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.