Spatial mismatch, non-additive binding energies and selectivity in supramolecular complexes.

Area of Science:

• Supramolecular Chemistry
• Chemical Biology
• Molecular Recognition

Background:

• Spatial arrangement of binding sites is crucial for molecular interactions.
• Understanding receptor-ligand spatial mismatch is key to designing effective supramolecular complexes.
• Existing models often overlook the impact of spatial arrangement on binding affinity and selectivity.

Purpose of the Study:

• To illustrate the consequences of spatial mismatch on affinity and selectivity in supramolecular complexes.
• To investigate how flexibility and binding site arrangement influence binding characteristics.
• To explore strategies for mitigating negative effects of spatial mismatch.

Main Methods:

• Analysis of diverse supramolecular complex examples, including cyclodextrins and biopolymers.
• Evaluation of non-covalent forces and their dependence on conformational rigidity and flexibility.
• Examination of binding energy additivity and affinity-selectivity correlations in multi-site interactions.

Main Results:

• Spatial mismatch significantly alters affinity and selectivity, especially in conformationally rigid systems.
• Loss of binding energy additivity and affinity-selectivity correlation occurs with partial mismatch in multi-site complexes.
• Cyclodextrin complexes and biopolymer associations demonstrate varied responses to spatial arrangement, impacting binding modes and preferences.

Conclusions:

• Spatial mismatch poses significant challenges for achieving desired affinity and selectivity in supramolecular complexes.
• Flexible linkers can be strategically employed to decouple affinity and selectivity, improving binding outcomes.
• Design principles for supramolecular systems must account for spatial arrangement to optimize molecular recognition.