Small-Molecule Organocatalysis Facilitates In Situ Nucleotide Activation and RNA Copying

A key challenge inorigin-of-life research is the identificationof plausible conditions that facilitate multiple steps along the pathwayfrom chemistry to biology. The incompatibility of nucleotide activationchemistry and nonenzymatic template-directed RNA copying has hinderedattempts to define such a pathway. Here, we show that adding heteroaromaticsmall molecules to the reaction network facilitates in situ nucleotidephosphate activation under conditions compatible with RNA copying,allowing both reactions to take place in the same mixture. This isachieved using Passerini-type phosphate activation in concert withnucleophilic organocatalysts that intercept high-energy reactive intermediates;this sequence ultimately affords 5 & PRIME;,5 & PRIME;-imidazolium-bridgeddinucleotides the active species in template-directed RNA polymerization.Our results suggest that mixtures of prebiotically relevant heteroaromaticsmall molecules could have played a key role in the transition fromchemistry to biology.

Automated summary

The challenge in origin-of-life research is to find conditions that facilitate the transition from chemistry to biology. The incompatibility of nucleotide activation chemistry and nonenzymatic template-directed RNA copying has hindered the identification of such conditions. However, this study shows that adding heteroaromatic molecules to the reaction network allows for nucleotide activation and RNA copying to occur simultaneously, suggesting the potential role of prebiotic heteroaromatic molecules in the transition from chemistry to biology.