Ligand Exchange on Zr/Hf-Oxo Clusters: Mechanistic Insights and Implications for Catalysis.

Atomically precise group IV metal-oxo clusters, consisting of structured Zr/Hf oxo nodes capped by labile ligands, are emerging as versatile catalysts at the interface of homogeneous and heterogeneous chemistry. Their catalytic activity arises from the inherent Lewis acidity and oxophilicity associated with the metal centers, which enable coordination to electron-donating functional groups such as carboxylates, phosphates, and amides. As a result, metal-oxo clusters can catalyze a broad range of bond activation and transformation reactions, including (trans)esterification and hydrolysis. Discrete metal-oxo clusters undergo rapid surface ligand exchange that governs substrate binding, activation, and product release. By tuning the identity, number, and lability of these ligands, the accessibility of Lewis acidic sites can be controlled, thereby modulating reactivity toward amide bond hydrolysis in peptides and proteins, a benchmark reaction that sensitively probes how ligands regulate substrate access and binding. In addition, Zr/Hf-oxo clusters display tunable solubility, enabling catalysis under both homogeneous and heterogeneous conditions. Using representative soluble and insoluble Zr/Hf-oxo clusters, we show that ligand dynamics critically modulate reactivity both in solution and at solid-liquid interfaces. Specifically, we present an overview of mechanistic insights focusing on: (i) the soluble Zr6 cluster, where ligand exchange drives reactivity, (ii) the insoluble Zr17 and Hf18 clusters, where the ligand shell modulates the reactivity by influencing adsorption-desorption dynamics, and (iii) a comparative study of soluble and insoluble Hf12 clusters, highlighting how ligand shell occupation controls reactivity across phases. Together, these studies establish ligand exchange at cluster surfaces as a key design parameter to tune catalytic activity and provide a basis for the development of next-generation cluster catalysts with enhanced stability, selectivity, and recyclability.