Unravelling Ice Growth Inhibition by UiO-66 and Its Functionalized Nanoparticles: The Role of Uncoordinated Linkers...

In organ transplantation, cryogenic storage of live cells is essential, but ice recrystallization during thawing causes cell damage, necessitating effective control strategies. Ice recrystallization inhibition (IRI) agents suppress ice growth through the Gibbs-Thomson effect by binding to the ice surface. Metal-organic framework (MOF) nanoparticles, with high surface area and tunable chemistry, show strong promise as effective IRI agents; however, their inhibition mechanisms and the role of surface modifications remain insufficiently understood. In this work, we performed the first computational investigation of using UiO-66 and its functionalized derivative MOF nanoparticles with surface-modified uncoordinated linkers as IRI agents through MD simulations. We observed that the MOF nanoparticles were highly effective in inhibiting ice growth through the Gibbs-Thomson effect, with the UiO-66 nanoparticle reducing the growth rate by up to 24% compared to the benchmark ice-water system. Further, we observed that the UiO-66 nanoparticle produced the highest thermal hysteresis close to 12 K. Additionally, we showed that the adsorbed surface area of the nanoparticle plays a major role in inhibiting ice growth compared to the number of hydrogen bonds formed, deviating from previous conclusions in the literature. Through PMF calculations, we also observed that the presence of uncoordinated linkers on the MOF nanoparticle improved the binding strength of the nanoparticle to the ice surface, with UiO-66 showing a potential of mean force (PMF) of 2.9 kcal mol^-1 per linker. To the best of our knowledge, this work represents the first computational investigation of ice recrystallization inhibition in MOF nanoparticles with uncoordinated linker modifications, and it establishes surface functionalization as an effective strategy for enhancing their IRI activity.