Simulation optimization of spherical non-polar guest recognition by deep-cavity cavitands

Area of Science:

• Supramolecular Chemistry
• Computational Chemistry
• Host-Guest Chemistry

Background:

• Biomimetic deep-cavity cavitands exhibit selective binding of non-polar guests.
• Adamantane derivatives show strong host binding within octa-acid cavitands.
• Understanding guest properties is key to optimizing host-guest complexation.

Purpose of the Study:

• To investigate the influence of guest size and attractive interactions on binding within octa-acid cavitands.
• To explore water-mediated interactions in host-guest complex formation.
• To identify optimal guest characteristics for strong 1:1 complexation.

Main Methods:

• Molecular simulations were used to study cavitand-guest interactions in water.
• Lennard-Jones potentials modeled simple guests of varying diameter and well-depth.
• Potential-of-mean force calculations determined binding free energies.

Main Results:

• Hydrated methane preferentially occupied the cavitand pocket but showed dynamic exchange with bulk solution.
• Hydrophobic guest binding strength increased with size up to adamantane-like dimensions.
• Guests larger than adamantane exhibited less favorable binding, shifting to the cavitand portal.
• Increasing guest attractive well-depth lowered binding free energy but did not alter optimal guest size.

Conclusions:

• Adamantane represents an optimal guest size for strong binding with octa-acid cavitands.
• Guest size is a primary determinant of binding affinity, more so than attractive interactions.
• The study provides insights into designing guests for enhanced encapsulation by deep-cavity cavitands.