Nickel superoxide dismutase (NiSOD) is a metalloenzyme that can catalyze the disproportionation of superoxide (O2) to O2 and H2O2 at the diffusion-controlled rates. In the NiSOD active site, the Ni ion is situated in a mixed amine/peptide thiolates N3S2 coordination environment. The unique NiSOD active site promotes facile Ni(III/II) redox while prevents the oxidation/oxygenation of thiolates by the substrate and products of O2 disproportionation. This has prompted the development of relatively small synthetic analogues of NiSOD by our group and others to understand the role of mixed N/S donors in NiSOD. We reported the first five-coordinate (5C) analogue, K[Ni(N3S2)] (1), that replicates the N3S2 donor set of NiSOD structurally and electronically with a pendant pyridine as potential fifth ligand to Ni in the axial position. However, oxidation of 1 by ferrocenium hexafluorophosphate (FcPF6) yielded a disulfide-bridged complex. The increased in basicity as well as steric enforcement by incorporation of gem-(CH3)2 moiety in the second-generation analogue, Na[Ni(N3S2Me2)] (2), is expected to promote Ni-based redox while preventing disulfide formation at the S trans to carboxamide. However, the increase in steric enforcement in 2 led to a new oxidation pathway that yielded a thiazolidine ring rearrangement product that was not observed in 1. Since coordination of axial N-ligand to Ni is critical in promoting Ni-based redox in NiSOD, the pendant pyridine is replaced with N-ethylmorpholine (NEM) moiety in the third-generation analogue, Na[Ni(N3S2NEM)] (3). The more Lewis basic N-donor in 3 is expected to coordinate to both Ni2+ and Ni3+ oxidation state to promote Ni-based redox. Reactions of 3 with oxidants (air, FcPF6, and KO2) and Lewis acid (i.e. tris(pentafluorophenyl) borane) yielded stair-step trimetallic species with N-NEM poised to coordinate to terminal [NiN3S2] centers. CV of these trimetallic species exhibited multiple reversible redox couples assigned to the terminal [NiN3S2] centers. These results show that while 1-3 can replicate NiSOD active site electronically and structurally, reversible Ni(III/II) redox couple is not achievable unless the electron density on S-thiolates is sequestered by Lewis acids (i.e., Ni2+ and borane), which mimics the H-bond interactions in NiSOD active site.