Prof. Daniel Suess

Researchers in the Suess Lab tackle problems at the interface of inorganic and biological chemistry. Many of the reactions that underlie fundamental life processes are catalyzed by metals found in the active sites of metalloenzymes. Some metalloenzyme active sites feature only a single metal ion, but hundreds of thousands feature polynuclear metallocofactors—clusters of multiple metal ions that work cooperatively to maximize catalytic efficiency and/or to achieve reactivity not possible at a single metal. Of such polynuclear metallocofactors, iron-sulfur clusters are the most ubiquitous; they are found in all kingdoms of life and are as old as life itself. They play a central role in health and metabolism and are constantly reshaping the molecular composition of the biosphere. And their reaction chemistry is as diverse as their functions: iron-sulfur clusters catalyze some of the most demanding reactions, such as the conversion of inert dinitrogen to ammonia fertilizer, as well as simpler electron-transfer reactions that support photosynthesis, respiration, and DNA repair. Given their prominent role in all facets of life, my research group studies the reaction mechanisms of iron-sulfur clusters, with a particular focus on revealing the fundamental chemical bonding that gives rise to their unusual reactivity.

The unifying goal of our research is to understand the nature of the iron-iron and iron-sulfur interactions in iron-sulfur clusters, the physical properties that emerge therefrom, and how these physical properties contribute to the reaction chemistry of iron-sulfur clusters. We study both synthetic iron-sulfur clusters -- those produced in the laboratory -- as well as biogenic clusters, produced in the cell. By working at this synthetic/biological interface, we forge deep connections between the properties and reactivity/functions of iron-sulfur clusters.

The assembly and study of synthetic iron-sulfur clusters has been an active area of research since Richard H. Holm’s pioneering work beginning more than fifty years ago. My lab uses this as a foundation for our research by employing known protocols for assembling iron-sulfur clusters and subsequently building a protective environment around the clusters. Doing so stabilizes the cluster, allows for binding and activation of inert substrates, and affords exquisite control over the cluster’s geometric and electronic structures. We are thereby able to generate and fully characterize clusters in unusual bonding modes and to form and test hypotheses about their physical properties and reaction chemistry. This work simultaneously informs how iron-sulfur enzymes operate and provides insight into how catalysts based on these motifs can be developed outside of biology.

In the work on biogenic iron-sulfur clusters, we develop novel methods for obtaining synthetic-chemistry-like control over their composition. In particular, we incorporate spectroscopically useful isotopes into only one metal site out of the many sites in the cluster. We thereby obtain insights into the chemical bonding at the labeled site and thus can connect the chemical bonding at the labeled site to the geometric structure of the cluster. This approach also simplifies spectroscopic analysis, making these complex cofactors as tractable as mononuclear iron complexes because, as for a mononuclear complex, only a single iron is isotopically labeled. In this work we have initially targeted some of the most structurally and mechanistically complex iron-sulfur clusters: the nitrogenase cofactors, which perform the life-sustaining conversion of dinitrogen to ammonia. This work therefore provides new insights into how Nature fixes nitrogen from air.

Overall, by integrating synthetic and biological inorganic chemistry, my lab reveals the ways in which iron-sulfur clusters have shaped and continue to shape the planet. We anticipate that our methods will shed light on the mechanisms of a wide range of iron-sulfur enzymes and that the principles delineated from this work can be applied beyond biology.