Novel synthetic and supramolecular approaches to prebiotic systems chemistry

• Autores: Noemí Nogal Rodríguez
• Directores de la Tesis: Andrés de la Escosura Navazo (dir. tes.)
• Lectura: En la Universidad Autónoma de Madrid ( España ) en 2024
• Idioma: inglés
• Número de páginas: 277
• Títulos paralelos:
  • Nuevos enfoques sintéticos y supramoleculares de la química de sistemas prebióticos
• Enlaces
  • Tesis en acceso abierto en: Biblos-e Archivo
• Resumen

  • The field of prebiotic chemistry has been dedicated for decades to finding abiotic routes to the molecular building blocks of life. Today a handful of prebiotically plausible scenarios exist that allow the laboratory synthesis of most amino acids, fatty acids, simple sugars, nucleotides and central metabolites of existing living organisms. The main bottleneck appears to be the self-organization of these elements into self-sustaining systems. In Chapter 1 of the present dissertation, the literature around the main synthetic pathways of prebiotic chemistry has been revised, suggesting how these might be related through common intermediates and catalytic cycles, as well as how recursive changes of conditions might help them to participate in self-organizing and dissipative networks/assemblies (i.e., systems that consume chemical or physical energy from their environment to maintain their internal organization in a dynamic steady state out of equilibrium). Also, in this first chapter attention is paid to some of the implications that such chemistry has for the emergence of homochirality. The connectivity between prebiotic pathways should form the basis of a strong research program toward the bottom-up implementation of protometabolic systems, taken as a central part of the problem of the origins of life. In Chapter 2, the experimental objectives set for the development of this doctoral thesis are established. Chapter 3 proposes a non-enzymatic synthetic route to obtain amino acids, consisting of the reductive amination of α-ketoacids in the presence of NADH, using as nitrogen source an aqueous solution of ammonia and ammonium, which could have taken place under primitive Earth conditions. The kinetics of the reaction are followed by NMR, as well as the quantification of the conversion of the α-ketoacid into the corresponding amino acid, employing for this purpose calibration lines of the analyte (the amino acid) at different concentrations with respect to an internal standard. Our studies have confirmed the formation of several amino acids (unambiguously identified by GC-MS), and the theoretical calculations used to elucidate the possible mechanism of the reaction are described. Chapter 4 deals with the same reaction developed in the previous chapter, but in this case the reductive amination of α-ketoacids is carried out in presence of dihydropyridine derivatives. We thus manage to shift the focus from a chemistry occurring in a more evolved context (which assumes the presence of biological cofactors) to a prebiotically plausible reaction where such complex redox agents could not assist it. For achievement of this goal, we have first synthesized the reduced form of different dihydropyridine derivatives as nicotinamide analogues, characterizing them by 1H-NMR, 13C-NMR, DEPT-135 and mass spectrometry. The reductive amination reaction was then carried out with the different dihydropyridines. The progress of the reaction was followed and quantified by NMR, while formation of the amino acids was confirmed by GC-MS. This has allowed the performance of a comparative study confirming the suitability of some of these reducing agents to promote a prebioticall plausible synthesis of amino acids that is fully consistent with current metabolic approaches to the generation of these important biomolecules. Finally, Chapter 5 focuses on the chemistry of supramolecular systems. In particular, new bioinspired supramolecular materials are synthesised in collaboration with Prof. Mathieu Surin. The materials consist of arylzopyrazole-derived molecular photoswitches containing a nucleobase (adenine or thymine) in their structure, which interacts through base-pairing with commercial oligonucleotides of different lengths. To characterise their formation, supramolecular organisation and response to light, a study was carried out by UV-Vis spectroscopy and circular dichroism, varying the medium conditions (e.g. ionic strength) as well as the DNA template used. This study has allowed us to observe selectivity in the chiral organisation of the resulting assemblies and an efficient chiroptical response to UV and/or blue light irradiation. Molecular dynamics calculations support the experimental observations and shed light on the interaction between the DNA strands and the molecular switch in both the trans and the cis forms