Domino Effect in Epimer Self-Assembly Induces Diverse Hydrogel Properties for Biomedical Applications

Area of Science:

• Supramolecular Chemistry
• Materials Science
• Biomaterials Engineering

Background:

• Precise control over small-molecule self-assembly is crucial for designing advanced supramolecular architectures.
• Subtle molecular structural changes can lead to significant alterations in self-assembly behavior and material properties.

Purpose of the Study:

• To investigate the impact of C18-epimerization of glycyrrhizic acid (GA) on its self-assembly and hydrogel properties.
• To establish a stereochemical strategy for engineering functional supramolecular biomaterials.

Main Methods:

• Computational simulations to analyze molecular interactions and self-assembly pathways.
• Experimental characterization of hydrogel networks, including hydrogen bonding and structural analysis.
• Evaluation of hydrogel properties such as injectability, viscosity, and drug delivery capabilities.

Main Results:

• C18-epimerization of GA to isoglycyrrhizic acid (IGA) fundamentally alters self-assembly via a domino effect, reshaping the hydrogen-bonding network.
• IGA forms a densely crosslinked fiber network with enhanced hydrogen bonding due to altered electrostatic potential and planarity.
• IGA-based hydrogels exhibit improved injectability and viscosity, and enhance therapeutic agent dispersibility and efficacy in preclinical models.

Conclusions:

• Molecular epimerization serves as a switch to control self-assembly and hydrogel properties.
• IGA-based hydrogels offer a promising platform for advanced biomaterials and drug delivery systems.
• Stereochemistry plays a pivotal role in dictating the macroscopic functions of supramolecular biomaterials.