A Novel Square-Planar Ni(II) Complex with an AminoCarboxamidoDithiolato-Type Ligand as an Active-Site Model of NiSOD

To understand the role of the unique equatorial coordination environment at the active center in nickel superoxide dismutase (NiSOD), we prepared a novel Ni­(II) complex with an amino–carboxamido–dithiolato-type square-planar ligand (1, [Ni2+(L1)]−) as a model of the NiSOD active site. Complex 1 has a low-spin square-planar structure in all solvents. Interestingly, the absorption wavelength and ν­(CO) stretching vibrations of 1 are affected by solvents. This provides an indication that the carbonyl oxygens participate in hydrogen-bonding interactions with solvents. These interactions are reflected in the redox potentials; the peak potential of an anodic wave (E pa) values of Ni­(II)/Ni­(III) waves for 1 are shifted to a positive region for solvents with higher acceptor numbers. This indicates that the disproportionation of superoxide anion by NiSOD may be regulated by hydrogen-bonding interactions between the carboxamido carbonyl and electrophilic molecules through fine-tuning of the redox potential for optimal SOD activity. Interestingly, the E pa value of the Ni­(III)/Ni­(II) couple in 1 in water (+0.303 V vs normal hydrogen electrode (NHE)) is similar to that of NiSOD (+0.290 V vs NHE). We also investigated the superoxide-reducing and -oxidizing reactions of 1. First, 1 reacts with superoxide to yield the superoxide-bound Ni­(II) species (UV–vis: 425, 525, and ∼650 nm; electron paramagnetic resonance (EPR) (4 K): g // = 2.21, g ⊥ = 2.01; resonance Raman: ν­(16O–16O)/ν­(18O–18O) = 1020/986 cm–1), which is then oxidized to Ni­(III) state only in the presence of both a proton and 1-methylimidazole, as evidenced by EPR spectra. Second, EPR spectra indicate that the oxidized complex of 1 with 1-methylimidazole at the axial site can be reduced by reaction with superoxide. The Ni­(III) complex with 1-methylimidazole at the axial site does not participate in any direct interaction with azide anion (pK a 4.65) added as mimic of superoxide (pK a 4.88). According to these data, we propose the superoxide disproportionation mechanism in superoxide-reducing and -oxidizing steps of NiSOD in both Ni­(II) and Ni­(III) states.