Bisamidate and Mixed Amine/Amidate NiN2S2 Complexes as Models for Nickel-Containing Acetyl Coenzyme A Synthase and Superoxide Dismutase: An Experimental and Computational Study

摘要

The distal nickel site of acetyl-CoA synthase (Nid-ACS) and reduced nickel superoxide dismutase (Ni-SOD) display similar square-planar Ni^IIN2S2 coordination environments. One difference between these two sites, however, is that the nickel ion in Ni-SOD contains a mixed amine/amidate coordination motif while the Nid site in Ni-ACS contains a bisamidate coordination motif. To provide insight into the consequences of the different coordination environments on the properties of the Ni ions, we systematically examined two square-planar Ni^IIN2S2 complexes, one with bisthiolate-bisamidate ligation (Et4N)2(Ni(L1))·2H2O (>2) [H4L1 = N-(2-mercaptoacetyl)-N’-(2-mercaptoethyl)glycinamide] and another with bisthiolate-amine/amidate ligation K(Ni(HL2)) (>3) [H4L2 = N-(2“-mercaptoethyl)-2-((2’-mercaptoethyl)amino)acetamide]. Although these two complexes differ only by a single amine vs. amidate ligand, the chemical properties of them are quite different. The stronger in-plane ligand field in the bisamidate complex (Ni^II(L1))²⁻ (>2) results in an increase in the energies of the d → d transitions and a considerably more negative oxidation potential. Furthermore, while the bisamidate complex (Ni^II(L1))²⁻ (>2) readily forms a trinuclear species (Et4N)2({Ni(L1)}2Ni)·H2O (>1) and reacts rapidly with O2, presumably via sulfoxidation, the mixed amine/amidate complex (Ni^II(HL2))⁻ (>3) remains monomeric and is stable for days in air. Interestingly, the Ni^III species of the bisamidate complex formed by chemical oxidation with I₂ can be detected by electron paramagnetic resonance (EPR) spectroscopy while the mixed amine/amidate complex immediately decomposes upon oxidation. In order to explain these experimentally observed properties, we performed S K-edge X-ray absorption spectroscopy and low-temperature (77 K) electronic absorption measurements as well as both hybrid density functional theory (hybrid-DFT) and spectroscopy oriented configuration interaction (SORCI) calculations. These studies demonstrate that the highest occupied molecular orbital (HOMO) of the bisamidate complex (Ni^II(L1))²⁻ (>2) has more Ni character and is significantly destabilized relative to the mixed amine/amidate complex (Ni^II(HL2))⁻ (>3) by ~6.2 kcal mol⁻¹. The consequence of this destabilization is manifested in the nucleophilic activation of the doubly filled HOMO, which makes (Ni^II(L1))²⁻ (>2) significantly more reactive towards electrophiles such as O₂.