Nickel superoxide dismutase (Ni-SOD) is a recently discovered SOD obtained from soil microbes and cyanobacteria that shares no structural or spectroscopic similarities with other isoforms of SOD. The enzyme is found in both the Ni-II (Ni-SODred) and (Ni-SOD,) oxidation states in "as isolated" preparations of the enzyme from two separate and independently crystallized Streptomyces strains. Ni-SOD contains an unusual and unprecedented biological coordination sphere comprised of Cys-S and peptido-N donors. To understand the role of these donors, we have previously synthesized the monomeric (NiN2S2)-N-II complexes, (Et4N)[Ni(nmp)(SC6H4-p-Cl)] (2) and (Et4N)[Ni(nmp)-((SBu)-Bu-t)] (3) as Ni-SODred models arising from the S,S-bridged precursor molecule, [Ni-2(nmp)(2)] (1) (where nmp(2-) = doubly deprotonated form of N-2-(mercaptoethyl)picolinamide). In addition to 2 and 3, we report here three new complexes, (Et4N)[Ni(nmp)(S-o-babt)] (4), (Et4N)[Ni(nmp)(S-meb)] (5), and K[Ni(nmp)(S-NAc)] (6) (where S--o-babt = thiolate of o-benzoylaminobenzene thiol; S-meb = thiolate of N-(2-mercaptoethyl)benzamide; and S-NAc = thiolate of N-acetyl-L-cysteine methyl ester), that provide a unique comparison as to the structural and reactivity effects imparted by H-bonding in square planar asymmetrically coordinated (NiN2S2)-N-II complexes. X-ray structural analysis in combination with cyclic wvoltammetry (CV), spectroscopic measurements, density functional theory (DFT) calculations, and reactivity studies with O-2 and various ROS were employed to gain insight into the role that H-bonding plays in NiN2S2 complexes related to Ni-SOD. The experimental results coupled with theoretical analysis demonstrate that H-bonding to coordinated thiolates stabilizes S-based molecular orbitals relative to those arising from Ni-II, allowing for enhanced Ni contribution to the highest occupied molecular orbital (HOMO), which is predominantly of S Ni character. These studies provide a unique perspective on the role played by electronically different thiolates regarding the intimately coupled interplay and delicate balance of Ni- versus S-based reactivity in Ni-SOD model complexes. The reported results have offered new insight into the chemistry that H-bonding/thiolate protonation imparts upon the Ni-SOD active site during catalysis, in particular, as a protective mechanism against oxidative modification/degradation.