Abstract: | The model complex Cu4(μ4‐S)(dppa)4]2+ ( 1 , dppa=μ2‐(Ph2P)2NH) has N2O reductase activity in methanol solvent, mediating 2 H+/2 e? reduction of N2O to N2+H2O in the presence of an exogenous electron donor (CoCp2). A stoichiometric product with two deprotonated dppa ligands was characterized, indicating a key role of second‐sphere N?H residues as proton donors during N2O reduction. The activity of 1 towards N2O was suppressed in solvents that are unable to provide hydrogen bonding to the second‐sphere N?H groups. Structural and computational data indicate that second‐sphere hydrogen bonding induces structural distortion of the Cu4S] active site, accessing a strained geometry with enhanced reactivity due to localization of electron density along a dicopper edge site. The behavior of 1 mimics aspects of the CuZ catalytic site of nitrous oxide reductase: activity in the 4CuI:1S redox state, use of a second‐sphere proton donor, and reactivity dependence on both primary and secondary sphere effects. |