Generation of RNA Molecules by a Base‐Catalysed Click‐Like Reaction

The problem of the abiotic origin of RNA from prebiotically plausible compounds remains unsolved. As a potential partial solution, we report the spontaneous polymerization of 3′,5′‐cyclic GMP in water, in formamide, in dimethylformamide, and (in water) in the presence of a Brønsted base such as 1,8‐diazabicycloundec‐7‐ene. The reaction is untemplated, does not require enzymatic activities, is thermodynamically favoured and selectively yields 3′,5′‐bonded ribopolymers containing as many as 25 nucleotides. We propose a reaction pathway on the basis of 1) the measured stacking of the 3′,5′‐cyclic monomers, 2) the activation by Brønsted bases, 3) the determination (by MALDI‐TOF mass spectrometry, by 31 P NMR, and by specific ribonucleases) of the molecular species produced. The reaction pathway has several of the attributes of a click‐like reaction.