Ligand Radicals Tune LPMO Activity in Model Complex

Radicals are essential to the catalytic chemistry of metalloenzymes, enabling reactivity and self-protection through controlled redox processes. In copper-dependent LPMOs, amino acid radicals mediate oxidative transformations via hole hopping. However, the generation and role of ligand-centered radicals in synthetic copper models remain poorly understood. Here we show that an l-proline-based N,N,O,O-coordinated copper complex (4) generates stable carbon-centered ligand-radicals. A markedly higher population of these ligand radicals was observed in this complex than in the N,N,N-coordinated analogues (complexes 1-3). Catalytically, complex 4 outperforms complexes 1-3, effectively degrading 4-nitrophenyl-β-d-glucopyranoside, cellobiose, and cellulose using either H₂O₂ or O₂. The superior performance of complex 4 is linked to its lower steric hindrance, a key factor in LPMO mimicry. These results establish ligand-centered radicals as key functional analogues of enzymatic redox pathways and offer a blueprint for designing self-protecting copper oxidation catalysts.