U ncatalyzed Guanosine Phosphorylation under Potentially Prebiotic Conditions

ABSTRACT The phosphorylation of nucleosides and their subsequent polymerization are key issues in the study of the Origins of Life. How these chemical processes took place on primitive Earth remains a puzzle. In this study, we examine the thermal phosphorylation of guanosine in water under wet‐dry conditions and in the presence of sodium pyrophosphate, without the use of condensing agents or chemical catalysts. Phosphorylation occurs selectively, yielding cyclic guanosine monophosphates and cyclic guanosine polyphosphates bearing polyphosphate side chains of different lengths. Interestingly, this reaction mimics the phosphorylation of nucleosides by purine nucleotide pyrophosphotransferase enzymes in present‐day organisms. The fact that the phosphorylation reaction is not thermodynamically spontaneous in aqueous solutions, even at moderate water activities, highlights the efficacy of the reported procedure. These observations outline a plausible prebiotic scenario for the formation of building‐blocks of the pre‐genetic apparatus involving a simple phosphorylating reagent and wet‐dry cycles.