Designing Polymetallic Clusters to Model the Active site of the FeMo-Cofactor

Harvard University, Cambridge MA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Polymetallic metalloenzymes gate many of the reactions in nature which incorporate oxygen, nitrogen and many other elements essential for life on this planet. Dinitrogen reduction is achieved in nature by the polynuclear metalloenzyme nitrogenase. The site for substrate reduction consists of the MoFe7S7-cofactor. Despite good structural information about the cofactor, many questions regarding substrate binding and the overall chemical action of the cofactor during turnover remain largely unanswered. Functional models for nitrogenase often employ single transition metal ions in ligand environments that do not faithfully reproduce the naturally occurring enzyme sites. Utilizing new methodology to reliably synthesize polymetallic clusters, we seek to employ well-defined trimetallic clusters as building blocks to assemble a cofactor core mimic. Using chemical functionalities found within the native enzyme, polyamine/sulfide ligand systems are proposed as scaffolds to support the tri-iron cores. More importantly, the well-defined molecular tri-iron units will allow us to systematically examine the reaction chemistry of nitrogenase substrates with an iron-only reaction site, as well as synthesize structural mimics of the cofactor with differing interstitial atom components. This proposal seeks to develop polymetallic clusters to both structurally and functionally model the FeMo-cofactor of nitrogenase. PUBLIC HEALTH RELEVANCE: Polymetallic metalloenzymes gate many of the reactions in nature which incorporate oxygen, nitrogen and many other elements essential for life on this planet. Modeling these processes using synthetic bioinorganic chemistry provides us a powerful tool for understanding their structure and function - ultimately yielding chemical insights into biology. This proposal seeks to develop polymetallic clusters to both structurally and functionally model one such reaction center - the FeMo-cofactor of nitrogenase.