Supramolecular Hydrogels Based on Minimalist Amphiphilic Squaramide–Squaramates for Controlled Release of Zwitterionic Biomolecules

• Published in: Chemistry : a European journal 2017-06, Vol.23 (31), p.7590-7594
• Main Authors: López, Carlos, Ximenis, Marta, Orvay, Francisca, Rotger, Carmen, Costa, Antonio
• Format: Article
• Language: English
• Subjects: Acidity; Aromatic compounds; Aromaticity; Biomolecules; Carnitine; Catalysis; Chemistry; Controlled release; gels; Hydrogels; Mechanical properties; noncovalent interactions; Saline solutions; squaramides; Structural integrity; supramolecular chemistry; Thermodynamic properties; Zwitterions; γ-Aminobutyric acid
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201701029

Supramolecular hydrogels with tunable properties have innovative applications in biomedicine, catalysis, and materials chemistry. Minimalist low‐molecular‐weight hydrogelators based on squaramide and squaramic acid motifs have been designed. This approach benefits from the high acidity of squaramic acids and the aromaticity of squaramides. Moreover, substituents on the aryl ring tune the π density of the arylsquaramide motif. Thus, materials featuring distinct thermal and mechanical properties have been successfully prepared. The hydrogel (G′≈400 Pa, G′′≈57 Pa; at 1.0 % w/v; 1 Hz) obtained from 4‐nitrophenylsquaramide motif 1 is thermoreversible (T=57 °C at 0.2 % w/v), thixotropic, self‐healable, and undergoes irreversible shrinking in response to saline stress. Furthermore, the hydrogel is injectable and can be loaded with substantial amounts (5:1 excess molar ratio) of zwitterionic biomolecules, such as l‐carnitine, γ‐aminobutyric acid (GABA), or d,l‐Ala‐d,l‐Ala, without any loss of structural integrity. Then, the release of these molecules can be modulated by saline solutions. Drop the payload! Smart supramolecular hydrogels based on squaramides and squaramate synthons are thermoreversible, thixotropic, and injectable. These hydrogels can be loaded with zwitterions and display ion‐stimulated shrinking and release of the payload (see figure). This combination of properties is unusual in supramolecular hydrogels derived from low‐molecular‐weight hydrogelators.