Dioxygen binding to a simple myoglobin model in aqueous solution
Dioxygen binding to a simple myoglobin model in aqueous solution
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DOI：
10.1002/anie.200461609
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Hirota, S
中科院分区：
文献类型：
--
作者：
Kano, K;Kitagishi, H;Hirota, S
在这里，我们报道了一个简单的肌红蛋白模型体系的可逆氧结合，该模型体系由一个带有吡啶连接基的全O-甲基化β-环糊精(CD)二聚体(1)和[四(4-磺基)苯基]铁(II)([FeII(TPPS)])组成。肌红蛋白(Mb)和血红蛋白(Hb)在中性pH值的水溶液中形成稳定的O2加合物。珠蛋白在稳定生物系统中的O2加合物方面起着至关重要的作用。如果没有这种蛋白质，氧合血红素会在质子或氢氧化物离子的作用下立即氧化为甲硫氨酸形式。[1]血红素受到围绕铁卟啉(FePor)的珠蛋白的保护，使其不受酸或碱诱导的自氧化。在Collman等人开发了尖桩栅栏卟啉之后，许多Mb和Hb的模型体系被检验。[2，3]在大多数模型体系中，O2结合是在有机溶剂中实现的，其中必须从体系中去除微量的水。科尔曼S研究小组提出的概念已经扩展到O2与疏水的尖桩栅栏FeII卟啉的结合，这些卟啉存在于水介质中的小泡[4]或白蛋白[5]中。虽然具有FeIIPor核的树状大分子被期望模拟Mb或Hb的功能，但在这些体系中在水溶液中没有形成稳定的O2加合物。[6，7]由于树枝状大分子的O2加合物在绝对甲苯中有效地形成，[6]很明显，构建一个疏水口袋来放置FePor的铁(II)中心是实现水溶液中O2结合的关键因素。在本模型体系中，我们利用Per-O-甲基化β-CD的惊人能力在水溶液中包合水溶性的四芳基卟啉，得到非常稳定的1：2(Por：Cd)包合物。[8]两个Per-O-甲基化的β-Cd部分通过一个吡啶配体桥联。用Lawrence等人报道的方法合成了1(方案1)。在pH 5.0的磷酸盐缓冲液中测量了[FeIII(TPPS)]的吸收光谱随1浓度的变化(图1)，以考察1是否形成了一个合适的络合物，其中的两个CD基团包括[M(TPPS)](M=金属离子)的5位和15位的磺基，以及吡啶配体与卟啉的MII或MIII位配位。[FeIII(H2O)2(TPPS)]与[FeIII(H2O)2(TPPS)]形成稳定的二水络合物[FeIII(H2O)2(TPPS)]。加入1后，[μ-(H2O)2(TPPS)]在388 nm处的Soret峰向421 nm移动，光谱变化急剧饱和，表明[FeIII(H2O)2(TPPS)]与[FeIII(H2O)2(TPPS)]之间形成了稳定的1：1络合物。
Herein we report reversible dioxygen binding to a simple model system of myoglobin composed of a per-O-methylated β-cyclodextrin (CD) dimer having a pyridine linker (1) and [tetrakis (4-sulfonatophenyl) porphinato] iron (ii)([FeII (tpps)]) in aqueous solution. Myoglobin (Mb) and hemoglobin (Hb) form stable O2 adducts in aqueous solution at a neutral pH value. Globin plays an essential role in stabilizing the O2 adduct in biological systems. Without this protein, oxyheme is immediately oxidized to a Met form by the action of a proton or hydroxide ion.[1] Heme is protected from acid-or base-induced autoxidation by the globin that surrounds the iron porphyrin (FePor). Many model systems of Mb and Hb were examined after the development of the picket-fence porphyrin by Collman et al.[2, 3] In most model systems O2 binding was achieved in organic solvents, where a trace amount of water had to be removed from the system. The concept proposed by Collman s research group has been expanded into the binding of O2 to hydrophobic picket-fence FeII porphyrins, which are included in vesicles [4] or albumin [5] in aqueous media. Although dendrimers with FeIIPor cores were expected to mimic the function of Mb or Hb, no stable O2 adducts were formed in these systems in aqueous solution.[6, 7] Since the O2 adduct of the dendrimers is efficiently formed in absolute toluene,[6] it is evident that construction of a hydrophobic pocket for placing the iron (ii) center of an FePor is the essential factor for realizing O2 binding in aqueous solution. In the present model system, we used the striking ability of per-O-methylated β-CD to include water-soluble tetraarylporphyrins and yield extremely stable 1: 2 (Por: CD) inclusion complexes in aqueous solution.[8] Two per-O-methylated β-CD moieties were linked by a bridge involving a pyridine ligand. Such a CD dimer (1) worked well as a simple Mb model in aqueous solution.The synthesis of 1 (Scheme 1) was carried out by using the method reported by Lawrence et al.[9] The changes in the absorption spectrum of [FeIII (tpps)] in phosphate buffer of pH 5.0 were measured as a function of the concentration of 1 (Figure 1) to examine whether 1 forms a suitable complex in which two CD moieties include the sulfonatophenyl groups at the 5 and 15 positions of [M (tpps)](M= metal ion) and the pyridine ligand coordinates to the MII or MIII site of the porphyrin. No μ-oxo dimer was formed at pH 5.0 and the predominant species involving [FeIII (tpps)] was the diaqua complex [FeIII (H2O) 2 (tpps)].[10] The Soret band of [FeIII-(H2O) 2 (tpps)] at 388 nm shifted to 421 nm upon addition of 1. The spectral changes were sharply saturated after the addition of one equivalent of 1, which indicated the formation of a very stable 1: 1 complex between [FeIII (H2O) 2 (tpps)] and 1. Analysis of the titration curve provided a binding constant