Disulfide-Cross-Linked Tetra-PEG Gels

• Published in: Macromolecules 2024-04, Vol.57 (7), p.3058-3065
• Main Authors: Meng, Zhao, Löser, Lucas, Saalwächter, Kay, Gasser, Urs, Klok, Harm-Anton
• Format: Article
• Language: English
• Subjects: crosslinking; disulfides; hydrogels; neutrons; polymers; spectroscopy
• ISSN: 0024-9297; 1520-5835; 1520-5835
• DOI: 10.1021/acs.macromol.3c02514

The preparation of polymer gels via cross-linking of four-arm star-shaped poly­(ethylene glycol) (Tetra-PEG) precursors is an attractive strategy to prepare networks with relatively well-defined topologies. Typically, Tetra-PEG gels are obtained by cross-linking heterocomplementary reactive Tetra-PEG precursors. This study, in contrast, explores the cross-linking of self-reactive, thiol-end functional Tetra-PEG macromers to form disulfide-cross-linked gels. The structure of the disulfide-cross-linked Tetra-PEG gels was studied with multiple-quantum NMR (MQ-NMR) spectroscopy and small-angle neutron scattering (SANS) experiments. In line with earlier simulation studies, these experiments showed a strong dependence of the relative fractions of the different network connectivities on the concentration of the thiol-end functional Tetra-PEG macromer that was used for the synthesis of the networks. Disulfide-cross-linked Tetra-PEG gels prepared at macromer concentrations below the overlap concentration (c = 0.66c*) primarily feature defect connectivity motifs, such as primary loops and dangling ends. For networks prepared at macromer concentrations above the overlap concentration, the fraction of single-link connectivities was found to be similar to that in amide-cross-linked Tetra-PEG gels obtained by heterocomplementary cross-linking of N-hydroxysuccinimide ester and amine functional Tetra-PEG macromers. Since disulfide bonds are susceptible to reductive cleavage, these disulfide-cross-linked gels are of interest, e.g., as reduction-sensitive hydrogels for a variety of biomedical applications.