Ultra-Tight Host-Guest Binding with Exceptionally Strong Positive Cooperativity
Thomas A Sobiech1, Yulong Zhong1, Daniel P Miller2
1Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA.
Angewandte Chemie (International Ed. in English)
|October 19, 2022
Summary
This study demonstrates a novel macrocycle host-guest system exhibiting exceptionally strong positive cooperativity. This supramolecular system achieves high binding affinities, offering a tunable platform for molecular interactions and assembly.
Area of Science:
- Supramolecular Chemistry
- Host-Guest Chemistry
- Organic Chemistry
Background:
- Cooperativity is crucial for molecular recognition and self-assembly processes.
- Synthetic host-guest systems are vital for understanding molecular interactions.
- Macrocyclic compounds offer unique binding capabilities.
Purpose of the Study:
- To investigate the binding behavior of a rigid aromatic oligoamide macrocycle with DABCO-based cationic guests.
- To quantify the cooperativity and affinity in this host-guest system.
- To explore the potential of this system for studying molecular interactions and supramolecular assembly.
Main Methods:
- Isothermal titration calorimetry (ITC) for binding affinity and cooperativity.
- Mass spectrometry and Nuclear Magnetic Resonance (NMR) for corroboration.
- Computational studies to elucidate binding mechanisms.
Main Results:
- A 2:1 host-guest complex formed with high affinities (Ktotal ≈ 10^13 M^-2) in DMF.
- Exceptionally strong positive cooperativity was observed, with large interaction factors.
- Guest-induced macrocycle stacking and stabilization by guest alkyl chains were identified as key drivers.
Conclusions:
- The studied host-guest system exhibits extraordinary positive cooperativity, leading to tight binding.
- This system serves as a tunable platform for fundamental studies of molecular interactions.
- The findings enable the construction of stable supramolecular assemblies.
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