Prebiotically Plausible Synthesis of N-Cyanoimidazole for Phosphate Activation and Templated RNA Ligation

Phosphate activation is a key step in the transition from mononucleotides and short oligonucleotides to polynucleotides by primer-extension and/or ligation. Prebiotically plausible phosphate activating reagents have remained elusive, with potential candidates limited by either poor reactivity or uncertain prebiotic provenance. Here we report a prebiotically plausible synthesis of N-cyanoimidazole, a known and efficient phosphate activating reagent, by reaction of thiocyanogen with imidazole. We further demonstrate that N-cyanoimidazole can effect mononucleotide activation and highly efficient RNA ligation in nicked duplexes with a range of oligomers including trimers and dimers.