the mechanism in the photocatalytic ketone reduction is constructed. Supported by DFT calculations, a heterolytic pathway for ketone reduction seems to be preferred, although the contribution of a homolytic pathway could not be fully ruled out. This thesis paves the way for the construction of more active cobalt based catalytic systems for light-driven reduction reactionsLa creixent necessitat de sistemes sintètics més eficients i procesos sostenibles per la producción de combustibles i molècules orgàniques d’alt valor afegit, pot ser vist com una de les principals fites més desafiants pel futur. La natura ha desenvolupat un sofisticat sistema per emmagatzemar l’energia llumínica en forma d’enllaços químics. La imitació dels sistemes naturals mitjançant el desenvolupament d’esquemes artificials és summament interessant, que ja podria proporcionar alternatives ecològiques de reducció. Amb aquesta finalitat, en aquesta tesi descrivim una nova família de complexos de cobalt basats en lligands aminopiridinics capaços de reduir els protons i cetones en condicions fotoquímiques. A més, el mateixos sistemes catalítics també són actius en la formació d’hidrogen electrocatalítica. La disponibilitat del lligand, la modularitat i la versatilitat d'aquest família de complexos de coordinació ens permeten també tunejar la primera esfera de coordinació del metall a través de la modificació de les característiques electròniques i estructurals del lligand. Això ens permet la identificació de les estructures del lligand preferides per a dur a terme de producció eficient d’hidrogen i alcohol. A més a més, la modificació directa de la naturalesa del lligand permet modular o fins i tot alterar la selectivitat protó-cetona en la reducció. L'alta modularitat d'aquests sistemes també permet modificar la segona esfera de coordinació del centre metàl·lic. En aquest sentit, la funcionalització de sistemes de cobalt amb un fragment de biotina ens concedeix la possibilitat d’encapsular el sistema catalític en un entorn proteic. Es demostra que la presència de la cavitat proteica proporciona una millora en l’eficiència de reducció de l’aigua a H2. S’han realitzat estudis mecanístics i s’han caracteritzat els intermedis de reacció amb el propòsit d’entendre els requisits principals per un millor disseny de catalitzadors. Experiments basats en espectroscòpia, magnetisme i de ressonància magnètica nuclear, juntament amb càlculs DFT han suggerit que l’intermedi de CoI amb el lligand Py2Tstacn presenta una densitat electrònica important en la piridina del lligand, fet que condueix a un centre formal de CoII. Finalment, utilitzant experiments de mesura de fluorescència, UV/Vis, electroquímica i experiments de marcatge isotòpic hem pogut construir el mecanisme de reducció de cetones impulsat per la energia llumínica. Amb el suport de càlculs teòrics, sembla ser que el mecanisme heterolític és el preferit, i tot que no es pot descartar la contribució d’una via homolítica. Aquesta tesi aplana el camí per a la construcció de sistemes catalítics basats en cobalt més actius en reaccions de reducció impulsades per l’energia llumínicaPrograma de Doctorat en Ciències Experimentals i Sostenibilita

Enhance and Control of the Selectivity in Light-driven Ketone versus Water Reduction Using Aminopyridine Cobalt Complexes

Cobalt(II) complexes with the general structure [CoII(OTf)(Y,XPy2Tstacn)](OTf) (1R, where Y,XPy2Tstacn is 1,4-di(p-Y,m-X-picolyl)-7-R-1,4,7-triazacyclononane; 1H, 1CO2Et, 1DMM) and [CoII(OTf)2(Y,XPyMetacn)] (2R, where Y,XPyMetacn is 1-(p-Y,m-X-picolyl)-7,4-di-methyl-1,4,7-triazacyclononane; 2CO2Et, 2Cl, 2H, 2DMM, 2NMe2) were active in both light-driven acetophenone (3a) and water reduction. Competition studies show that aromatic ketone/water reduction selectivity ranks from 0.2 to 8.0. Nevertheless, considering the concentrations of water and ketone in catalysis (ratio H2O/3a ∼ 2000) the highest selectivity obtained is greater than 15 000. The selectivity correlates well with the CoI/II redox potential within the same cobalt catalyst series (span 240 mV (1R) and 290 mV (2R)), with electron donating ligands favoring ketone reduction over H2 evolution. Based on this finding, the operative mechanism for the reduction of aromatic ketones is consistent with a single electron transfer (SET) followed by a hydrogen atom transfer (HAT) mechanism. This new insight will be a guide to develop selective catalytic systems to produce fine solar chemicals in water

