The supramolecular biomimetic chemistry based on calix[6]arene N-ligands has been further explored. A tris(imidazole)CuI complex was treated with 1 mol-equiv. of cuprous ion under dioxygen to produce a tetranuclear cupric species, X-ray structural determination of this novel Cu4 complex revealed that the self-inclusion of an imidazolyl coordinating arm into the hydrophobic calixarene cavity provides the base of coordination for a _ClImCu(OH)2CuIm2₂ assembly. The Cu4 core is maintained in solution and is stable even in a coordinating solvent such as acetonitrile. Magnetic susceptibility measurements evidenced a strong antiferromagnetic coupling in each Cu(OH)2Cu subunit with J = -408 cm-1. The complex displayed catecholase activity in the presence of 3,5-di-tert-butylcatechol behaving as a four-electron hole with, however, a sluggish Cu4 I → Cu4 II regeneration through O2 autooxidation. Finally, electrochemical studies revealed two oxidative reversible processes that successively gave rise to a _CuIICuIII__Cu2 II_ and a _CuIICuIII₂ mixed-valence species that could be characterized by UV/Vis and EPR spectroscopy, The overall structure and behavior of this tetranuclear complex is reminiscent of multicopper enzymes. © Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.