# Low-Coordinate Synthetic Models for Nitrogenase Activity > **NIH NIH R01** · YALE UNIVERSITY · 2021 · $324,027 ## Abstract Project Summary 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 chem... ## Key facts - **NIH application ID:** 10218187 - **Project number:** 5R01GM065313-17 - **Recipient organization:** YALE UNIVERSITY - **Principal Investigator:** PATRICK L HOLLAND - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $324,027 - **Award type:** 5 - **Project period:** 2004-04-01 → 2023-03-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10218187 ## Citation > US National Institutes of Health, RePORTER application 10218187, Low-Coordinate Synthetic Models for Nitrogenase Activity (5R01GM065313-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10218187. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*