Steric Enforcement about One Thiolate Donor Leads to New Oxidation Chemistry in a NiSOD Model Complex

Ni-containing superoxide dismutase (NiSOD) represents an unusual member of the SOD family due to the presence of oxygen-sensitive Ni-SCys bonds at its active site. Reported in this account is the synthesis and properties of the Ni^II complex of the N₃S₂ ligand [N₃S₂^Me2]^3- ([N₃S₂^Me2]^3- = deprotonated form of 2-((2-mercapto-2-methylpropyl)(pyridin-2-ylmethyl)amino)-N-(2-mercaptoethyl)acetamide), namely Na[Ni(N₃S₂^Me2)] (2), as a NiSOD model that features sterically robust gem-(CH₃)₂ groups on the thiolate α-C positioned trans to the carboxamide. The crystal structure of 2, coupled with spectroscopic measurements from ¹H NMR, X-ray absorption, IR, UV-vis, and mass spectrometry (MS), reveal a planar Ni^II (S = 0) ion coordinated by only the N₂S₂ basal donors of the N₃S₂ ligand. While the structure and spectroscopic properties of 2 resemble those of NiSOD_red and other models, the asymmetric S ligands open up new reaction paths upon chemical oxidation. One unusual oxidation product is the planar Ni^II-N₃S complex [Ni(L^ox)] (5; L^ox = 2-(5,5-dimethyl-2-(pyridin-2-yl)thiazolidin-3-yl)-N-(2-mercaptoethyl)acetamide), where two-electron oxidation takes place at the substituted thiolate and py-CH₂ carbon to generate a thiazolidine heterocycle. Electrochemical measurements of 2 reveal irreversible events wholly consistent with thiolate redox, which were identified by comparison to the Zn^II complex Na[Zn(N₃S₂^Me2)] (3). Although no reaction is observed between 2 and azide, reaction of 2 with superoxide produces multiple products on the basis of UV-vis and MS data, one of which is 5. Density functional theory (DFT) computations suggest that the HOMO in 2 is π* with primary contributions from Ni-dπ/S-pπ orbitals. These contributions can be modulated and biased toward Ni when electron-withdrawing groups are placed on the thiolate α-C. Analysis of the oxidized five-coordinate species 2^ox* by DFT reveal a singly occupied spin-up (α) MO that is largely thiolate based, which supports the proposed Ni^III-thiolate/Ni^II-thiyl radical intermediates that ultimately yield 5 and other products.