Self-Catalytic Mechanism of Prebiotic Reactions: From Formamide to Pyrimidines.

The search for prebiotic chemical pathways to biologically relevant molecules and their precursors has been a longstanding puzzle. On the basis of our previous experimental study, a general scheme for prebiotic reaction routes from formamide to different precursors and pyrimidine bases, namely, cytosine, uracil, 5-methylcytosine, thymine, isocytosine, and 2,4-diaminopyrimidine, is proposed. All required precursors, such as hydrogen cyanide, ammonia, water, formic acid, isocyanic acid, formyl cyanide, cyanamide, urea, 2-aminoacetonitrile, guanidine, formaldehyde, cyanovinylalcohol, and cyanoacetaldehyde, needed in the reactions are obtained by decomposition of the starting compound, namely, formamide. In these reactions, formamide and its tautomer, formimidic acid, as well as formic acid, play the role of a proton-carrying catalyst. A diverse reactivity landscape was revealed within just a few steps of those of these simple molecules. Reaction pathways to cytosine and uracil were discovered, involving lower activation energies and fewer reaction steps compared with those of proposed alternatives. Accounting for formamide-catalyzed reactions qualitatively affects the interpretation of the reaction kinetics.