Catalysis of Template-Directed Nonenzymatic RNA Copying by Iron(II)

[Image: see text] The study of nonenzymatic template-directed RNA copying is the experimental basis for the search for chemistry and reaction conditions consistent with prebiotic RNA replication. The most effective model systems for RNA copying have to date required a high concentration of Mg(2+). Recently, Fe(2+), which was abundant on the prebiotic anoxic Earth, was shown to promote the folding of RNA in a manner similar to the case of Mg(2+), as a result of the two cations having similar interactions with phosphate groups. These observations raise the question of whether Fe(2+) could have promoted RNA copying on the prebiotic Earth. Here, we demonstrate that Fe(2+) is a better catalyst and promotes faster nonenzymatic RNA primer extension and ligation than Mg(2+) when using 2-methylimidazole activated nucleotides in slightly acidic to neutral pH solutions. Thus, it appears likely that Fe(2+) could have facilitated RNA replication and evolution in concert with other metal cations on the prebiotic Earth.