Synthetic heme protein models that function in aqueous solution
Synthetic heme protein models that function in aqueous solution
复制标题
在水溶液中发挥作用的合成血红素蛋白模型
DOI：
10.1039/d0cc07044k
复制
发表时间：
2021
影响因子：
4.9
通讯作者：
Kano Koji
中科院分区：
文献类型：
--
作者：
Kitagishi Hiroaki;Kano Koji
肌红蛋白（Mb）被认为是自然条件下捕获水溶液中分子氧（O2）的最佳体系。因此，制备模拟Mb功能的人工系统是一个长期存在且具有挑战性的目标。人们设计并合成了各种结构复杂的铁卟啉化合物，以实现其轴向位置的氧结合。虽然所有这些化合物可逆地结合O2在绝对有机溶剂中，没有稳定的O2加合物在水溶液中得到。其原因是O2加合物被水分子立即自氧化。为了在水溶液中实现O2结合，卟啉的铁中心必须置于疏水环境中，其中严格排除水分子。Mb模型的另一个基本要求是制备起近端组氨酸（His）作用的电子供体轴向配体。作为满足这些挑战性要求的人工O2受体，已经构建了称为“hemoCD 1”的超分子。HemoCD 1是5，10，15，20-四（4-磺酸基苯基）卟啉铁（II）（FeIITPPS）与带有吡啶连接体的全-O-甲基化β-环糊精二聚体（Py 3CD）的1：1包合物，在中性pH和环境温度下，在水溶液中可逆结合O2。 电子光谱以及功能的hemoCD 1是类似的Mb或其四聚体，血红蛋白（Hb）。这是能够在水溶液中起作用的人工Hb/Mb仿生模型的第一个实例。对作为Hb/Mb模型的hemoCD 1的这种研究已经将研究目标扩展到（1）具有不同特征的hemoCD 1类似物的合成，（2）模拟过氧化物酶、血红素加氧酶和细胞色素c氧化酶在水中的酶促反应，（3）开发用于动物血液的全合成人工氧载体（AOC），和（4）选择性结合和去除有毒小分子，例如生物体内的一氧化碳（CO）和氰化物（CN-）。
Myoglobin (Mb) is considered as the optimal system for capturing molecular oxygen (O2) in aqueous solution under natural conditions. Therefore, the preparation of artificial systems that mimic the function of Mb is a long-standing and challenging objective. Various sophisticated iron porphyrins have been designed and synthesized to realize O2 biding at their axial positions. Although all of these compounds reversibly bind O2 in absolute organic solvents, no stable O2 adducts were obtained in aqueous solution. The reason for this is the immediate autoxidation of O2 adducts by water molecules. To achieve O2 binding in aqueous solution, the iron center of the porphyrin must be placed in a hydrophobic environment, wherefrom a water molecule is strictly excluded. Another essential requirement for a Mb model is the preparation of an electron-donative axial ligand that plays the role of proximal histidine (His). As an artificial O2 receptor that satisfies these challenging requirements, a supramolecule termed “hemoCD1” has been constructed. HemoCD1, a 1 : 1 inclusion complex of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphinatoiron(II) (FeIITPPS) with a per-O-methylated β-cyclodextrin dimer bearing a pyridine linker (Py3CD), reversibly binds O2 in aqueous solution at neutral pH and ambient temperature. The electronic spectra as well as the functions of hemoCD1 are analogous to those of Mb or its tetramer, hemoglobin (Hb). This is the first example of an artificial Hb/Mb biomimetic model capable of function in aqueous solution. Such a study on hemoCD1 as a Hb/Mb model has expanded research objectives to (1) syntheses of hemoCD1 analogues having distinct characteristics, (2) modeling enzymatic reactions of peroxidase, heme oxygenase, and cytochrome c oxidase in water, (3) development of fully synthetic artificial oxygen carriers (AOCs) utilized in animal blood, and (4) selective binding and removal of toxic small molecules, such as carbon monoxide (CO) and cyanide (CN−) in living organisms.