Insights into the Controlled Formation of Zr-Based Metal-Organic Gels: Linking Macroscopic Properties with Molecular Information from Solution State NMR.

Understanding and controlling the formation mechanisms of metal-organic gels is crucial for their rational design with well-defined properties for diverse applications. However, rapid methodologies enabling atomic-resolution structural characterization of gel formation are still largely lacking. Here, we report for the first time the molecular-level characterization of the in-situ formation of a Zr-based metal-organic gel by monitoring solvent structuration during gelation using solvent-observed nuclear magnetic resonance (NMR) spectroscopy. UiO-66-type gels were optimized under mild conditions, i.e., 40 °C and in the absence of acidic modulators, providing a biocompatible environment suitable for the in-situ encapsulation of sensitive biomolecules during gelation. The combined analysis of saturation transfer difference and spin diffusion transfer difference NMR growth curves enabled real time monitoring of nucleation and gelation stages, revealing an excellent correlation between the progressive structuration of water within the gel network and the resulting macroscopic properties. Furthermore, we demonstrate that this NMR approach allows tracking of the in-situ encapsulation of therapeutic biomolecules within the gel, exemplified by a glycolipid with anti-inflammatory properties.