Catalizadores para la conversión de la energía solar en enlaces químicos

El desarrollo de métodos sintéticos limpios y sostenibles que utilicen la luz solar como fuente de energía sin comprometer el medio ambiente ni los recursos naturales del planeta es un gran reto científico y tecnológico. Actualmente nuestra sociedad se nutre principalmente de energía y compuestos químicos derivados del carbón, gas natural y petróleo. Estas materias primas no son renovables, pues provienen de procesos fotosintéticos llevados a cabo desde el cámbrico y su posterior transformación geológica. Además, su uso intensivo como vector energético durante los últimos 200 años (Figura 1) ha elevado la concentración de CO2 en la atmosfera de 280 a 400 ppm, posiblemente una de las causas del cambio climático.[1] La transformación de la energía solar (renovable, abundante y económica) en energía química es una de las alternativas más atractivas; pues la tierra recibe anualmente 20.000 veces más energía de la que consume la sociedad. Este tipo de energía ofrece la ventaja de poder ser fácilmente almacenada y transportada, pudiendo ser utilizada según la demanda. Un ejemplo de su potencial lo demuestran las plantas y algas verdes, que producen compuestos químicos de alto valor energético a partir de luz solar, H2 O y CO2 en condiciones de temperatura y presión ambiente.[2] Este proceso de captura y conversión de luz solar en potencial químico se da durante la fotosíntesis y mantiene la vida en la tierra

C–H Bonds as Functional Groups: Simultaneous Generation of Multiple Stereocenters by Enantioselective Hydroxylation at Unactivated Tertiary C–H Bonds

Enantioselective C-H oxidation is a standing chemical challenge foreseen as a powerful tool to transform readily available organic molecules into precious oxygenated building blocks. Here, we describe a catalytic enantioselective hydroxylation of tertiary C-H bonds in cyclohexane scaffolds with H2O2, an evolved manganese catalyst that provides structural complementary to the substrate similarly to the lock-and-key recognition operating in enzymatic active sites. Theoretical calculations unveil that enantioselectivity is governed by the precise fitting of the substrate scaffold into the catalytic site, through a network of complementary weak non-covalent interactions. Stereoretentive C(sp3)-H hydroxylation results in a single-step generation of multiple stereogenic centers (up to 4) that can be orthogonally manipulated by conventional methods providing rapid access, from a single precursor to a variety of chiral scaffolds

Light-Driven Reduction of Aromatic Olefins in Aqueous Media Catalysed by Aminopyridine Cobalt Complexes.

A catalytic system based on earth-abundant elements that efficiently hydrogenates aryl olefins using visible light as driving-force and H2O as the sole hydrogen atoms source is reported. The catalytic system involves a robust and well-defined aminopyridine cobalt complex and a heteroleptic Cu photoredox catalyst. The system shows the reduction of styrene in aqueous media with a remarkable selectivity (> 20000) versus water reduction (WR). Reactivity and mechanistic studies support the formation of a [Co-H] intermediate, which reacts as a hydrogen transfer agent (HAT). Synthetically useful deuterium-labelled compounds can be straightforwardly obtained by replacing H2O with D2O and using only catalysts based on earth-abundant elements. Moreover, the dual photocatalytic system and the photocatalytic conditions can be rationally designed to tune the selectivity for aryl olefin vs aryl ketone reduction; not only by changing the structural and electronic properties of the cobalt catalysts, but also by modifying the reduction properties of the light-harvesting syste

An investigation of steric influence on the reactivity of FeV(O)(OH) tautomers in stereospecific C-H hydroxylation

