Sulfonatocalixarene Promotes Drug Assembly Based on Supramolecular Host•-Guest Complexation in Aqueous Solution

Area of Science:

• Supramolecular Chemistry
• Materials Science
• Medicinal Chemistry

Background:

• Host-guest complexation is key for designing functional supramolecular assemblies.
• Sulfonated macrocycles, like sulfonatocalixarenes (SCXn), are effective hosts in aqueous solutions.
• Drug molecules often require stable delivery systems for therapeutic applications.

Purpose of the Study:

• To design and characterize stable, nano-sized supramolecular assemblies using sulfonatocalixarenes and drug molecules.
• To investigate the driving forces and properties of these host-guest complexes in aqueous media.
• To explore the potential of these assemblies as functional materials, particularly their thermoresponsive behavior.

Main Methods:

• Host-guest complexation studies in aqueous solution using sulfonatocalixarenes (SCX4) and three drug molecules (doxepin, desipramine, promazine).
• Characterization of supramolecular complexation using fluorescence displacement titration and isothermal titration calorimetry.
• Analysis of interaction mechanisms, including ion-ion and C─H─π interactions.

Main Results:

• Formation of stable, nano-sized supramolecular assemblies between SCX4 and the drug molecules at low millimolar concentrations.
• Complexation is driven by ion-ion interactions between the negatively charged SCX4 rim and the positively charged ammonium group of the drugs, alongside C─H─π interactions.
• The resulting supramolecular assemblies exhibit significant thermoresponsive behavior.

Conclusions:

• Sulfonatocalixarenes effectively form stable supramolecular assemblies with specific drug molecules in aqueous solution.
• The identified interaction mechanisms provide a basis for designing tailored host-guest systems.
• The thermoresponsive nature of these assemblies opens avenues for developing novel functional materials for various applications.