Homo- and Heterobinuclear Cu2+ and Zn2+ Complexes of Ditopic Aza Scorpiand Ligands as Superoxide Dismutase Mimics

• Published in: Inorganic chemistry 2017-11, Vol.56 (22), p.13748-13758
• Main Authors: Guijarro, Lluís, Inclán, Mario, Pitarch-Jarque, Javier, Doménech-Carbó, Antonio, Chicote, Javier U, Trefler, Sandra, García-España, Enrique, García-España, Antonio, Verdejo, Begoña
• Format: Article
• Language: English
• ISSN: 0020-1669; 1520-510X
• DOI: 10.1021/acs.inorgchem.7b01756

Two polytopic aza-scorpiand-like ligands, 6-[7-(diaminoethyl)-3,7-diazaheptyl]-3,6,9-triaza-1-(2,6-pyridina)­cyclodecaphane (L1) and 6-[6′-[3,6,9-triaza-1-(2,6-pyridina)­cyclodecaphan-6-yl]-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 voltammetry, and UV–vis spectroscopy. The resolution of the crystal structures of [Cu2 L2Cl2]­(ClO4)2·1.67H2O (1), [Cu2HL2Br2]­(ClO4)3·1.5H2O (2), and [CuZnL2Cl2]­(ClO4)2·1.64H2O (3) shows, in agreement with the solution data, the formation of homobinuclear Cu2+/Cu2+ and heterobinuclear Cu2+/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 L1 and L2 have been evaluated using nitro blue tetrazolium assays at pH 7.4. The IC50 and k cat values obtained for the [Cu2 L1]4+ complex rank among the best values reported in the literature for Cu-SOD mimics. Interestingly, the binuclear Cu2+ complexes of L1 and L2 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 Cu2+ ions in the different complexes.