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.

Cyanuric acid heterocycle (CA) forms supramolecular structures with adenine nucleobases/nucleosides and oligonucleotides leading to speculation that they can act as forerunners to RNA. Herein, we studied the assembly behavior of RNA containing CA and CA-ribose nucleoside. Contrary to previous reports, CA in RNA, and as the ribonucleoside, leads to destabilization of supramolecular assemblies, which led to reevaluation of the CA-adenine hexameric rosette structure. We propose an unprecedented non-covalent supramolecular helicene structure to account for the striking difference in behavior, which has implications for novel paradigms for reorganizing the structures of nucleic acids, 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 - since the base-paring properties of (non)canonical nucleobases are impacted by the type of oligomeric backbone to which they are attached.