Supramolecular cage encapsulation as a versatile tool for the experimental quantification of aromatic stacking...

Area of Science:

• Supramolecular Chemistry
• Physical Organic Chemistry
• Chemical Physics

Background:

• Aromatic stacking interactions are ubiquitous in chemical and biological systems.
• Quantifying these interactions is essential for understanding molecular recognition and self-assembly.
• Existing studies present conflicting evidence regarding the dominant forces governing aromatic interactions.

Purpose of the Study:

• To investigate the role of substituents in modulating aromatic stacking interactions.
• To differentiate between local electrostatic contacts and substituent dipole interactions.
• To provide a quantitative understanding of the forces governing aromatic stacking.

Main Methods:

• Development of a supramolecular cage to control the geometry of stacked aromatic carboxylates.
• Utilized Chemical Double Mutant Cycles (DMCs) to measure interaction energies.
• Systematically varied substituents on aromatic rings (NMe₂, OMe, Me, Cl, NO₂).

Main Results:

• Attractive interactions observed with electron-withdrawing nitro substituents (-2.8 kJ mol⁻¹).
• Repulsive interactions observed with electron-donating dimethylamino substituents (+2.0 kJ mol⁻¹).
• Demonstrated that π-electron repulsion/attraction is a key factor, influenced by substituents.

Conclusions:

• Aromatic stacking interactions are predominantly governed by short-range electrostatic contacts.
• Substituent effects on π-electron density play a more significant role than substituent dipole moments.
• Findings clarify the fundamental nature of aromatic interactions in molecular systems.