Unraveling Water Sorption in Single‐Crystal MOFs: Insights from Spectroscopy and Modeling on the Role of Structure, Composition, and Guest Molecules

ABSTRACT Understanding water sorption in metal‐organic frameworks (MOFs) is essential for advancing atmospheric water harvesting (AWH). Yet, most studies rely on bulk measurements that mask intrinsic material properties and particle heterogeneity. Here, we systematically examine how defect chemistry, residual guest molecules, and metal substitution shape water uptake in MOF‐801 and MOF‐808 at the single‐crystal level. Using bulk characterization together with in situ single‐crystal Raman spectroscopy, digestion ¹ H NMR, computational modeling, and long‐term cycling experiments, we disentangled how substituting Zr with Hf and changing topology affect the sorption behavior. Single‐crystal measurements reveal substantial crystal‐to‐crystal variations in residual DMF, which directly reduce the accessible pore volume and alter adsorption isotherms—effects hidden in ensemble‐averaged data. In both MOFs, Zr‐based materials exhibit higher uptake due to defect‐induced porosity. Hf substitution lowers the intrinsic defect density and improves cycling stability, but also leads to stronger solvent coordination and reduced pore accessibility. This trade‐off is most pronounced in MOF‐808(Zr), which shows high uptake but collapses during cycling, whereas the Hf analogue remains structurally stable at reduced capacity. By resolving how defects, guest molecules, and metal identity interplay at the single‐crystal level, this work provides molecular design rules for balancing stability and performance in next‐generation AWH sorbents.