Mapping the internal recognition surface of an octanuclear coordination cage using guest libraries

Area of Science:

• Supramolecular Chemistry
• Coordination Chemistry
• Host-Guest Chemistry

Background:

• Octanuclear cubic coordination cages are explored for guest encapsulation.
• Understanding guest binding criteria is crucial for designing selective host molecules.

Purpose of the Study:

• To establish size and shape criteria for guest binding within an octanuclear cubic coordination cage.
• To quantify guest binding affinity using a novel fluorescence displacement assay.

Main Methods:

• Utilized a fluorescence displacement assay to measure guest binding.
• Investigated a series of aliphatic cyclic ketones (C5-C11) and C10 ketones with varying shapes.
• Determined binding free energy (ΔG) and association constants (K).
• Obtained a crystal structure of the cage-cycloundecanone complex.

Main Results:

• A linear relationship exists between ΔG and surface area for cyclic ketones (C5-C11), with binding affinity increasing with size up to cycloundecanone (K = 1.2 × 10^6 M⁻¹).
• Larger cyclic ketones (C12-C13) showed decreased binding affinity due to size limitations.
• For C10 ketones of similar size but different shapes, binding affinity was sensitive to shape complementarity, not surface area.
• Preorganized cyclic ketones exhibited higher association constants (10⁴–10⁵ M⁻¹) than flexible linear ketones, which did not bind.
• Crystal structure revealed specific interactions, including weak hydrogen bonds and surface contacts, between the cage and cycloundecanone.

Conclusions:

• Guest binding is governed by both size and shape complementarity within the coordination cage.
• Hydrophobic desolvation plays a significant role in binding affinity.
• Shape complementarity becomes critical when guests approach the cavity's volume limit.
• The cage demonstrates selective binding, favoring preorganized cyclic guests.