Radical pathways for the formation of non-canonical nucleobases in prebiotic environments

Due to the inability of canonical nucleobases (adenine, uracil, guanine and cytosine) to spontaneously form ribonucleosides and base pairs in free form in solution, RNA is believed to be preceded by a primitive information polymer (preRNA). The preRNA is proposed to contain non-canonical, heterocyclic bases that possess the above-mentioned capabilities. An extensive search for such candidate heterocycles has recently revealed that barbituric acid (BA), melamine (MM) and 2,4,6-triaminopyrimidine (TAP) have the capability to spontaneously form ribonucleosides and supramolecular assemblies that are held by Watson-Crick type hydrogen-bonded base pairs involving BA, MM, TAP and cyanuric acid (CA) heterocycles. However, despite this evidence, the prebiotic formation pathways of these heterocycles have not been fully explored. Further, for these heterocycles to interact and assemble into informational polymers under prebiotic conditions, it is expected that they should have formed in the proximity of each other. In this context, the present work employs density functional theory to propose the associated radical based formation pathways starting from cyanamide. Our pathways suggest that cyanamide, its derivatives (malonic acid and urea) and malononitrile can form BA, MM, CA and TAP in the presence of ammonia and hydroxyl radicals. In addition to originating from a common precursor, similarities in the highest reaction barriers (13 to 20 kcal mol^-1) obtained for these pathways suggest that these heterocycles may likely form under similar conditions. Specifically, these pathways are relevant to high energy events such as meteoritic impact during the late heavy bombardment period on the early earth, which would have created conditions where radicals might have formed in reasonable concentrations. Overall, the present study emphasizes the importance of cyanamide in prebiotic heterocycle formation.