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 Bronsted 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 Bronsted bases, 3) the determination (by MALDI-TOF mass spectrometry, by 31P NMR, and by specific ribonucleases) of the molecular species produced. The reaction pathway has several of the attributes of a click-like reaction.