Base-pairing of uracil and 2,6-diaminopurine: from cocrystals to photoreactivity

22 June 2023, Version 1


The information molecule of the first life on Earth is presumably ribonucleic acid (RNA). RNA is a polymer built out of four canonical nucleobases: adenine (A), uracil (U), guanine (G), and cytosine (C). However, it remains unclear how canonical nucleobases got selected from the hundreds available in nature. Here, we show that the non-canonical nucleobase 2,6-diaminopurine (D) base pairs with U in water and the solid state without the need to be attached to the ribose-phosphate backbone. Depending on the temperature and water availability in the system, D and U assemble in thermodynamically stable hydrated and anhydrated D-U base-paired cocrystals. Structural studies show that the water molecules contribute favorably to the stabilization energies in D-U cocrystal hydrate due to the role of water in forming inter-layer hydrogen bonds. In the anhydrate cocrystal form, D and U molecules exhibit advantageous homomeric stacking interactions and hydrogen bonding. Under UV irradiation, an aqueous solution of D-U base-pair undergoes photochemical degradation, while a pure aqueous solution of U does not, thus demonstrating that base-pairing alters the photostability of U. To understand this decreased photostability of U, we model the main channel for U photodestruction, i.e., covalent photodimerization. Our simulations suggest that D may trigger the U photodimerization because of its ability to form hydrogen bonds with π-stacking dimers of U. Our results indicate that complementary base-pairing of D and U in prebiotic surface environments may have played a role in chemical evolution. In a broader context, supramolecular interactions between small biological building blocks may offer new insights into the origin of life.


Prebiotic chemistry
Chemical evolution
Electron diffraction
UV resonance Raman spectroscopy
Density functional theory
Synchrotron powder X-ray diffraction

Supplementary materials

Supplementary information
Supplementary information for the paper.


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