Antioxidant capacity of binuclear Cu(II)-cyclophanes, insights from two synthetic bioactive molecules

The compounds 2,9,25,32-tetraoxo-4,7,27,30-tetrakis(carboxymethyl)-1,4,7,10,24,27,30,33-octaaza-17,40-dioxa[10.1.10.1]paracyclophane and 2,9,25,32-tetraoxo-4,7,27,30-tetrakis(carboxymethyl)-1,4,7,10,24,27,30,33-octaaza[10.1.10.1]paracyclophane binuclear copper complexes (Cu₂PO and Cu₂PC, respectively) were studied by determining their antioxidant capacity using the TROLOX equivalent antioxidant capacity (TEAC) assay, and their cytotoxicity on cultured cells, as well as the superoxide dismutase (SOD)-like activity. Cu₂PO had an antioxidant capacity (0.1 g eq TROLOX mol^-1) within the order of magnitude of ascorbic acid, and both, Cu₂PO and Cu₂PC were nontoxic to cultured peripheral mononuclear blood cells. The SOD-like activity was evaluated using the nitroblue tetrazolium assay, and both compounds presented an excellent activity: for Cu₂PO, the IC₅₀ was 52 nM and for Cu₂PC an IC₅₀ of 0.5 μM was obtained comparable to CuZn SOD IC₅₀ 17 nM (Fernandes et al., J Inorg Biochem 2007;101:849-858). These results suggest that synthetic binuclear macrocycles are good candidates to be used as synthetic bioactive molecules with applications in biomedicine.