Metalloprotein Models

Discerning the structural and functional characteristics that are essential to the role of metal ions in metalloenzymes is a focus of our group. Our approach to this problem is to construct small-molecule analogs of the metal ion active site. These analogs, or model complexes, allow for atomic-level control over the metal ion geometry and ligand environment in a way that is often not possible when working directly with large biological systems. Through organic and inorganic synthesis, we are able to construct covalently linked, polydentate ligands and their corresponding metal complexes that mimic key structural aspects of a protein's active site. We then use various chemical tools to study their reactivity and mechanism.

In general, the chemistry of nonheme iron centers is of broad significance in biology and in synthetic chemistry. In particular, the reactivity of non-heme iron with oxygen-derived adducts has special prominence. Recent efforts have focused on constructing synthetic models of metalloenzymes that contain mixed nitrogen/sulfur donors in their active sites. One example of such a metalloenzyme is the non-heme iron enzyme superoxide reductase (SOR). This enzyme catalyzes only the reduction of O2- to H2O2, not its disproportionation, as seen with the more common SODs. The active site contains an unusual 4His/1Cys ligand environment for an Fe(II)/Fe(III) center. The mechanism of SOR and proposed intermediates, such as a (hydro)peroxo-iron(III) species, are not well understood. We have synthesized a new family of {N4S(thiolate)}-ligated iron(II) complexes as models of SOR, and have trapped various alkylperoxo-iron(III) intermediates at low temperature with these systems.

Selected Publications

X-ray Absorption Spectroscopy and Reactivity of Thiolate-Ligated Fe(III)-OOR Complexes
Stasser, J.; Namuswe, F.; Kapser, G.D.; Jiant, Y.; Krest, C.; Green, M.T.; Penner-Hahn, J.; Goldberg*, D.P.; Inorg. Chem., 2010, ASAP.

Iron(II)-Thiolate S-Oxygenation By O2: Synthetic Models of Cysteine Dioxygenase
Jiang, Y.; Widger, L. R.; Kasper, G. D.; Siegler, M. A.; Goldberg*, D. P.; J. Am. Chem. Soc. 2010, 132, 12214- 12215.

Evidence for the Formation of a Mononuclear Ferric-Hydroperoxo Complex via the Reaction of Dioxygen with an (N4S(thiolate))iron(II) Complex
Jiang, Y.; Telser, J.; Goldberg*, D. P.; Chem. Commun. 2009, 44, 6828- 6830.

Influence of the Nitrogen Donors on Non-Heme Iron Models of Superoxide Reductase: High-Spin Fe(III)-OOR Donors on Non-Heme Iron Models of Superoxide Reductase
Namuswe, F.; Hayashi, T.; Jiang, Y.; Kasper, G. D.; Sarjeant, A. A. N.; Moënne-Loccoz, P.; Goldberg*, D.P.; J. Am. Chem. Soc. 2010, 132, 157- 167.

Rational Tuning of the Thiolate DOnor in Model Complexes of Superoxide Reductase: Direct Evidence for a trans influence in Fe(III)-OOR Complexes
Namuswe, F.; Kapser, G.D.; Sarjeant, A. A. N.; Krest, C.; Hayashi, T.; Green, M.T.; Moenne-Loccoz, P.; Goldberg*, D.P.; J. Am. Chem. Soc. 2008, 130, 14189- 14200.

Characterization of the First N2S(alkylthiolate)lead Compound: A model for Three-Coordinate Lead in Biological Systems
Anderson, R. J.; Di Targiani, R. C.; Hancock, R. D.; Stern, C. L.; Goldberg, D. P.; Godwin, H. A.; Heterocycles 2008, 76, 1369-1380.

A Low-Spin Alkylperoxo-Iron(III) Complex with weak Fe-O and O-O Bonds: Implications for the Mechanism of Superoxide Reductase
Krishnamurthy, D.; Kasper, G.D.; Namuswe, F.; Kerber, W.D.; Sarjeant, A.; Moenne-Loccoz, P.; Goldberg*, D.P.; J. Am. Chem. Soc. 2006, 128, 14222- 14223.

