CYTOCHROME OXIDASE AND H-BONDED OXYHEMOGLOBIN MODELS

提出了将综合模型方法应用于细胞色素氧化酶的研究 和氧合血红蛋白，以获得分子水平的了解， 与氧相互作用时的基本活性部位化学。 合成化学涉及制备超结构的 具有附加的苯并咪唑部分的卟啉， 非常接近血红素铁 具有附加物的栅栏型卟啉 含有H-键合部分的分子将量化远端 氧合血红蛋白模型中氢键对氧合血红蛋白的亲和力有影响。 也是 提出生长有序氧合血红蛋白模型的单晶， 这是第一次，精确的尺寸的FeO 2部分，可以 得到了 所有研究的重点将放在确定的 用X射线表征分析纯晶体材料 结晶学 光谱研究（IR、UV-VIS、EPR、 穆斯堡尔等）还将使用磁化率测量 来表征材料。 这些化合物将提供明确的系统 在此基础上测试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。 模型化合物将用于 深入了解血红素蛋白与氧相互作用的机制。 在分子水平上对血红素蛋白的详细了解， 治疗其疾病（地中海贫血、镰状贫血）的医疗方法 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.).