Two Squares in a Barrel: An Axially Disubstituted Conformationally Rigid Aliphatic Binding Motif for Cucurbit[6]uril

Area of Science:

• Supramolecular Chemistry
• Host-Guest Chemistry
• Materials Science

Background:

• Supramolecular chemistry requires novel binding motifs for constructing sophisticated molecular devices like sensors and catalysts.
• Existing rigid, aliphatic binding motifs for cucurbiturils (CBs) that allow axial disubstitution are limited.

Purpose of the Study:

• To synthesize and characterize new rigid, aliphatic binding motifs for supramolecular host-guest complexation.
• To evaluate the binding properties of these novel motifs with cucurbit[6]uril (CB6), cucurbit[7]uril (CB7), and cyclodextrins (CDs).

Main Methods:

• Synthesis of three model guests featuring spiro[3.3]heptane and bicyclo[1.1.1]pentane cores with imidazolium and ammonium termini.
• Binding studies using Nuclear Magnetic Resonance (NMR) spectroscopy, titration calorimetry, mass spectrometry, and single-crystal X-ray diffraction.

Main Results:

• A bisimidazolio spiro[3.3]heptane guest formed inclusion complexes with CB6, CB7, and β-cyclodextrin with association constants (K) ranging from 1.4 × 10^2 to 1.2 × 10^12.
• A diammonio analogue exhibited enhanced binding with CB6 (K = 1.4 × 10^6) and CB7 (K = 3.8 × 10^12) due to less sterically hindering terminal groups.
• A bisimidazolio bicyclo[1.1.1]pentane guest showed highly selective and strong binding exclusively with CB7 (K = 1.1 × 10^11).

Conclusions:

• The newly developed spiro[3.3]heptane and bicyclo[1.1.1]pentane based binding motifs demonstrate significant potential for supramolecular chemistry.
• The high selectivity observed in complex formation with cucurbiturils and cyclodextrins suggests their utility in designing advanced multitopic supramolecular components.