Quantum chemistry and metadynamics study of kinetic routes to alanine formation by CO or CO2 insertions in E- or Z-ethanimine isomers

• Published in: Atti della Accademia nazionale dei Lincei. Rendiconti Lincei. Scienze fisiche e naturali Vol. 34; no. 4; pp. 1021 - 1030
• Main Authors: Nogueira-da-Silva, Matheus A. R., Coutinho, Nayara D., da Silva, Wender A., Carvalho-Silva, Valter H.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2023; Springer Nature B.V
• Subjects: Alanine; Amino acids; Atmospheric chemistry; Biological evolution; Biomedicine; Carbon dioxide; Carbon monoxide; Chemical evolution; Chemical Kinetics at micro; Chirality; Earth and Environmental Science; Earth Sciences; Environment; First principles; Glycine; History of Science; Isomers; Life Sciences; macro-scales; Mathematical analysis; meso; meso-,macro-scales; Molecular dynamics; Pharmaceutical industry; Physics; Precursors; Quantum chemistry; Quantum mechanics; Simulation; Synthesis; Metadynamics; Stationary states; Homochirality; Amino acid synthesis; Reaction paths
• ISSN: 2037-4631; 1720-0776
• DOI: 10.1007/s12210-023-01199-5

Investigations of the synthesis of amino acids are crucial to the understanding of the chemical evolution of life and are of applied interest in biochemistry and pharmaceutical industry. Focus is here on extending the comprehension of their formation, studying by theoretical and computational procedures potential pathways for the synthesis of precursors of alanine. Amino acid is second in simplicity only to glycine and the simplest exhibiting chirality. Eight reaction paths were designed based on known experimental features and on theoretical grounds. For their study, stationary and dynamical quantum mechanical methods were used. For the first set of four reactions examined, E-ethanimine and Z-ethanimine reacted with carbon monoxide forming R- and S-alanine precursors, each process considered as evolving upon two planes of approach. For the other set of four reactions, the ethanimine isomers reacted with carbon dioxide. For all reactions, the chirality of the alanine precursors was also analyzed. Calculations of geometries and energies of the stationary points (reactants, products, van der Waals complexes and transition states) for all reactions were processed, as well as their thermodynamical state functions. The Z-ethanimine and CO reactions were found to be favored. Preferential channels for the chiral center formation were not identified. Biased first-principle molecular dynamics simulations (metadynamics) were carried out to provide the enantiomeric control of the reactions and the formation of other possible remarkable structures: initially 80 metadynamics simulations were performed. They confirmed the precursors of alanine found in the static calculations, but also found additional ones. In general, the last steps of the simulation culminated in simpler and less reactive substances. Our results individuated feasible reaction pathways to precursors of alanine synthesis, although no evidence was obtained of favoring homochiral selectivity. However, insertion of CO and CO 2 into ethanimines was considered, with these molecules being of primordial interest, and both were shown to be orientable in gaseous flow, so arguably relevant to the emergence of chirality by a stereodynamic mechanism.