Guest Controlled Nonmonotonic Deep Cavity Cavitand Assembly State Switching.

Area of Science:

• Supramolecular Chemistry
• Computational Chemistry
• Molecular Recognition

Background:

• Octa-acid (OA) and tetra-endo-methyl octa-acid (TEMOA) are water-soluble cavitands with deep, nonpolar pockets for binding guests like n-alkanes.
• OA forms distinct host/guest complexes (1:1, 2:2, 2:1) with increasing alkane length.
• TEMOA, with added methyl groups at the pocket opening, exhibits a more complex, nonmonotonic assembly progression.

Purpose of the Study:

• To elucidate the molecular and thermodynamic factors differentiating the assembly stoichiometries of OA and TEMOA.
• To utilize molecular simulations to understand the impact of structural modifications on supramolecular complex formation.
• To validate simulation methods against experimental observations of host-guest complexation.

Main Methods:

• Systematic molecular simulation studies were performed.
• Potentials of mean force (PMF) were calculated using umbrella sampling to determine association free energies.
• A reaction network model was employed to predict equilibrium assembly distributions based on calculated free energies.

Main Results:

• The simulations accurately reproduced the experimentally observed assembly trends for both OA and TEMOA.
• TEMOA's endo-methyl groups were identified as key factors constricting the pocket opening.
• This constriction limits guest conformations and alters the balance between monomeric and dimeric complexes.

Conclusions:

• Molecular simulations effectively interpret the influence of minor chemical modifications on supramolecular assembly.
• The study highlights the role of pocket opening dynamics in dictating complex stoichiometry.
• These simulation approaches can aid in the rational design of novel supramolecular hosts.