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.