The Unexpected Base‐Pairing Behavior of Cyanuric Acid in RNA and Ribose versus Cyanuric Acid Induced Helicene Assembly of Nucleic Acids: Implications for the Pre‐RNA Paradigm

The cyanuric acid (CA) heterocycle forms supramolecular structures with adenine nucleobases/nucleosides and oligonucleotides, leading to speculation that they can act as forerunners to RNA. Herein, the assembly behavior of RNA containing CA and CA–ribose nucleoside was studied. Contrary to previous reports, CA in RNA and the CA‐ribonucleoside resulted in destabilization of supramolecular assemblies, which led to a reevaluation of the CA–adenine hexameric rosette structure. An unprecedented noncovalent supramolecular helicene structure is proposed to account for the striking difference in behavior, which has implications for novel paradigms for reorganizing the structures of nucleic acids, the synthesis of long helicenes, and pre‐RNA world paradigms. The results caution against extrapolating the self‐assembly behavior of individual heterocycles from the level of monomers to oligomers because the base‐paring properties of (non‐)canonical nucleobases are impacted by the type of oligomeric backbone to which they are attached. Back to basics: An unprecedented hydrogen‐bonded helicene model is proposed to explain the surprising loss of base‐pairing properties of the cyanuric acid heterocycle upon being tagged with ribonucleoside and oligonucleotide. The results have wide‐ranging implications for creating novel nucleic acid structures, the synthesis of long helicenes, and the role of small molecules as pre‐RNA.