“η⁶”‐Type anion–π in biomolecular recognition

Theoretical and compelling experimental evidence indicates that the interaction between an anion and an aromatic π system when the anion is directly above the ring face ("η(6)"-type anion-π), can be attractive. This may play an important role in the formation and recognition of biomolecular structures. We examined high-resolution structures of proteins and nucleic acids for the presence of "η(6)"-type anion-π. Though less frequent than its counterpart cation-π, "η(6)"-type anion-π is observed unambiguously, occurring in protein/nucleic acid loops and often involving conserved/coevolving sites in proteins, suggesting it plays an important role in macromolecular folding and function.