The expanding utility of iron-sulfur clusters: Their functional roles in biology, synthetic small molecules, maquettes and artificial proteins, biomimetic materials, and therapeutic strategies

The ubiquity, structural variation, and functional diversity of iron-sulfur (Fe-S) clusters in biological environments has long fascinated scientists. In nature, Fe-S clusters form a variety of shapes and sizes, from the simple [Fe2S2] rhombic cluster to the complex [Fe8S7] fused di-cubane ‘P-cluster’, among others. Fe-S clusters perform critical tasks, including electron transfer, catalysis, sulfur donation, and sensing, in many essential biological processes, such as cellular respiration, gene expression, nitrogen fixation, DNA repair, cofactor biosynthesis, and more. To further understand Fe-S clusters, they have been synthesized outside of their protein environments with various monodentate, bidentate, and tridentate ligands. In addition to providing insight into their biological properties, synthetic small molecule models of Fe-S clusters have yielded oxidation states and structures beyond those observed in biology as well as led to the development of many small molecule catalysts. More recently, Fe-S clusters have been utilized in an expanding array of applications, including maquettes and artificial proteins, biomimetic materials, and therapeutic development. The high degree of utility of Fe-S clusters outside of their biological roles suggests exciting possibilities for future uses of these earth-abundant, redox-active, and structurally and functionally diverse clusters. This review provides an overview of Fe-S clusters in and beyond biology to highlight the growing versatile uses of these clusters. Our discussion is divided into sections that describe the structure–function relationship of Fe-S clusters in five research areas: biology, synthetic small molecules, maquettes and artificial proteins, biomimetic materials, and therapeutic development. We also tracked the number of publications in each research area by year to identify trends in Fe-S cluster research, and we conclude by describing the overarching connections between each of the research areas. Overall, this review summarizes the application areas of Fe-S cluster research and highlights connections between the areas based on the structure–function relationship of Fe-S clusters and their ligands.