Insights into the Gelation Mechanism of Metal-Coordinated Hydrogels by Paramagnetic NMR Spectroscopy and Molecular Dynamics

Metal-coordination complexes are attracting increasing attention as supramolecular cross-linkers to develop polymeric hydrogel networks with tunable and dynamic mechanical properties. Nonetheless, the rational design of these materials is still hindered by the limited mechanistic understanding of how metal–ligand interactions influence the structure and properties of the hydrogel. Here, we report a detailed mechanistic investigation using nuclear magnetic resonance (NMR) spectroscopy combined with molecular dynamics (MD) simulations to explore the formation of cellulose-based hydrogels induced by coordination with paramagnetic Fe3+ ions. We demonstrate how NMR paramagnetic relaxation enhancement can be used to probe the distances between the metal center and NMR active nuclei on the polymer chain, informing on the metal–ligand coordination network. Experimental results, together with supporting MD simulations, allow us to uncover a structuration of water around the cross-linked metals within the hydrogel, in addition to the establishment of different orientations of the chains governed by hydrogen bonds networks. Progress in understanding the gelation mechanism of metal-coordinated hydrogels will fuel their exploitation for a wide variety of biomedical applications.