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.