Estudo de reações de formação de nucleotídeos – uma investigação teórico-computacional das propostas do RNA-World

Abstract

The origin of life on Earth is a widely debated interdisciplinary topic, whose central hypothesis is associated with chemical evolution. This proposal suggests that life may have emerged from reactions among compounds present on the primitive Earth over time. However, in attempting to answer how life arose, this hypothesis raises new fundamental questions, such as the emergence of the genetic code. In this context, the RNA World theory appears as the most promising explanation for genetic origins, postulating that prebiotic reactions led to the formation of rudimentary RNA strands from nucleotides, which later evolved into more complex structures. Despite its potential, this theory faces criticism related to the low yield of nucleotide formation and the instability of their reactions in aqueous medium, considering the reactional system with its fundamental building blocks, nucleobases (adenine, guanine, cytosine, and uracil), fosfatos (H₃PO₄, H₂PO₄⁻, HPO₄²⁻, PO₄³⁻), and the sugar D-ribose. In light of these limitations, theoretical studies have sought to explore the energetic properties of the reactions involved in nucleotide synthesis, proposing new reaction pathways for the prebiotic origin of life. Within this framework, the present study aims to investigate the spontaneity of nucleotide formation reactions from their fundamental building blocks, both in the gas phase and in aqueous solution. For this purpose, the B3LYP and M06-2X functionals were employed, with the 6-311+G(2d,p) basis set, in order to characterize molecular structures, thermodynamic and kinetic properties, and to assess the feasibility of the reactions in both environments. Additionally, chemical reactivity indices and Parr functions were explored to identify plausible reaction mechanisms. The results confirm the instability of reactions in aqueous solution, evidenced by the reduction in the number of possible processes compared to the gas phase and by the high kinetic barriers observed in the presence of water. Although some nucleotide formations of adenine, guanine, cytosine, and uracil appear to be spontaneous in the gas phase, the difficulty in explaining the presence of their reagents in this environment persists. As for the mechanisms, reactions between nucleobases and D-ribose tend to follow an SN1 pathway, in which water loss from ribose generates an oxocarbenium cation. Meanwhile, reactions between D-ribose and fosfatos may occur either through an SN1 pathway, with the formation of a metafosfato intermediate, or through an SN2 pathway, characterized by direct attack between the reactants. The ideal pH for such reactions ranges from slightly acidic to basic.