SGER: Bisanthracene-based Mimics of the Hemoglobin Protein

该项目旨在合成和表征基于双蒽的小分子，其具有模仿血红蛋白的合作配体结合特性的能力。这些特性对于血红蛋白呼吸功能的开关式结合至关重要，使肺中的四个氧分子快速饱和，并将这种货物有效，完整地输送到组织。这种协同性是通过机械化学偶联现象介导的Fe-血红素结合位点的相互构象变化来实现的。 将合成一系列旨在模拟这些显着特性的基于双蒽的小分子。这些新的化合物，然后将系统地评估其能力，通过机械化学偶联使用一套变温NMR和X-射线晶体学技术，以配合结合金属离子或分子氧。这些研究的结果将用于设计未来的衍生物，基于相同的双蒽骨架，具有优化的协同氧结合能力。伊利诺伊大学化学系的伯克说。 Burke教授的研究重点是合成和研究具有蛋白质样功能的小分子。 通过这项研究开发的合成方法将对药物，天然产物和材料的制备产生影响。对小分子执行高阶功能的能力的基本理解将使这些化合物在药物应用中更有效地利用，包括用“分子修复术”替代缺失的蛋白质。"

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."