Controlling Swing Rates in Macrocyclic Molecular Mortise Hinges.

Area of Science:

• Supramolecular Chemistry
• Chemical Dynamics
• Structural Biology

Background:

• Macrocyclic compounds can form molecular hinges with dynamic properties.
• Understanding hinge motion is crucial for designing responsive molecular systems.

Purpose of the Study:

• To investigate the dynamic hinge motion in macrocyclic, mortise-type molecular hinges.
• To characterize the structural and energetic parameters governing this motion.

Main Methods:

• Variable temperature Nuclear Magnetic Resonance (NMR) spectroscopy was employed to observe hinge motion.
• X-ray crystallography and solution-state NMR were used to determine structures.
• Density Functional Theory (DFT) calculations were performed to elucidate the motion pathway.

Main Results:

• Dynamic hinge motion was observed, consistent with a folded-to-extended-to-folded enantiomeric state.
• Crystallographic data corroborated fully revolute hinge motion through chemical shift predictions.
• Steric congestion at the hinge axis significantly affects the rate of hinging.
• Free energies of activation (ΔG≠) were determined: 13.3±0.3 kcal/mol for glycine-containing macrocycle (1) and 16.3±0.3 kcal/mol for aminoisobutyric acid-containing macrocycle (2).
• The energy barrier for hinging was largely solvent-independent.

Conclusions:

• The observed hinge motion is driven by the disruption of an intramolecular hydrogen bond network.
• DFT calculations provide a detailed pathway for the observed hinge motion.
• The study provides insights into the design principles for controlling molecular hinge dynamics.