CYTOCHROME OXIDASE AND H-BONDED OXYHEMOGLOBIN MODELS

建议将合成模型方法应用于细胞色素氧化酶研究。 和氧合血红蛋白，以便在分子水平上了解它们 与氧相互作用时的基本活性中心化学。 合成化学涉及超结构化合物的制备。 含苯并咪唑基团的卟啉与铜的结合 靠近亚铁血红素。带附属物的栅栏型卟啉 含有氢键部分将量化远端的贡献 在氧合血红蛋白模型中，氢键可以促进O2的亲和力。它也是 提出了生长有序氧合血红蛋白模型的单晶，以便 第一次，FeO2部分的准确尺寸可以 获得。所有研究的重点都将放在确定的 分析纯晶体材料的X射线表征 结晶学。光谱分析(IR、UV-Vis、EPR、 穆斯堡尔等)磁化率测量也将使用 以确定材料的特性。这些化合物将提供定义明确的体系 用来检验最近关于结构的推论的有效性 细胞色素氧化酶和氧合血红蛋白。模型化合物将被用于 深入了解血红蛋白与氧气相互作用的机制。 对血红蛋白的详细分子水平的了解必须奠定基础 治疗他们疾病(地中海贫血、镰刀状贫血)的医学方法 细胞性贫血等)。

It is proposed to apply the synthetic model approach to cytochrome oxidase and oxyhemoglobin in order to gain a molecular level understanding of their fundamental active site chemistry upon interaction with oxygen. The synthetic chemistry involves the preparation of superstructured porphyrins having appended benzimidazole moieties for binding copper in close proximity to heme iron. Picket-fence-type porphyrins with appendages containing H-bonding moieties will quantify the contribution that a distal H-bond can make to the affinity of O2 in oxyhemoglobin models. It is also proposed to grow single crystals of an ordered oxyhemoglobin model so that for the first time, accurate dimensions of the FeO2 moiety can be obtained. Emphasis in all of the studies will be placed on the definitive characterization of analytically pure crystalline materials by X-ray crystallography. Spectroscopist investigations (IR, UV-VIS, EPR, Mossbauer, etc.) and magnetic susceptibility measurements will also be used to characterize materials. The compounds will provide well-defined systems on which to test the validity of recent deductions about the structure of cytochrome oxidase and oxyhemoglobin. The model compounds will be used to gather insight into the mechanisms of hemoprotein interaction with oxygen. A detailed molecular level understanding of hemoproteins must underlie medical approaches to the therapy of their disorders (thalassemias, sickle cell anemia, etc.).