Autocatalysis in Formose Reaction and Formation of RNA Nucleosides

Understanding of the abiotic formation of nucleosides under geochemical conditions is currently a major scientific challenge. In this study, free radical pathways for formation of RNA nucleosides with canonical nucleobases are proposed for the first time. The pathways proceed with relatively low energy barriers for the formation of ribose as well as all RNA nucleosides. The formose reaction proceeds either with or without Ca²⁺ and CaOH⁺ cations. An autocalytic cycle for the formation of both glycolaldehyde and glyceraldehyde is identified when Ca²⁺ or CaOH⁺ cations are involved in the reaction. The results suggest that Ca²⁺ cations are not involved in the formation of ribose from glyceraldehyde. In addition, these pathways lead to the formation of dihydroxyacetone and d-erythrose. Calculated results show that the glycosidic bond can be formed abiotically between the d-ribose and the nucleobase, where d-ribose forms a cyclic free radical that subsequently reacts with the neutral nucleobase. Involvement of proper nucleobase tautomer is important for the formation of RNA nucleosides. Our approaches provide a solution for the long-standing question of how the glycosidic bond is formed under the abiotic conditions with low energy barriers. The pathways for formation of the sugars without a catalyst are relevant to the formation of sugars in interstellar clouds. On the other hand, the autocalysis in the formose reaction followed by the formation of the nucleosides is appropriate for the abiotic synthesis taking place in the presence of water in the early Earth environment. The Ca²⁺ and CaOH⁺ cations appear to be the first nonenzymatic catalytic systems for formation of biomolecules.