Metal–metal bonds in biology

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 O2-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 CO2 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.

The possibility that metal–metal bonds form in metalloenzymes and are used in catalysis is highlighted using iron–iron hydrogenase, nickel–iron hydrogenase, nickel-containing carbon monoxide dehydrogenase, acetyl-coenzyme A synthase and nitrogenase as examples. These bonds are proposed to form in reduced states and function to initiate oxidative addition reactions. If verified, a new motif in mechanistic bioinorganic chemistry would be established.Figure optionsDownload as PowerPoint slide