means that the H2O’s are decreasing the covalency because HOH-S Hydrogen-bonding pulls the sulfur electrons. Since covalency stabilizes Fe3+ more than Fe2+, therefore Fe3+ is more destabilized by the HOH-S hydrogen-bonding. The Fe3+ 3d orbital energies follow the “inverted” bonding scheme which fortuitously has the Fe3+ d-orbitals closely matched in energy with the sulfur 3p orbitals which gives high covalency in the resulting bonding molecular orbital. This high covalency lowers the inner sphere reorganization energy and ultimately contributes to a rapid electron transfer. 2Fe–2S clusters The simplest polymetallic system, the [Fe2S2] cluster, is constituted by two iron ions bridged by two sulfide ions and coordinated by four cysteinyl ligands (in Fe2S2 ferredoxins) or by two cysteines and two histidines (in Rieske proteins). The oxidized proteins contain two Fe3+ ions, whereas the reduced proteins contain one Fe3+ and one Fe2+ ion. These species exist in two oxidation states, (FeIII)2 and FeIIIFeII. CDGSH iron sulfur domain is also associated with 2Fe-2S clusters. 4Fe–4S clusters A common motif features a four iron ions and four sulfide ions placed at the vertices of a cubane-type cluster. The Fe centers are typically further coordinated by cysteinyl ligands. The [Fe4S4] electron-transfer proteins ([Fe4S4] ferredoxins) may be further subdivided into low-potential (bacterial-type) and high-potential (HiPIP) ferredoxins. Low- and high-potential ferredoxins are related by the following redox scheme: In HiPIP, the cluster shuttles between [2Fe3+, 2Fe2+] (Fe4S42+) and [3Fe3+, Fe2+] (Fe4S43+). The potentials for this redox couple range from 0.4 to 0.1 V. In the bacterial ferredoxins, the pair of oxidation states are [Fe3+, 3Fe2+] (Fe4S4+) and [2Fe3+, 2Fe2+] (Fe4S42+). The potentials for this redox couple range from −0.3 to −0.7 V. The two families of 4Fe–4S clusters share the Fe4S42+ oxidation state. The difference in the redox couples is attributed to the degree of hydrogen bonding, which strongly modifies the basicity of the cysteinyl thiolate ligands. A further redox couple, which is still more reducing than the bacterial ferredoxins is implicated in the nitrogenase. Some 4Fe–4S clusters bind substrates and are thus classified as enzyme cofactors. In aconitase, the Fe–S cluster binds aconitate at the one Fe centre that lacks a thiolate ligand. The cluster does not undergo redox, but serves as a Lewis acid catalyst to convert citrate to isocitrate. In radical SAM enzymes, the cluster binds and reduces S-adenosylmethionine to generate a radical, which is involved in many biosyntheses. The second cubane shown here with