Albany 2013: Book of Abstracts

category image Albany 2013
Conversation 18
June 11-15 2013
©Adenine Press (2012)

Supramolecular Polymerization of Nucleobase-like Monomers in Water

Elucidating the physiochemical principles that govern molecular self-assembly is of great importance for understanding biological systems and may provide insight into the emergence of the earliest macromolecules of life, an important challenge facing the RNA World hypothesis. Self-assembly results from a delicate balance between multiple noncovalent interactions and solvent effects, but achieving efficient self-assembly in aqueous solution with synthetic molecules has proven particularly challenging. Here we demonstrate how two physical properties – monomer solubility and large hydrophobic surfaces of intermediate structures – are key elements to achieving supramolecular polymers in aqueous solution (Cafferty et al., 2013). Applying these two principles, we report the highly cooperative self-assembly of two weakly interacting, low molecular weight monomers [cyanuric acid (CA) and a modified triaminopyrimidine (TAPAS)] into a water-soluble supramolecular assembly (see scheme below). The observed equilibrium between only two appreciably populated states – free monomers and supramolecular assemblies – is in excellent agreement with values previously determined for the free energy of hydrogen bonding (Klostermeier & Millar, 2002), π-π stacking (Frier et al., 1985) and the calculated free energy penalty for the solvation of hydrophobic structures in water (Chandler 2005). The similarity of the molecules used in this study to the nucleobases found in contemporary nucleic acids and the demonstration that these monomer assemble while the natural nucleobases do not, suggests that the first informational polymers may have emerge from a similar self-assembly process if the nucleobases were different then they are today (Hud et al., 2013).


This research has been supported by NSF and the NASA Astrobiology Program under the NSF Center for Chemical Evolution [CHE-1004570], and Consejo Superior de Investigaciones Cientifíficas (CSIC) [MEC,SAB2010-0163].


    Cafferty B.J. et al., (2013) J. Am. Chem. Soc. 135, 2447–50
    Klostermeier D. &.Millar D. P. (2002). Biochemistry 41, 14095-102
    Frier S. M. et al. (1985). Biochemistry 24, 4533-39
    Chandler D. (2005). Nature 437, 640-7
    Hud N. V. et al. (2013) Chemistry & Biology, Submitted.

Isaac Gállego1
Brian J. Cafferty1
Michael C. Chen1
Katherine I. Farley1
Ramon Eritja2
Nicholas V. Hud1

1Department of Chemistry and Biochemistry
Parker H. Petit Institute for Bioengineering and Bioscience
Georgia Institute of Technology
Atlanta, Georgia 30332-0400, United States
2Institute for Research in Biomedicine
Parc Científic de Barcelona
Barcelona 08028, Spain

Ph: (404)385-1166