A novel square-planar Ni(II) complex with an amino-carboxamido-dithiolato-type ligand as an active-site model of NiSOD.

Abstract

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, [Ni(2+)(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 (Epa) 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 Epa 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((16)O-(16)O)/ν((18)O-(18)O) = 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 (pKa 4.65) added as mimic of superoxide (pKa 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.