Strong positive allosteric cooperativity in ternary complexes based on hydrogen-bonded aromatic amide macrocycles

Area of Science:

• Supramolecular Chemistry
• Organic Synthesis
• Crystal Engineering

Background:

• Hydrogen-bonded aromatic amides form macrocyclic structures with unique binding properties.
• Previous studies on smaller cycloaramides indicated negative cooperativity in guest binding.
• Understanding macrocycle conformation and cooperativity is crucial for designing advanced molecular architectures.

Purpose of the Study:

• To synthesize novel, larger hydrogen-bonded aromatic amide macrocycles.
• To determine the single crystal structure and conformational properties of these new macrocycles.
• To investigate the allosteric cooperativity in guest binding compared to smaller analogs.

Main Methods:

• Synthesis of three new eight-residue aromatic amide macrocycles.
• Single crystal X-ray diffraction analysis to determine molecular structure.
• Binding studies to assess allosteric cooperativity in ternary complex formation.

Main Results:

• Successful synthesis of three novel eight-residue macrocycles.
• Obtained the first single crystal structure of this class of larger macrocycles, revealing a saddle-like conformation.
• Observed strong positive allosteric cooperativity in ternary complex formation, contrasting with negative cooperativity in smaller cyclo[6]aramides.

Conclusions:

• The synthesized larger macrocycles possess a unique saddle conformation.
• Strong positive allosteric cooperativity in these macrocycles presents a new paradigm for molecular recognition.
• These findings open possibilities for constructing advanced mechanically interlocked molecules using these larger macrocycles.