Comparison of Protective Effects against Reactive Oxygen Species of Mononuclear and Dinuclear Cu(II) Complexes with N-Substituted Benzothiazolesulfonamides

Copper(II) complexes of N-benzothiazolesulfonamides (HL1 = N-2-(4-methylphenylsulfamoyl)-6-nitro-benzothiazole, HL2 = N-2-(phenylsulfamoyl)-6-chloro-benzothiazole, and HL3= N-2-(4-methylphenylsulfamoyl)-6-chloro-benzothiazole) with ammonia have been synthesized and characterized. The crystal structures of the [Cu(L1)2(NH3)2]·2MeOH (1), [Cu(L2)2(NH3)2] (2), and [Cu(L3)2(NH3)2] (3) compounds have been determined. Compounds 1 and 2 present a distorted square planar geometry. In both compounds the metal ion is coordinated by two benzothiazole N atoms from two sulfonamidate anions and two NH3 molecules. Complex 3 is distorted square-pyramidal. The Cu(II) ion is linked to the benzothiazole N and sulfonamidate O atoms of one of the ligands, the benzothiazole N of another sulfonamidate anion, and two ammonia N atoms. We have tested the superoxide dismutase (SOD)-like activity of the compounds and compared it with that of two dinuclear compounds [Cu2(L4)2(OCH3)2(NH3)2] (4) and [Cu2(L4)2(OCH3)2(dmso)2] (5) (HL4 = N-2-(phenylsulfamoyl)-4-methyl-benzothiazole). In vitro indirect assays show that the dimeric complexes are better SOD mimics than the monomeric ones. We have also assayed the protective action provided by the compounds against reactive oxygen species over Δsod1 mutant of Saccharomyces cerevisiae. In contrast to the in vitro results, the mononuclear compounds were more protective to SOD-deficient S. cerevisiae strains than the dinuclear complexes.