Two new tetradentate N4 ligands (LN4), LN4 = Me2,Me2PyzTACN (1-(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)-4,7-dimethyl-1,4,7-triazacyclononane) and Me2,MeImTACN (1-((1-methyl-1H-imidazol-1-yl)methyl)-4,7-dimethyl-1,4,7-triazacyclononane) have been synthesized and their corresponding Fe(ii) complexes [FeII(Me2,Me2PyzTACN)(CF3SO3)2], 1Pz, and [FeII(Me2,MeImTACN)(CF3SO3)2], 1Im, have been prepared and characterized. Complexes 1Pz and 1Im catalyse the hydroxylation of C-H bonds of alkanes with excellent efficiencies, using hydrogen peroxide as oxidant. The high H/D kinetic isotope effect values for C-H hydroxylation, large normalized tertiary/secondary C-H (C3/C2) bond selectivities in adamantane oxidation, and high degrees of stereoretention in the oxidation of cis-1,2-dimethylcyclohexane are indicative of metal-based oxidation processes. The complexes also catalyse the oxidation of cyclooctene to form its corresponding epoxide and syn-diol. For 1Pz the epoxide is the main product, while for the analogous complex 1Im the syn-diol predominates. The active oxidant is proposed to be an [(LN4)FeV(O)(OH)]2+ species (2Pz, LN4 = Me2,Me2PyzTACN and 2Im, LN4 = Me2,MeImTACN) which may exist in two tautomeric forms related by a proton shift between the oxo and hydroxo ligands. Isotope labelling experiments show that the oxygen atom in the hydroxylated products originates from both water and hydrogen peroxide, and labelling experiments involving oxygen atom transfer to sterically bulky substrates provide indirect information on the steric influence exerted by the two ligands in the relative reactivities of the two hypervalent iron tautomers. Based on these labelling studies, the steric influence exerted by each of the ligands towards the relative reactivity of the oxo ligands of the corresponding pair of Fe(v)(O)(OH) tautomers can be derived. Furthermore, this steric influence can be gauged relative to related complexes/ligands

Understanding light-driven H2 evolution through the electronic tuning of aminopyridine cobalt complexes

A new family of cobalt complexes with the general formula [CoII(OTf)2(Y,XPyMetacn)] (1R, Y,XPyMetacn = 1-[(4-X-3,5-Y-2-pyridyl)methyl]-4,7-dimethyl-1,4,7-triazacyclononane, (X = CN (1CN), CO2Et (1CO2Et), Cl (1Cl), H (1H), NMe2 (1NMe2)) where (Y = H, and X = OMe when Y = Me (1DMM)) is reported. We found that the electronic tuning of the Y,XPyMetacn ligand not only has an impact on the electronic and structural properties of the metal center, but also allows for a systematic water-reduction-catalytic control. In particular, the increase of the electron-withdrawing character of the pyridine moiety promotes a 20-fold enhancement of the catalytic outcome. By UV-Vis spectroscopy, luminescence quenching studies and Transient Absorption Spectroscopy (TAS), we have studied the direct reaction of the photogenerated [IrIII(ppy)2(bpy˙−)] (PSIr) species to form the elusive CoI intermediates. In particular, our attention is focused on the effect of the ligand architecture in this elemental step of the catalytic mechanism. Finally, kinetic isotopic experiments together with DFT calculations provide complementary information about the rate-determining step of the catalytic cycle

Improved Electro- and Photocatalytic Water Reduction by Confined Cobalt Catalysts in Streptavidin

Incorporation of biotinylated aminopyridine cobalt complexes derived from the triazacyclononane scaffold into the streptavidin protein leads to formation of artificial metalloenzymes for water reduction to hydrogen. The synthesized artificial metalloenzymes have lower overpotential (at the half-peak up to 100 mV) and higher photocatalytic hydrogen evolution activity (up to 14- and 10-fold increase in TOF and TON, respectively, at pH 12.5) than the free biotinylated cobalt complexes. 1H-NMR, EPR and XAS highlight the presence of the metal complexes upon supramolecular attachment to the streptavidin. pHdependent catalytic studies and molecular dynamics (MD) simulations suggest that the increase in the catalytic activity could be induced by the protein residues positioned close to the metal centers. These findings illustrate the ability of the biotin−streptavidin technology to produce artificial metalloproteins for photo- and electrocatalytic hydrogen evolution reaction

Highly Enantioselective Catalytic Lactonization at Nonactivated Primary and Secondary γ-C–H Bonds

Chiral oxygenated aliphatic moieties are recurrent in biological and pharmaceutically relevant molecules and constitute one of the most versatile types of functionalities for further elaboration. Herein we report a protocol for straightforward and general access to chiral γ-lactones via enantioselective oxidation of strong nonactivated primary and secondary C(sp3)-H bonds in readily available carboxylic acids. The key enabling aspect is the use of robust sterically encumbered manganese catalysts that provide outstanding enantioselectivities (up to >99.9%) and yields (up to 96%) employing hydrogen peroxide as the oxidant. The resulting γ-lactones are of immediate interest for the preparation of inter alia natural products and recyclable polymeric materials