Two polytopic aza-scorpiand-like ligands, 647( diaminoethyl)-3,7-diazaheptyl] -3,6,9-triaza-1-( 2,6-pyridina) cyclo de cap bane (LI) and 6-[6'43,6,9-triaza-1-(2,6-pyridina)cyclo de cap han-6-y1]-3-azahexyl] -3,6,9-triaza-1-(2,6-pyridina)cyclodecaphane (L2), have been synthesized. The acid base behavior and Cu2+, Zn2+, and Cu2+/Zn2+ mixed coordination have been analyzed by potentiometry, cyclic voltamrnetry, and UV vis spectroscopy. The resolution of the crystal, structures of [Cu2L2Cl2] (ClO4)(2)center dot 1.67H(2)O (1), [Cu2HL2Br2] (ClO4)(3)center dot 1.5H(2)O (2), and [CuZnL2Cl2] (ClO4)(2)center dot 1.64H(2)O (3) shows, in agreement with the solution data, the formation of homobinuclear Cu2+/Cu2+ and heterobinuclear Ce2+/Zn2+ complexes. The metal ions are coordinated within the two macrocyclic cavities of the ligand with the involvement of a secondary amino group of the bridge in the case of 1 and 3. Energy dispersive X-ray spectroscopy confirms the 1:1 Cu2+/Zn2+ stoichiometry of 3. The superoxide dismutase (SOD) activities of the Cu2+/Cu2+ and Cu2+/Zn2+ complexes of Ll and L-2 have been evaluated using nitro blue tetrazolium assays at pH 7.4. The IC50 and kcat values obtained for the [Cu(2)L1](4+) complex rank among the best values reported in the literature for Cu-SOD mimics. Interestingly, the binuclear Cu2+ complexes of LI and L-2 have low toxicity in cultures of mammalian cell lines and show significant antioxidant activity in a copper -dependent SOD (SOD1)-defective yeast model. The results are rationalized by taking into account the binding modes of the Cu-2 ions in the different complexes.