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) 3XNiII 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.