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

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.