Electrophilic Modulation of the Superoxide Anion Radical Scavenging Ability of Copper(II) Complexes with 4-Methyl...

Three Cu(II) coordination compounds with 4-methyl imidazole were obtained, such as [Cu(C₄H₆N₂)₄(NO₃)₂], [Cu(C₄H₆N₂)₄Br₂], and [Cu(C₄H₆N₂)₄Cl₂]. Crystallographic studies confirmed their structural similarity with Cu(II) in the active site of endogenous copper-zinc superoxide dismutase (CuZn-SOD). The superoxide anion radical (O₂^•-) scavenging activity was evaluated by the non-enzymatic experimental assay and followed the trend [Cu(C₄H₆N₂)₄(NO₃)₂] > [Cu(C₄H₆N₂)₄Br₂] > [Cu(C₄H₆N₂)₄Cl₂]. The density functional theory and the hard and soft acids and bases principle showed the importance of the electron-deficient character of Cu(II) in the chemical reactivity of the coordination compounds; Cu(II) is the softest site in the molecule and it is preferred for the nucleophilic and radical attacks of the soft O₂^•-. A simple rule was obtained: "the electron-deficient character of Cu(II) is the key index for the O₂^•- scavenging activity and is modulated by the electron-releasing counteranion effect on the coordination compound".