Solubility of Hydrophobes into Macrocyclic Hosts

Area of Science:

• Supramolecular Chemistry
• Computational Chemistry
• Physical Chemistry

Background:

• Macrocyclic molecules exhibit selective solute absorption, a cornerstone of supramolecular chemistry.
• The precise molecular determinants governing host-guest complexation, particularly guest solubility, remain incompletely understood.
• Rigorous thermodynamic analysis is crucial for elucidating the driving forces behind host-guest interactions.

Purpose of the Study:

• To quantitatively assess the energetic and entropic contributions to noble gas inclusion within macrocyclic hosts.
• To investigate the influence of host structure and dynamics on guest solubility and binding.
• To explore the nature of free-energy barriers encountered during host-guest complexation.

Main Methods:

• Employed molecular dynamics simulations to model the inclusion process.
• Utilized the potential distribution theorem to calculate solute-solvent energetic and entropic contributions.
• Examined noble gas inclusion in cucurbit[5]uril, cucurbit[6]uril, and α-cyclodextrin.

Main Results:

• Both solute-solvent energy and entropy favor noble gas inclusion in all host-guest systems studied.
• The energetic contribution was found to be the dominant factor driving inclusion.
• Host-specific differences in interior drying frequency correlate with portal water and framework flexibility, impacting entropic contributions.

Conclusions:

• Energetic factors play a predominant role in the thermodynamic favorability of noble gas inclusion within macrocycles.
• Host structural features, such as portal water and flexibility, modulate entropic contributions to binding.
• Macrocyclic hosts exhibit diverse binding mechanisms, characterized by varying free-energy barrier profiles.