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 [Fe(4)S(4)] and [MoFe(3)S(4)] clusters exchange their Fe atoms with Fe(2+) 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 (57)Fe. Such a protocol is demonstrated for the radical S-adenosyl-l-methionine enzyme, RlmN.