Remote allosteric control of single-atom Cu sites in Zr-MOFs enables selective CH4 hydroxylation.

Highly selective oxidation of methane to liquid oxygenates under mild conditions remains challenging because of the difficulty in controlling overoxidation at highly reactive sites. Here, we demonstrate remote control of single-atom Cu reactivity through outer-shell coordination engineering in Zr-based metal-organic frameworks (MOFs). By anchoring Cu1 to Zr-oxo nodes in UiO-66-X (X = -NO2, -H, and -CH3), remote X-BDC ligands systematically modulate the electronic properties of Cu1 sites and the catalytic microenvironment. In situ characterization combined with ab initio molecular dynamics in an explicitly solvated aqueous environment reveals a dynamic outer-shell-to-inner-shell regulation that reshapes the active structure and reactive oxygen species around Cu1 sites, thereby facilitating CH4 activation. In particular, the electron-withdrawing NO2-BDC ligand creates electron-deficient Cu1-•OH* sites, while adsorbed water further regulates active-site conformation. Consequently, Cu1/U6-NO2 achieves a turnover frequency of 322.4 h-1 with nearly 100% oxygenate selectivity under mild conditions, establishing a general strategy for overcoming activity-selectivity trade-offs in methane conversion.