Reversible Alkyl-Group Migration between Iron and Sulfur in [Fe₄S₄] Clusters

Synthetic [Fe₄S₄] clusters with Fe-R groups (R = alkyl/benzyl) are shown to release organic radicals on an [Fe₄S₄]³⁺-R/[Fe₄S₄]²⁺ redox couple, the same that has been proposed for a radical-generating intermediate in the superfamily of radical S-adenosyl-l-methionine (SAM) enzymes. In attempts to trap the immediate precursor to radical generation, a species in which the alkyl group has migrated from Fe to S is instead isolated. This S-alkylated cluster is a structurally faithful model of intermediates proposed in a variety of functionally diverse S transferase enzymes and features an "[Fe₄S₄]⁺-like" core that exists as a physical mixture of S = 1/2 and 7/2 states. The latter corresponds to an unusual, valence-localized electronic structure as indicated by distortions in its geometric structure and supported by computational analysis. Fe-to-S alkyl group migration is (electro)chemically reversible, and the preference for Fe vs S alkylation is dictated by the redox state of the cluster. These findings link the organoiron and organosulfur chemistry of Fe-S clusters and are discussed in the context of metalloenzymes that are proposed to make and break Fe-S and/or C-S bonds during catalysis.