Four faces of the interaction between ions and aromatic rings

Area of Science:

• Computational Chemistry
• Biomolecular Interactions
• Quantum Chemistry

Background:

• Non-covalent ion-aromatic interactions stabilize macromolecular complexes, particularly in proteins with aromatic residues and charged amino acids.
• Four types of attractive interactions (perpendicular cation-π [CP⊥], co-planar cation-π [CP∥], perpendicular anion-π [AP⊥], and co-planar anion-π [AP∥]) are proposed based on ion position relative to the aromatic ring.

Purpose of the Study:

• To systematically investigate and quantify the four types of ion-aromatic-ring interactions using high-level quantum chemical methods.
• To provide benchmark interaction energies for model systems representing electron-rich and electron-deficient aromatic systems.
• To evaluate the performance of density functional theory (DFT) methods for characterizing these interactions in large biomolecules.

Main Methods:

• Utilized focal-point analysis (FPA), a benchmark-quality quantum chemical technique, to calculate interaction energies.
• Employed model systems: X− + C6H6, M+ + C6H6, X− + C6F6, and M+ + C6F6, with various ions (X−, M+) and aromatic rings (C6H6, C6F6).
• Performed natural bond orbital (NBO) analysis for qualitative understanding and tested DFT methods (B3LYP, BHandHLYP, M06-2X) against FPA results.

Main Results:

• Calculations revealed significant stabilization from ion-aromatic interactions.
• The interaction energy order was determined as CP⊥ (23–37 kcal mol−1) > AP⊥ (14–21 kcal mol−1) > CP∥ (9–22 kcal mol−1) > AP∥ (6–16 kcal mol−1).
• The M06-2X DFT functional demonstrated the best performance among the tested methods for approximating FPA benchmarks.

Conclusions:

• Ion-aromatic-ring interactions significantly stabilize biomolecular structures.
• The relative strengths of the four interaction types were quantitatively established.
• The M06-2X functional is recommended for future quantum chemical studies of ion-aromatic interactions in complex biomolecules.