Facile and dynamic cleavage of every iron-sulfide bond in cuboidal iron-sulfur clusters

Nature employs weak-field metalloclusters to support a wide range of biological processes. The most ubiquitous metalloclusters are the cuboidal Fe-S clusters, which are comprised of Fe sites with locally high-spin electronic configurations. Such configurations enhance rates of ligand exchange and imbue the clusters with a degree of structural plasticity that is increasingly thought to be functionally relevant. Here, we examine this phenomenon using isotope tracing experiments. Specifically, we demonstrate that synthetic [Fe4S4] and [MoFe3S4] clusters exchange their Fe atoms with Fe2+ ions dissolved in solution, a process that involves the reversible cleavage and reformation of every Fe-S bond in the cluster core. This exchange is facile-in most cases occurring at room temperature on the timescale of minutes-and documented over a range of cluster core oxidation states and terminal ligation patterns. In addition to suggesting a highly dynamic picture of cluster structure, these results provide a method for isotopically labeling pre-formed clusters with spin-active nuclei, such as 57Fe. Such a protocol is demonstrated for the radical S-adenosyl-l-methionine enzyme, RlmN.

Automated summary

Nature uses weak-field metalloclusters to support various biological processes. The most common metalloclusters are cuboidal Fe-S clusters, which consist of Fe sites with locally high-spin electronic configurations. These clusters have enhanced ligand exchange rates and structural plasticity that play functional roles. In this study, isotope tracing experiments show that synthetic [Fe4S4] and [MoFe3S4] clusters can exchange their Fe atoms with Fe2+ ions in solution by cleaving and reforming Fe-S bonds. This exchange occurs rapidly and is documented for a range of cluster core oxidation states and terminal ligation patterns. Additionally, the results demonstrate a method for isotopically labeling pre-formed clusters.