SGER: Bisanthracene-based Mimics of the Hemoglobin Protein

本项目旨在合成和表征具有模拟血红蛋白协同配体结合特性的双茂铁基小分子。这些特性对其作为血红蛋白呼吸功能基础的开关状结合至关重要，使其能够与肺部的四个氧分子快速饱和，并高效、完整地将这些货物运送到组织中。这种协作性是通过机械力化学耦合现象介导的铁-血红素结合部位的往复构象变化实现的。将合成一系列旨在模拟这些显着性质的双茂铁基小分子。然后，利用一套变温核磁共振和X射线结晶学技术，系统地评估这些新化合物通过机械力化学耦合作用与金属离子或分子氧协同结合的能力。这些研究的结果将被用来设计未来的衍生物，基于相同的双菲骨架，具有优化的合作氧结合能力。通过这个奖项，有机和高分子化学计划支持伊利诺伊大学化学系的马丁·D·伯克教授的研究。伯克教授的研究重点是具有类似蛋白质功能的小分子的合成和研究。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了解将使此类化合物在医药应用中得到更有效的利用，包括用“分子假体”取代缺失的蛋白质。

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."