Supramolecular polymers have a practical impact on the healthcare field as they can act as scaffolds to repair parts of organs such as the brain or heart. In addition, they can provide insight into theories relating to the origins of life. For instance, the hypothesis that RNA played a more important role in early biology, the RNA World hypothesis, would be strengthened if there were a way to show the spontaneous formation of RNA-like polymers from monomer units. However, the natural nucleobases do not assemble at the monomer level, nor do they form nucleosides readily with ribose, leading some to speculate that the first nucleobases may have been different from the ones used in biology today. This conundrum encouraged us to begin looking for alternative nucleobases that are able to self-assemble into polymers capable of storing information. Our lab has recently demonstrated that a modified 2,4,6-triaminopyrimidine (TAP) will assemble with cyanuric acid (CA) in water through interactions that are analogous to those between complementary nucleobases found in DNA and RNA. When TAP is modified at one of its three faces, it can pair through specific hydrogen bonding with CA on two of its faces, forming rosette structures. These rosettes self-assemble to form extremely long structures through the stacking of tens of thousands of rosettes. In this study we are investigating prebiotically relevant syntheses of TAP nucleosides. Using chromatography techniques and nuclear magnetic resonance we found that the unmodified TAP with D-ribose formed nucleosides in 60% yields with the major product (20%) being a C-nucleoside 5-β-ribofuranosyl-2,4,6-triaminoprymidine or TARC. TARC forms hydrogels with CA, both in the crude reaction and after purification, indicative of the formation of supramolecular polymers out of a complex mixture. The results of this study provide support for the possibility of pre-RNA molecules.

Cations are essential for ribonucleic acids (RNA), as they neutralize the negatively charged phosphate backbone. Divalent metals play important roles in the folding and function of RNA. The relationship between RNA and divalent cations magnesium (Mg(II)) and iron (Fe(II)) has been investigated. Mg(II) is involved in tertiary interactions of many large RNAs, and necessary for ribozyme activity. The influence of Mg(II) on RNA secondary and tertiary structure is investigated experimentally. Mg(II) binding to A-form RNA is accompanied by changes in CD spectra, indicating that Mg-RNA interactions influence the helical structure of RNA duplexes and helical regions of unfolded RNAs. Quantum mechanics calculations are used to probe the energetics of Mg(II)-chelation with phosphate oxygen atoms of nucleic acids. We identify the specific forces that contribute to stability of Mg(II)-chelation complexes in RNA. Fe(II) can serve as a substitute for Mg(II) in RNA folding and function. Fe(II) was abundant on early earth, it is plausible that RNA folding and function was mediated by Fe(II) instead of, or in combination with, Mg(II) in the anoxic environment of early earth. We have investigated oxidoreductase catalytic activity observed in RNA when in combination with Fe(II). This activity, only observed in the presence of Fe(II) and absence of Mg(II)appears to be a resurrection of ancient RNA capabilities that were extinguished upon the depletion of Fe(II) from the environment during the rise of oxygen after the great oxidation event. Finally, metal-ion based cleavage of RNA is used to identify the binding sites of Mg(II) and Fe(II). We observe that both metals cleave RNA in similar positions, providing further support for Fe(II) as a substitute for Mg(II) in RNA.