Additivity of substituent effects in aromatic stacking interactions

Area of Science:

• Chemistry
• Physical Chemistry
• Computational Chemistry

Background:

• Aromatic stacking interactions are fundamental in molecular recognition and materials science.
• Understanding substituent effects (SEs) is key to controlling these interactions.
• The additivity of SEs in aromatic stacking has remained experimentally underexplored.

Purpose of the Study:

• To experimentally validate the additivity of electrostatic substituent effects (SEs) in aromatic stacking interactions.
• To quantify the impact of various substituents on the strength of aromatic stacking.
• To assess the predictive capability of additive SE models.

Main Methods:

• Utilized a small molecule model system with offset face-to-face aromatic stacking geometry.
• Measured intramolecular interactions via conformational equilibrium shifts in molecular torsional balances.
• Quantified stacking interaction strengths for 21 substituted and 21 control systems in chloroform.

Main Results:

• Observed stability trends strongly supported the additivity of electrostatic SEs.
• Additive SE models accurately predicted SEs within ±0.01 to ±0.02 kcal/mol.
• Results align with Wheeler and Houk's direct SE model, though indirect models show similar additivity for small substituent numbers.

Conclusions:

• Electrostatic substituent effects in aromatic stacking interactions are demonstrably additive.
• Additive models offer accurate predictions, facilitating rational molecular design.
• This work provides a foundation for optimizing systems reliant on aromatic stacking.