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

Abstract

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.

Keywords: aggregation; computational chemistry; laser spectroscopy; noncovalent interactions; prebiotic chemistry.

Scheme 1

Structure of theobromine, adenine, 4‐aminopyrimidine, thymine, and Watson‐Crick (WC) interactions for the canonical nucleobases.

Figure 1

The six most stable conformational isomers of theobromine‐adenine, together with their binding energy at 0 and 298 K. The binding energy value (kJ/mol) is the average of the two values computed at M06‐2X/6‐311+G(d,p) and B3LYP‐ED=GD3BJ/def2TZVP. The original values obtained with each theory level may be found in the Supporting Information. Hydrogen bond distances are those computed at the B3LYP‐ED=GD3BJ/def2TZVP level. Distances in Å.

Figure 2

The four most stable conformational isomers of theobromine‐4‐aminopyrimidine, together with their binding energy at 0 and 298 K. The binding energy value (kJ/mol) is the average of the two values computed at M06‐2X/6‐311+G(d,p) and B3LYP‐ED=GD3BJ/def2TZVP. The original values obtained with each theory level may be found in the Supporting Information. Hydrogen bond distances are given for B3LYP‐ED=GD3BJ/def2TZVP level. Distances in Å.

Figure 3

Comparison between the experimental spectrum of TB+A and the predictions for some selected computed structures. Experimental traces were recorded at a) 35,097 cm⁻¹ and b) 35,769 cm⁻¹ excitation wavelengths. The predictions for the two most stable structures fit very well with the experimental observation. The rest of the predicted spectra may be found in the Supporting Information.

Figure 4

Comparison between the experimental spectrum (recorded at 34,794 cm⁻¹) of TB+AP and the predictions for two computed structures, whose spectra are compatible with the experimental trace. The rest of the predicted spectra may be found in the Supporting Information.