Programmed Negative Allostery with Guest-Selected Rotamers Control Anion-Anion Complexes of Stackable Macrocycles

Area of Science:

• Supramolecular Chemistry
• Host-Guest Chemistry
• Chemical Biology

Background:

• Allosteric control is crucial for regulating molecular interactions and biological processes.
• Cyanostar macrocycles are known for their ability to bind guests.
• Understanding host-host interactions is key to designing functional molecular systems.

Purpose of the Study:

• To develop a rotamer-based strategy for achieving negative allostery.
• To control host-host interactions and product yield using anion complexation.
• To investigate the thermodynamic consequences of rotamer selection in macrocyclic systems.

Main Methods:

• Utilized a rotamer-based strategy for negative allosteric control.
• Employed anion complexation to induce guest-driven rotamer selection.
• Investigated the coassembly of anion dimers within cyanostar macrocycles.
• Quantified entropy changes associated with rotamer collapse.

Main Results:

• Successfully controlled host-host interactions and product yield via anion complexation.
• Demonstrated that coassembly of anion dimers drives selection of a specific rotamer.
• Showcased the outward orientation of steric groups in the selected rotamer.
• Observed destabilization of triply stacked macrocycles due to rotamer selection.
• Quantified a significant entropy penalty (ΔS) upon anion binding.

Conclusions:

• The rotamer-based strategy effectively enables negative allosteric control.
• Anion binding can precisely dictate macrocycle assembly and stability.
• Entropy plays a critical role in the thermodynamic driving force of these systems.
• This approach offers a new paradigm for controlling supramolecular systems.