Exploring the Influence of Intermolecular Interactions in Prebiotic Chemistry Using Laser Spectroscopy and Calculations

One of the most fascinating questions in chemistry is why nature chose CGAT as the alphabet of life. Very likely, such selection was the result of multiple factors and a long period of refinement. Here, we explore how the intermolecular interactions influenced such process, by characterizing the formation of dimers between adenine, theobromine and 4‐aminopyrimidine. Using a combination of mass‐resolved excitation spectroscopy and DFT calculations, we determined the structure of adenine‐theobromine and 4‐aminopyrimidine‐theobromine dimers. The binding energy of these dimers is very close to the canonical adenine‐thymine nucleobases. Likewise, the dimers are able to adopt Watson‐Crick conformations. These findings seem to indicate that there were many options available to build the first versions of the informational polymers, which also had to compete with other molecules, such as 4‐aminopyrimidine, which does not have a valid attaching point for a saccharide. For some reason, nature did not select the most strongly‐bonded partners or if it did, such proto‐bases were later replaced by the nowadays canonical CGAT. Exploiting the synergy between laser spectroscopy and calculations, the interaction potential energy surfaces of the dimers between adenine and 4‐aminopyrimidine with theobromine have been explored. Both systems form stable aggregates with two strong hydrogen bonds, with binding energy values resembling the Watson‐Crick analogue interactions. An energetic comparison suggests how intermolecular interactions influenced the evolutionary sequence.