Dinuclear nickel complexes modeling the structure and function of the acetyl CoA synthase active site

摘要

A dinuclear nickel complex with methyl and thiolate ligands, Ni(dadt~(Et))Ni(Me)(SDmp) (2), has been synthesized as a dinuclear Nid-Nip-site model of acetyl-CoA synthase (ACS) (dadt~(Et) is N.N'-diethyl-3,7-diazanonane-1,9-dithiolate; Dmp is 2,6-dimesitylphe-nyl). Complex 2 was prepared via 2 methods: (i) ligand substitution of a dinuclear Ni(II)-Ni(II) cation complex [Ni(dadt~(Et)) Ni(tmtu)_2] (OTf)_2 (1) with MeMgBr and KSDmp (tmtu is tetramethylthiourea), (ii) methyl transfer from methylcobaloxime Co(dmgBF_2)_2(Me)(Py) (5) to a Ni(ll)-Ni(0) complex such as [Ni(dadt~(Et))Ni(cod)] (3), generated in situ from Ni(dadt~(Et)) and Ni(cod)_2, followed by addition of KSDmp (cod is 1,5-cyclooctadiene; dmgBF_2 is difluoroboryl-dimethylglyoxi-mate). Method ii models the formation of Ni_p-Me species proposed as a plausible intermediate in ACS catalysis. The reaction of 2 with excess CO affords the acetylthioester CH_3C(O)SDmp (8) with concomitant formation of Ni(dadt~(Et))Ni(CO)_2 (9) and Ni(CO)_4 plus Ni(dadt~(Et)). When complex 2 is treated with 1 equiv of CO in the presence of excess 1,5-cyclooctadiene, the formation of 9 and Ni(CO)_4 is considerably suppressed, and instead the dinuclear Ni(II)-Ni(0) complex is generated in situ, which further affords 2 upon successive treatment with Co(dmgBF_2)2(Me)(Py) (5) and KSDmp. These results suggest that (i) ACS catalysis could include the Ni_d(M)-Ni_p(0) state as the active species, (ii) The Ni_d(II)-Ni_p(0) species could first react with methylcobalamin to afford Ni_d(II)-Ni_p(II)-Me, and (iii) CO insertion into the Ni_p-Me bond and the successive reductive elimination of acetyl-CoA occurs immediately when CoA is coordinated to the Ni_p site to form the active Ni_d(II)-Ni_p(0) species.