Attracting Opposites: Promiscuous Ion-π Binding in the Nucleobases

Ion-π interactions between the face of a molecular π-system and a cation or anion are among the strongest non-covalent interactions (NCIs) known, with applications throughout biology, chemistry, and physics. In this work [1], we perform a detailed theoretical case study of ion-π interactions with the DNA/RNA nucleobases, demonstrating that these π-systems are promiscuous ion-π binders with the versatility to bind both cations (Li+/Na+) and anions (F-/Cl-). Using a novel SAPT-based energy decomposition analysis, we explore the physicochemical driving forces underlying cation- and anion-π complexes, and uncover the role played by charge penetration effects in governing the non-trivial and often counterintuitive electrostatics in anion-π systems. In doing so, we present a unified view of these rather distinct NCIs, in which the stability of both cation- and anion-π complexes are stabilized by an essentially ring-independent potential that can only be overcome by substantially unfavorable electrostatics. Interestingly, this analysis demonstrates that π-systems have an inherent propensity to bind both cations and anions, thereby implying that promiscuous ion-π binding should be quite common in nature.
[1] J Phys Chem A 124, 4128 (2020).