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 Ni_p site of acetyl-CoA synthase (ACS), four nickel(II)-thiolates [Ni^II(L^p-ClPh(BzS))₂] (<b>1</b>), [Ni^II(L^p-ClPh(BzS))₂Ni^II(dppe)](ClO₄/BPh₄)₂ (<b>2/2'</b>), [Ni^II(L^p-ClPh(BzS))₂Ni^I(dppe)](ClO₄) (<b>2</b>^<b>red1</b>), and [Ni^II(L^p-ClPh(BzS))₂Ni^I(dppe)(CO)₂](ClO₄), (<b>2</b>^<b>red1</b>-(CO)₂) are synthesized and characterized, where HL^p-ClPh(BzS)/dppe is an N₂S^thiol/P₂ donor ligand. Model <b>2/2'</b> has a square planar Ni^IIP₂(μ-S)₂ moiety and partially resembles the square planar [{(μ-S^cys)₃X}Ni^II] module, i.e., the Ni_p site of ACS. Electrochemistry and DFT calculations reveal that <b>2</b> is stable in its 1e^- (<b>2</b>^<b>red1</b>), 2e^- (<b>2</b>^<b>red2</b>), and 3e^- (<b>2</b>^<b>red3</b>) reduced forms, exhibiting no thiol-S detachment of the model site. <b>2</b>^<b>red1</b> and <b>2</b>^<b>red2</b> 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 <b>2</b>^<b>red1</b> 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 <b>2</b>^<b>red2</b>. <b>2</b>^<b>red2</b> binds CO to form <b>2</b>^<b>red2</b>-(CO)₂ but is unable to produce thioester. Combined experimental and theoretical results that give clue to the ability/inability of thioester formation by <b>2</b>^<b>red1</b>/<b>2</b>^<b>red2</b> are described in this paper.