# Inserting carbide in ligand templated iron-sulfur clusters and their reactivity towards hydrides and N2 > **NIH NIH F32** · YALE UNIVERSITY · 2021 · $66,390 ## Abstract PROJECT SUMMARY Nitrogenases provide nearly all bioavailable nitrogen by catalytically reducing N2 to produce NH3. The active site for N2 reduction is an iron-molybdenum cofactor (MoFe7S9C, or FeMoco) that features high-spin iron centers bridged by sulfide (S2−) and an intriguing carbide (C4−) that bridges six iron centers. This biologically unprecedented carbide ligand raises questions concerning its mechanism of insertion into FeMoco. The carbide originates from a methyl group transferred to an iron-sulfur cluster by a S-adenosylmethionine (SAM) enzyme. However, the mechanisms that convert this methyl group into the final interstitial carbide, and the intermediates along the way, remain unknown. The fact that natural systems insert this carbide into nitrogenases also leads to questions about the structural and electronic impact of carbide on the reactivity of FeMoco. A primary aim of this proposal is to study carbide insertion in iron-sulfur clusters to understand what chemically feasible intermediates may be relevant to the biosynthesis of FeMoco. While studying the biosynthesis of FeMoco is difficult in the native enzyme, model clusters provide us synthetic control over specific structural and electronic factors to systematically test our hypotheses. Our main strategy is to design and synthesize scaffold ligands that can template trinuclear iron clusters featuring only sulfur donors. The sulfur donors will yield high-spin, coordinately unsaturated iron sites that mimic iron's coordination environment in FeMoco. We propose to install methyl (CH3), carbene (CH2), carbyne (CH), and carbide (C) ligands in the iron- sulfur clusters and study the interconversion between these compounds. These species are proposed intermediates during the biosynthesis of FeMoco, and the interconversion between these clusters will inform us what chemical transformations are feasible during the biosynthesis of FeMoco. Finally, we aim to explore N2 binding by iron-sulfur clusters. We propose that these are best accessed from hydride-bridged iron-sulfur clusters, in a biomimetic mechanism that will help to elucidate the ability of H2 elimination for enabling N2 binding. We will install hydride ligands on these biomimetic clusters and exploit reductive elimination of H2 to enable N2 binding. This process mimics the E4 intermediate during N2 reduction by FeMoco. These studies will advance our fundamental understanding of key intermediates and mechanisms during N2 reduction in FeMoco. My training in the Holland group will expand my technical research aptitudes, mentorship, and critical writing and presentation skills. Yale's collection of leading bioinorganic and synthetic inorganic chemists renders it an ideal setting for gaining skills in bioinorganic chemistry, ligand design and synthesis, and mechanistic studies. ## Key facts - **NIH application ID:** 10226067 - **Project number:** 5F32GM136179-02 - **Recipient organization:** YALE UNIVERSITY - **Principal Investigator:** Majed Fataftah - **Activity code:** F32 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $66,390 - **Award type:** 5 - **Project period:** 2020-08-01 → 2023-07-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10226067 ## Citation > US National Institutes of Health, RePORTER application 10226067, Inserting carbide in ligand templated iron-sulfur clusters and their reactivity towards hydrides and N2 (5F32GM136179-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10226067. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*