Metal-metal bonds in biology

Abstract

Nickel-containing carbon monoxide dehydrogenases, acetyl-CoA synthases, nickel-iron hydrogenases, and diron hydrogenases are distinct metalloenzymes yet they share a number of important characteristics. All are O(2)-sensitive, with active-sites composed of iron and/or nickel ions coordinated primarily by sulfur ligands. In each case, two metals are juxtaposed at the "heart" of the active site, within range of forming metal-metal bonds. These active-site clusters exhibit multielectron redox abilities and must be reductively activated for catalysis. Reduction potentials are milder than expected based on formal oxidation state changes. When reductively activated, each cluster attacks an electrophilic substrate via an oxidative addition reaction. This affords a two-electron-reduced substrate bound to one or both metals of an oxidized cluster. M-M bonds have been established in hydrogenases where they serve to initiate the oxidative addition of protons and perhaps stabilize active sites in multiple redox states. The same may be true of the CODH and ACS active sites-Ni-Fe and Ni-Ni bonds in these sites may play critical roles in catalysis, stabilizing low-valence states and initiating oxidative addition of CO(2) and methyl group cations, respectively. In this article, the structural and functional commonalities of these metalloenzyme active sites are described, and the case is made for the formation and use of metal-metal bonds in each enzyme mentioned. As a post-script, the importance of Fe-Fe bonds in the nitrogenase FeMoco active site is discussed.

Figure 1

Structures of oxidized active sites that are hypothesized to possess M-M bonds when reduced.

Figure 2

Formation of MM dative bonds. In this hypothetical example, a divalent donor metal is located near to the acceptor metal. The ligand environment supports redox-activity of the donor but not the acceptor. A two electron reduction is coupled to the formation of a dative bond. The two metals move together slightly and a water/hydroxide that had bridged the two metal ions dissociates. Once formed, the dative bond can initiate oxidative addition chemistry by reacting with an electrophile. After reacting, the reduced electrophile is bound to the donor metal which has become reoxidized, and an hydroxide ion coordinates the other site. In other cases, the electrophile might bridge the metals.

Figure 3

NiFe hydrogenase model complexes (top, from [26]) and catalytic mechanism (bottom), emphasizing the role of Ni-Fe bonds.

Figure 4

[FeFe] hydrogenase mechanism, emphasizing the role of Fe-Fe bonds.

Figure 5

CODH mechanism, emphasizing the role of the Ni-Fe bond.

Figure 6

ACS model complexes (top) and catalytic mechanism (bottom). Both complexes are from [59].