Chemical and evolutionary reasons for the rarity of natural products containing nitrogen–nitrogen bonds (NN bonds) in life’s biochemical repertoire

Abstract Understanding the chemistry of life is a central motivation of biological research. This includes understanding why life does not use particular chemical structures. Compounds containing a bond between two nitrogen atoms (NN bonds) are relatively rare in the chemicals made by life. We quantify that rarity, and explore possible reasons for it. We find that the main limitation on the use of NN compounds in biochemistry could be the toxicity of NN bond containing metabolic intermediates in their biosynthesis. The potential toxicity of the final NN compound metabolites, the energy required for their synthesis, and differences in the functional benefit from their synthesis may play additional, minor roles in explaining the NN bond rarity in biochemistry. Our study adds to a growing body of work that aims to map and explain the constraints behind life choices in chemical space.