Aromatic interactions with heterocycles in water

Area of Science:

• Supramolecular Chemistry
• Organic Chemistry
• Physical Chemistry

Background:

• Supramolecular complexes offer a platform to study functional group interactions and solvation effects.
• Understanding these interactions is crucial for designing selective molecular recognition systems.

Purpose of the Study:

• To dissect and quantify the contributions of aromatic interactions to the stability of calix[4]pyrrole-heterocycle complexes.
• To investigate the influence of solvent (water vs. chloroform) on these aromatic interactions.
• To elucidate the role of heteroatoms within aromatic guests on binding affinity.

Main Methods:

• Synthesis of four distinct calix[4]pyrrole receptors and eleven pyridine N-oxide guests.
• Formation of 1:1 supramolecular complexes.
• Characterization using proton nuclear magnetic resonance (¹H NMR) spectroscopy.
• Quantification of interaction energies via chemical double mutant cycles.

Main Results:

• Complex structures are stabilized by four hydrogen bonds, fixing aromatic interaction geometries.
• In chloroform, aromatic interactions are similar to phenyl groups, with heteroatom position causing repulsion up to 8 kJ/mol.
• In water, heterocycle interactions are more favorable (up to 12 kJ/mol), correlating with hydrophobicity for non-polar heterocycles.
• Polar nitrogen atoms in guests form stabilizing water hydrogen bonds (approx. 15 kJ/mol).

Conclusions:

• Solvation plays a complex role in molecular recognition in water.
• Aromatic interactions are modulated by solvent polarity and the specific location of heteroatoms.
• Calix[4]pyrrole-guest complexes provide a robust model for studying fundamental binding principles.