Prebiotic Origin of Pre‐RNA Building Blocks in a Urea “Warm Little Pond” Scenario

Urea appears to be a key intermediate of important prebiotic synthetic pathways. Concentrated pools of urea likely existed on the surface of the early Earth, as urea is synthesized in significant quantities from hydrogen cyanide or cyanamide (widely accepted prebiotic molecules), it has extremely high water solubility, and it can concentrate to form eutectics from aqueous solutions. We propose a model for the origin of a variety of canonical and non‐canonical nucleobases, including some known to form supramolecular assemblies that contain Watson‐Crick‐like base pairs.The dual nucleophilic‐electrophilic character of urea makes it an ideal precursor for the formation of nitrogenous heterocycles. We propose a model for the origin of a variety of canonical and noncanonical nucleobases, including some known to form supramolecular assemblies that contain Watson‐Crick‐like base pairs. These reactions involve urea condensation with other prebiotic molecules (e. g., malonic acid) that could be driven by environmental cycles (e. g., freezing/thawing, drying/wetting). The resulting heterocycle assemblies are compatible with the formation of nucleosides and, possibly, the chemical evolution of molecular precursors to RNA. We show that urea eutectics at moderate temperature represent a robust prebiotic source of nitrogenous heterocycles. The simplicity of these pathways, and their independence from specific or rare geological events, support the idea of urea being of fundamental importance to the prebiotic chemistry that gave rise to life on Earth. Pools of water enriched with urea would have been an efficient source for the formation of noncanonical pyrimidines. In the presence of aldose sugars, bases from these pools could react with the sugars through spontaneous glycosylation, ultimately concentrating de novo nucleosides through aggregation. We demonstrate how such a setting could lead to noncanonical nucleosides on a prebiotic Earth.