Climate change is one of the greatest global challenges of our century. Industrial fertilizer and fuel production by Haber-Bosch (HB) and Fischer-Tropsch (FT) processes are extremely energy-intensive, with HB alone emitting 500M tons of carbon dioxide annually. In contrast, microbial metalloenzymes achieve the same chemical transformations sustainably: vanadium nitrogenase (active site denoted as FeVco) converts nitrogen to ammonia, and carbon monoxide (CO) to fuels under ambient conditions, without harmful byproducts. However, this remarkable enzyme remains underexplored, and its catalytic mechanism is unclear. My research aims to elucidate the substrate-specific mechanism of FeVco using a synergistic combination of hybrid quantum mechanical/molecular mechanical (QM/MM) simulations, advanced multireference electronic structure methods, and spectroscopic tools (EPR, XAS). In this talk, I will focus on our efforts to determine the ground spin and oxidation states of FeVco, which play a central role in governing substrate binding and reaction pathways. By systematically analyzing 35 broken-symmetry solutions using density functional theory, we characterize the geometric and energetic features of the resting state and the E1 intermediate, formed upon the addition of a proton and an electron. We further identify the most likely protonation sites in the E1 state, providing new mechanistic insight and enabling direct comparison with molybdenum and iron-only nitrogenases. A detailed understanding of vanadium nitrogenase would ultimately guide the rational design of bio-inspired catalysts for sustainable fertilizer and fuel production, offering alternatives to the energy-intensive HB and FT processes.
Dr. Vyshnavi Vennelakanti