Biological reduction of N2 to NH3 is performed solely by nitrogenase enzymes, which have unusual iron- sulfide-carbide clusters as active sites. We focus here on the FeMoco cofactor in iron-molybdenum nitrogenase, which accomplishes this multielectron catalytic reaction through an unknown mechanism. The FeMoco is the only example of a carbide (formally C4?) in biological chemistry. This carbide is presumably inserted by way of Fe-CH3, Fe-CH2, and Fe-CH intermediates that are unprecedented in iron-sulfide compounds. The unusual coordination chemistry in the FeMoco presumably contributes to its ability to reduce N2, but the lack of precedents for the putative species in the biosynthetic and catalytic pathways hinders the ability to evaluate whether the proposed mechanisms are reasonable. Similarly, the interpretation of spectroscopic data is difficult because of the lack of related compounds in the literature. Moving the field forward requires new coordination chemistry that elucidates the properties and reactivity of relevant clusters. Our guiding hypothesis is that synthetic FeS and FeC clusters with bulky supporting ligands will have structural, spectroscopic, and reactivity attributes of activated FeMoco. Because these clusters have environments that are known unambiguously, they can establish the spectroscopic signatures of specific structural features, which links structure and spectroscopy firmly. In addition, they can be used to test the feasibility of mechanistic steps such as Fe-C bond cleavage, Fe-S bond cleavage, and Fe-N2 bond formation. In the proposed research, we will synthesize new cluster compounds with iron-sulfur and iron-carbon cores. One focus is iron-sulfide clusters that can bind N2 and other nitrogenase substrates. We will prepare the first iron-sulfide clusters that bind N2, and will explore their spectroscopic properties and reactions. A second focus is on a systematic series of compounds with Fe-C bonds having different numbers of hydrogen atoms, and culminating in carbide-bridged clusters. We propose that comparison of iron methyl, carbene, carbyne, and carbide compounds will elucidate the fundamentals of different Fe-C bonds in high-spin iron clusters resembling the FeMoco. Addition and removal of hydrogen atoms interconverts these species, mimicking steps in the biosynthesis of the FeMoco. The formation and cleavage of Fe-C bonds in the compounds is also relevant to the mechanism of nitrogenase activity, and will be addressed using reactivity and spectroscopic studies. Collaborations with leading spectroscopists who work on nitrogenase enhances the relevance and rigor of our comparisons to the enzyme. Nitrogenase is amazing because it carries out a thermodynamically demanding multielectron reduction, it possesses a unique cofactor structure with a carbide, and it has the rare ability to interact with N2. However, linking and understanding these observations requires advances in the fundamental chemistry of FeS clusters. This project will provide the chemical precedents that are needed to comprehend the FeMoco.
The enzyme nitrogenase converts atmospheric nitrogen into ammonia, a process that is essential for life on Earth. Nitrogenase accomplishes this crucial reaction at the FeMoco, a cluster of iron, sulfur, and carbon with an unprecedented structure. We propose to make new cluster molecules that reproduce different attributes of the FeMoco cluster, thus illuminating the fundamental chemistry underlying nitrogen reduction in nature.
| McWilliams, Sean F; Bunting, Philip C; Kathiresan, Venkatesan et al. (2018) Isolation and characterization of a high-spin mixed-valent iron dinitrogen complex. Chem Commun (Camb) 54:13339-13342 |
| Broere, Daniel L J; Mercado, Brandon Q; Bill, Eckhard et al. (2018) Alkali Cation Effects on Redox-Active Formazanate Ligands in Iron Chemistry. Inorg Chem 57:9580-9591 |
| Broere, Daniël L J; Holland, Patrick L (2018) Boron compounds tackle dinitrogen. Science 359:871 |
| Skubi, Kazimer L; Holland, Patrick L (2018) So Close, yet Sulfur Away: Opening the Nitrogenase Cofactor Structure Creates a Binding Site. Biochemistry 57:3540-3541 |
| DeRosha, Daniel E; Holland, Patrick L (2018) Incorporating light atoms into synthetic analogues of FeMoco. Proc Natl Acad Sci U S A 115:5054-5056 |
| Broere, Daniël L J; Mercado, Brandon Q; Lukens, James T et al. (2018) Reversible Ligand-Centered Reduction in Low-Coordinate Iron Formazanate Complexes. Chemistry 24:9417-9425 |
| Broere, Daniël L J; Mercado, Brandon Q; Holland, Patrick L (2018) Selective Conversion of CO2 into Isocyanate by Low-Coordinate Iron Complexes. Angew Chem Int Ed Engl 57:6507-6511 |
| Chen, Jingguang G; Crooks, Richard M; Seefeldt, Lance C et al. (2018) Beyond fossil fuel-driven nitrogen transformations. Science 360: |
| McWilliams, Sean F; Bill, Eckhard; Lukat-Rodgers, Gudrun et al. (2018) Effects of N2 Binding Mode on Iron-Based Functionalization of Dinitrogen to Form an Iron(III) Hydrazido Complex. J Am Chem Soc 140:8586-8598 |
| Pelmenschikov, Vladimir; Gee, Leland B; Wang, Hongxin et al. (2018) High-Frequency Fe-H Vibrations in a Bridging Hydride Complex Characterized by NRVS and DFT. Angew Chem Int Ed Engl 57:9367-9371 |
Showing the most recent 10 out of 72 publications
