Title: Ligand effects on reactivity of hydride-decorated and reduced multi-iron compounds Abstract Metal cluster cofactors provide substrates with many potential orientations to bind and subsequently undergo chemical transformations. This is particularly true for cluster cofactors that activate small molecule substrates. The focus of this proposal is on the chemistry of the iron-molybdenum cofactor in the molybdenum-dependent nitrogenases, which catalyzes the eight electron and eight proton reduction of dinitrogen and two protons to generate two equivalents of ammonia and one of dihydrogen. The current mechanism proposed for the conversion of N2 to NH3 by this enzyme uses concepts that are common to numerous other metal cofactors, such as the protonation of bridging sulfide donors, the use of metal hydrides to store reducing equivalents, and the potential to coordinate the hydrides and dinitrogen in either terminal or bridging modes. How the iron-molybdenum cofactor binds hydride donors and dinitrogen, as well as intermediates during the catalytic reaction, are fundamental aspects of the mechanism but remain unclear. This is the knowledge gap that this proposal addresses. This proposal will accomplish this goal by using synthetic clusters in which substrates (hydrides and dinitrogen) can bind in either bridging or terminal coordination modes, which mirrors the coordinative flexibility possible for these substrates on the iron-molybdenum cofactor. As part of this inquiry, this proposal will dissect how number, identity, and connectivity of bridging ligands modulate substrate coordination. The results generated in this proposal have broader implications for biochemical reactions, and specifically, shed light on the principles that govern biological catalysis of multi-electron multi-proton redox reactions (e.g., water oxidation in photosynthesis, dioxygen reduction in respiration).
This research develops a new approach to understanding how structure and composition of iron clusters dictates reactivity. This proposal specifically addresses the challenging six-electron six-proton reduction of atmospheric nitrogen to ammonia by the iron-molybdenum cofactor in molybdenum-dependent nitrogenases. Ammonia is a building block in the synthesis of value-added chemicals including pharmaceuticals; however, the major impact of this proposal is that it will elucidate the parameters that determine how biological systems catalyze multi-electron multi-proton redox reactions. These reactions are vital for global element cycles, and underpin fundamental processes, such as respiration and photosynthesis.
| Cook, Brian J; Di Francesco, Gianna N; Ferreira, Ricardo B et al. (2018) Chalcogen Impact on Covalency within Molecular [Cu3(?3-E)]3+ Clusters (E = O, S, Se): A Synthetic, Spectroscopic, and Computational Study. Inorg Chem 57:11382-11392 |
| Ferreira, Ricardo B; Cook, Brian J; Knight, Brian J et al. (2018) Catalytic Silylation of Dinitrogen by a Family of Triiron Complexes. ACS Catal 8:7208-7212 |
