The conversion of dinitrogen to ammonia is required for the global nitrogen cycle and is accomplished biologically by nitrogenase enzymes. Although highly inert, dinitrogen is fixed by nitrogenase enzymes, and made biologically available, allowing uptake to form key nutrients necessary to sustain life. The nitrogenase enzyme active site features a multi-metallic core contained within a complex network of amino acids, which are necessary to orchestrate a series of multi-proton, multi-electron transfers during the reduction process. Although crucial for dinitrogen reduction, the precise molecular role that these secondary interactions take to promote reduction is not well known. More explicitly, the scientific community does not precisely know where and how substrates bind, and how electrons are delivered to N2. Thus, there is an inherent gap in our knowledge underlying key contributors to nitrogenase reactivity. To address this gap, this proposal targets the design and study of small molecular constructs that contain highly directed and variable secondary coordination sphere interactions. We will maintain a constant environment within the primary coordination sphere, and modify appended functionality (hydrogen-bond donors/acceptors, Lewis acids/bases) in the secondary coordination sphere environment to evaluate cooperative reactivity. We will use these intermediate structures to test key mechanistic hypotheses regarding the molecular-level reduction of substrates using secondary-sphere cooperativity. We propose that the same type of interactions evaluated in our synthetic systems that promote nitrogenase-type activity can be, by extension, adapted to describe biological systems. The knowledge we acquire will provide key needed contributions to mechanistic studies of nitrogenase function and also synthetic nitrogenases. Substrate activation promoted by highly directed secondary sphere interactions is a broad theme among many biocatalytic cycles, and thus, we envision that the results of our studies will have broad utility to elucidate meaningful contributors to enzymatic reactivity.
All life requires some form of nitrogen to function, and although the atmosphere is comprised of roughly 78% of dinitrogen (N2), it is biologically unavailable without reduction by nitrogenase enzymes, which convert unreactive N2 to a biologically-available form for uptake. The intimate details of this critical (and difficult) transformation are not understood, and although biological studies on the enzyme have demonstrated a critical role of cooperative interactions by nearby amino acid residues and a multi-metallic enzyme core, we do not know the intimate molecular details. This project aims to develop a molecular level understanding of these cooperative effects on substrate activation, which in addition to contributing important mechanistic details that govern nitrogenase function, may also translate into new catalyst development for organic and inorganic transformations.
| Dahl, E W; Dong, H T; Szymczak, N K (2018) Phenylamino derivatives of tris(2-pyridylmethyl)amine: hydrogen-bonded peroxodicopper complexes. Chem Commun (Camb) 54:892-895 |
| Dahl, Eric W; Kiernicki, John J; Zeller, Matthias et al. (2018) Hydrogen Bonds Dictate O2 Capture and Release within a Zinc Tripod. J Am Chem Soc 140:10075-10079 |
| Kiernicki, John J; Zeller, Matthias; Szymczak, Nathaniel K (2017) Hydrazine Capture and N-N Bond Cleavage at Iron Enabled by Flexible Appended Lewis Acids. J Am Chem Soc 139:18194-18197 |
| Geri, Jacob B; Shanahan, James P; Szymczak, Nathaniel K (2017) Testing the Push-Pull Hypothesis: Lewis Acid Augmented N2 Activation at Iron. J Am Chem Soc 139:5952-5956 |
| Hale, Lillian V A; Szymczak, Nathaniel K (2016) Stereoretentive Deuteration of ?-Chiral Amines with D2O. J Am Chem Soc : |
| Dahl, Eric W; Szymczak, Nathaniel K (2016) Hydrogen Bonds Dictate the Coordination Geometry of Copper: Characterization of a Square-Planar Copper(I) Complex. Angew Chem Int Ed Engl 55:3101-5 |
