Supramolecular gel formation regulated by water content in organic solvents: self-assembly mechanism and biomedical applications

Abstract

As one of the most important and fruitful methods, supramolecular self-assembly has a significant advantage in designing and fabricating functional soft materials with various nanostructures. In this research, a low-molecular-weight gelator, N,N′-di(pyridin-4-yl)-pyridine-3,5-dicarboxamide (PDA-N4), was synthesized and used to construct self-assembled gels via a solvent-mediated strategy. It was found that PDA-N4 could form supramolecular gels in mixed solvents of water and DMSO (or DMF) at high water fraction (greater than or equal to 50%). By decreasing the water fraction from 50% to 30%, the gel, suspension and solution phases appeared successively, indicating that self-assembled aggregates could be efficiently modulated via water content in organic solvents. Moreover, the as-prepared PDA-N4 supramolecular gels not only displayed solid-like behavior, and pH- and thermo-reversible characteristics, but also showed a solution–gel–crystal transition with the extension of aging time. Further analyses suggested that both the crystal and gel had similar assembled structures. The intermolecular hydrogen bonding between amide groups and the π–π stacking interactions between pyridine groups played key roles in gel formation. Additionally, the release behavior of vitamin B12 (VB₁₂) from PDA-N4 gel (H₂O/DMSO, v/v = 90/10) was evaluated, and the drug controlled release process was consistent with a first-order release mechanism. The human umbilical venous endothelial cell culture results showed that the PDA-N4 xerogel has good cytocompatibility, which implied that the gels have potential biological application in tissue engineering and controlled drug release.