This project aims to synthesize and characterize bis-anthracene-based small molecules with the capacity to mimic the cooperative ligand binding properties of the hemoglobin protein. These properties are critical to its switch-like binding that underlies hemoglobin's respiratory function, enabling rapid saturation with four molecules of oxygen in the lungs and efficient, complete delivery of this cargo to the tissues. This cooperativity is achieved via reciprocated conformational changes at the Fe-heme binding sites mediated via the phenomenon of mechanochemical coupling. A series of bis-anthracene-based small molecules designed to mimic these remarkable properties will be synthesized. These novel compounds will then be systematically evaluated for their capacity to cooperatively bind metal ions or molecular oxygen via mechanochemical coupling using a suite of variable temperature NMR and X-ray crystallographic techniques. The results of these studies will be used to design future derivatives, based on the same bis-anthracene skeleton, with optimized capacity for cooperative oxygen binding.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Martin D. Burke of the Department of Chemistry at the University of Illinois. Professor Burke's research efforts are focused on the synthesis and study of small molecules with the capacity to perform protein-like functions. The synthetic methods developed through this research will have an impact on the preparation of pharmaceuticals, natural products, and materials. The fundamental understanding of the capacity of small molecules to perform higher-order functions will enable the more effective utlilization of such compounds in pharmaceutical applications, including the replacement of missing proteins with "molecular prosthetics."
