N 2 S 2 Ni Metallodithiolate Complexes as Ligands: Structural and Aqueous Solution Quantitative Studies of the Ability of Metal Ions to Form M-S-Ni Bridges to Mercapto Groups Coordinated to Nickel(II). Implications for Acetyl Coenzyme A Synthase Melissa L. Golden, † Curtis M. Whaley, ‡ Marilyn V. Rampersad, † Joseph H. Reibenspies, † Robert D. Hancock,* ,‡ and Marcetta Y. Darensbourg* ,† Departments of Chemistry, Texas A&M UniVersity, College Station, Texas 77843, and UniVersity of North Carolina at Wilmington, Wilmington, North Carolina 28403 Received July 30, 2004 The nickel(II) complex of an N 2 S 2 ligand, derived from a diazacycle, N,N′-bis(mercaptoethyl)-1,5-diazacycloheptane, (bme-dach)Ni, Ni-1′, serves as a metallodithiolate ligand to Ni II , Cu I , Zn II , Ag I , and Pb II . The binding ability of the NiN 2 S 2 ligand to the metal ions was established through spectrochemical titrations in aqueous media and compared to classical S-donor ligands. For M ) Ni, Zn, Pb, binding constants, log K ) ca. 2, were computed for 1:1 Ni-1′/M(solvate) adducts; for Ag + and Cu + , the 3:2 (Ni-1′) 3 M 2 adducts were the first formed products even in water with log  3,2 values of 26 and >30, respectively. In all cases, the binding ability of Ni-S-R is intermediate between that of a free thiolate and a free thioether. The great specificity for copper over nickel and zinc by N 2 S 2 Ni, which serves as a reasonable structural model for the distal nickel of the acetyl CoA synthase active site, relates to biochemical studies of heterogeneity (metal content and type) in various preparations of acetyl CoA synthase enzyme. The coordination chemistry of mercapto groups, derived from cysteine residues on proteins, is of major importance in biology. A dominant theme in complexes of ligands having mercapto groups is the formation of bridges between metal ions by mercapto sulfurs, as shown by the coordination chemistry of a widely investigated simple ligand such as mercaptoethanol (ME). Thus, of the 28 structures of com- plexes of this ligand reported in the Cambridge Structural Database, the majority involve sulfur donors bridging between two metal ions; also, where there is no bridging, steric hindrance prevents it, or the coordination number of the complexed metal ion is already satisfied by the coordi- nated ligands present. Formation constant studies in solution show that for virtually all of the complexes of ME with metal ions studied, polymeric species are present in solution. 1 As an example, for Zn(II) with ME the postulated solution species include [Zn 5 (ME) 12 ] 2- and [Zn 6 (ME) 15 ] 3- . 1 Depicted below are nickel(II) complexes of N 2 S 2 ligands derived from open chains such as N,N′-dimethyl-3,7-diaza- nonane-1,9-dithiolate (R ) Me) or N,N′-dimethyl-3,7-dia- zanonane-1,9-dithiolate (R ) Et), A; 2,3 N,N′-ethylenebis(2- mercaptoacetamide), B; 4 N,N′-bis(mercaptoethyl)-1,5-diaza- cyclooctane, the (bme-daco)Ni complex C; 5 and N,N′-bis- (mercaptoethyl)-1,5-diazacycloheptane, (bme-dach)Ni, D. 6 Such complexes present cis dithiolates whose S-based reactivity with a wide range of electrophiles is well estab- lished. The complexes (bme-daco)Ni and (bme-dach)Ni are prospects for study of binding to a variety of metal ions where the discrete N 2 S 2 Ni complexes can act as S-donor ligands. The square planar Ni(II) within the N 2 S 2 coordina- tion sphere is coordinatively saturated, and so has no tendency to form Ni-S-Ni sulfide bridges with itself. However, the coordinated mercapto groups on such com- * To whom correspondence should be addressed. E-mail: hancockr@uncw.edu (R.D.H.); marcetta@mail.chem.tamu.edu (M.Y.D.). † Texas A&M University. ‡ University of North Carolina at Wilmington. (1) Martell, A. E.; Smith, R. M. Critical Stability Constant Database, 46; National Institute of Science and Technology (NIST): Gaithers- burg, MD, 2003. (2) Lippard, S. J. Acc. Chem. Res. 1973, 6, 282-288. (3) Osterlohl, F.; Saak, W.; Pohl, S. J. Am. Chem. Soc. 1997, 119, 5648- 5656. (4) Kru ¨ger, H. J.; Peng, G.; Holm, R. H. Inorg. Chem. 1991, 30, 734- 742. (5) Mills, D. K.; Reibenspies, J. H.; Darensbourg, M. Y. Inorg. Chem. 1990, 29, 4364-4365. (6) Smee, J. J.; Miller, M. L.; Grapperhaus, C. A.; Reibenspies, J. H.; Darensbourg, M. Y. Inorg. Chem. 2001, 40, 3601-3605. Inorg. Chem. 2005, 44, 875-883 10.1021/ic0489701 CCC: $30.25 © 2005 American Chemical Society Inorganic Chemistry, Vol. 44, No. 4, 2005 875 Published on Web 01/05/2005