Comprehensive Characterization of the Self-Folding Cavitand Dynamics.

Area of Science:

• Supramolecular Chemistry
• Computational Chemistry
• Chemical Physics

Background:

• Cavitand receptors, derived from resorcin[4]arenes, exhibit complex conformational dynamics.
• Understanding these dynamics is crucial for designing effective synthetic host-guest systems.

Purpose of the Study:

• To comprehensively characterize the conformational equilibria and guest exchange of a self-folding cavitand receptor.
• To develop and validate a multi-timescale simulation strategy for exploring fluxional behavior.

Main Methods:

• Utilized conventional and accelerated molecular dynamics (MD and aMD) simulations.
• Employed 1H Nuclear Magnetic Resonance (NMR) spectroscopy, specifically 1H EXSY experiments.
• Developed a multi-timescale strategy to capture events from nanoseconds to seconds.

Main Results:

• Reconstructed the folding/unfolding process, including partially open intermediates.
• Observed guest departure occurring at various folding stages.
• aMD simulations, after reweighing, accurately predicted kinetic barriers matching experimental NMR data.

Conclusions:

• Provided the first detailed characterization of cavitand receptor dynamics.
• Demonstrated the utility of aMD simulations for studying high-energy barrier processes in host-guest systems.
• The developed approach serves as a valuable tool for the rational design of synthetic host-guest systems.