Mechanistic Aspects of Thioester Formation by Binuclear Nickel(II)-thiolate as a Functional Model of the Ni p Site of Acetyl-CoA Synthase

To understand the structure function of the Nip site of acetyl-CoA synthase (ACS), four nickel(II)-thiolates [NiII(Lp-ClPh(BzS))₂] (1), [NiII(Lp-ClPh(BzS))₂NiII(dppe)](ClO₄/BPh₄)₂ (2/2'), [NiII(Lp-ClPh(BzS))₂NiI(dppe)](ClO₄) (2red1), and [NiII(Lp-ClPh(BzS))₂NiI(dppe)(CO)₂](ClO₄), (2red1-(CO)₂) are synthesized and characterized, where HLp-ClPh(BzS)/dppe is an N₂Sthiol/P₂ donor ligand. Model 2/2' has a square planar NiIIP₂(μ-S)₂ moiety and partially resembles the square planar [{(μ-Scys)₃X}NiII] module, i.e., the Nip site of ACS. Electrochemistry and DFT calculations reveal that 2 is stable in its 1e⁻ (2red1), 2e⁻ (2red2), and 3e⁻ (2red3) reduced forms, exhibiting no thiol-S detachment of the model site. 2red1 and 2red2 as models enable to examine their thioester formation ability, relevant to the CoA-Ac synthesis by 1e⁻ and 2e⁻ reduced A-clusters, as proposed in paramagnetic and diamagnetic mechanisms of ACS catalysis, respectively, which are debatable. Reactions of 2red1 separately with CO, CH₃I, (CH₃I + CO), and (CH₃I + CO + Ph₃CSNa) are examined, and various intermediates/products formed are characterized by means of spectroelectrochemistry and various spectroscopy that reveal acetyl synthesis and deconstruction at the NiP₂S₂ site, as well as thioester (Ph₃C-SC(O)CH₃) formation along with 2red2. 2red2 binds CO to form 2red2-(CO)₂ but is unable to produce thioester. Combined experimental and theoretical results that give clue to the ability/inability of thioester formation by 2red1/2red2 are described in this paper.