Stepwise and reversible assembly of [2Fe-2S] rhombs to [8Fe-8S] clusters and their topological interconversions

Among all enzymatic metallocofactors, those found in nitrogenases, the P and L or M clusters, stand out for their intricate structures. They are assembled by proteins of the Nif gene cluster from Fe₂S₂ rhombs-the smallest building blocks in FeS cluster chemistry-through a sequence of reactions constructing a Fe₈S₈ precursor. To advance our understanding of how enzymes selectively build such elaborate inorganic molecules, here we parallel the biosynthetic pathway by reporting the rational stepwise assembly of [Fe₈S₈]^m+ (m = 2, 4, 6) clusters from [Fe₂S₂]²⁺ rhombs within an extensive cyclic synthetic network. A [Fe₈S₈]⁴⁺ cluster of unique topology is identified, for which we coin the term 'interlocked' double cubane. As a molecular analogue of the NifB K cluster, a proposed precursor to both the P and L or M clusters, its preparation and the characterization of all related intermediates, offers fundamental insights into the molecular mechanisms governing the assembly of both biogenic and synthetic FeS clusters.