A Combinatorial Approach to Minimal Peptide Models of a Metalloprotein Active Site
Namuswe, F.; Goldberg*, D.P.; Chem. Comm. 2006, 2326-2328.

Geometric Preferences in Iron(II) and Zinc(II) Model Complexes of Peptide Deformylase
Karambelkar, V.V.; Xiao, C.; Zhang, Y.; Sarjeant, A.A.N.; Goldberg*, D.P.; Inorg. Chem. 2006, 45, 1409-1411.

Phosphate Triester Hydrolysis Promoted by an N2S(thiolate)Zinc Complex: Mechanistic Implications for the Metal-Dependent Reactivity of Peptide Deformylase
Goldberg*, D.P.; diTargiani, R.C.; Namuswe, F.; Minnihan, E.C.; Chang, S.; Zakharov, L.N.; Rheingold, A.L.; Inorg. Chem. 2005, 44, 7559-7569.

Mononuclear, Dinuclear, and Pentanuclear (N,S(thiolate))Iron(II) Complexes: Nuclearity Control, Incorporation of Hydroxide Bridging Ligands, and Magnetic Behavior
Krishnamurthy, D.; Sarjeant, A.; Goldberg*, D.P.; Caneschi, A.; Totti, F.; Zakharov, L.N.; Rheingold, A.L.; Chemistry: A European Journal, 2005, 11, 7328-7341.

Multiple bonding modes exhibited by heteroscorpionate N2S(alkylthiolate) ligands with Zn(II) and Fe(II)
Karambelkar, V.V.; diTargiani, R.C.; Incarvito, C.D.; Zakharov, L.N.; Rheingold, A.L.; Stern, C.L.; Goldberg*, D.P.;
Polyhedron; 2004; 23, 471-480.

Hydrolysis of 4-Nitrophenyl Acetate by a (N2S(thiolate))zinc Hydroxide Complex: A Model of the Catalytically Active Intermediate for the Zinc Form of Peptide Deformylase
diTargiani, R. C.; Chang, S.; Salter, M. H., Jr.; Hancock, R. D.; Goldberg*, D. P.; Inorg. Chem., 2003, 42, 5825-5836.

New Monomeric Cobalt(II) and Zinc(II) Complexes of a Mixed N,S(alkylthiolate) Ligand: Model Complexes of (His)(His)(Cys) Metalloprotein Active Sites
Chang, S.; Karambelkar, V. V.; Sommer, R. D.; Rheingold, A. L.; Goldberg*, D. P.; Inorg. Chem., 2002, 41, 239-248.

A New Bis(imidazolyl)(alkylthiolate) Tripodal L

igand and the Spontaneous Formation of a Disulfide-Linked, Hydroxo-Bridged Dinuclear Zinc Complex
Karambelkar, V.K.; Krishnamurthy, D.; Stern, C.L.; Zakharov, L.N.; Rheingold, A.L.; Goldberg*, D.P.; Chem. Commun.; 2002; 2772-2773.

Model Complexes of the Active Site in Peptide Deformylase: A New Family of Mononuclear N2S-M(II) Complexes
Chang, S.; Karambelkar, V. V.; diTargiani, R. C.; Goldberg*, D. P.; Inorg. Chem.; 2001; 40; 194-195.

A model complex of a possible intermediate in the mechanism of action of peptide deformylase: first example of an (N2S)zinc(II) formate complex
Chang, S.; Sommer, R.D.; Rheingold, A.L.; Goldberg*, D.P.; Chem. Commun.; 2001; 2396-2397.

Slow Magnetic Relaxation of [Et3NH]2[Mn(CH3CN)4(H2O)2][Mn10O4(biphen)4Br12] (biphen = 2,2’-biphenoxide) at Very Low Temperature
Barra, A. L.; Caneschi, A.; Gatteschi, D.; Goldberg, D. P.; Sessoli*, R.J.; Solid State Chem., 1999, 484 - 487.