"Hangman" porphyrins for the assembly of a model heme water channel
"Hangman" porphyrins for the assembly of a model heme water channel
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DOI：
10.1021/ja003245k
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发表时间：
2001-02-21
影响因子：
15
通讯作者：
Nocera, DG
中科院分区：
文献类型：
--
作者：
Yeh, CY;Chang, CJ;Nocera, DG
血红素单位是自然界中发现的最普遍和最广泛的辅助因子之一1,2血红素依赖酶所表现出的令人惊讶的多种反应性（如O2运输和储存，3,4单外球电子转移，5代谢氧化反应6,7和O2还原8,9）是由围绕活性位点卟啉核心的折叠蛋白质的三级结构施加的微环境中微妙而精确的变化所控制的。在许多情况下，这种精细的控制是由氢键等非共价相互作用施加的；细胞色素P450酶提供了示例性系统。该单加氧酶家族的晶体学研究证明了溶剂内部水通道的存在，这些通道可以精细地调节血红素电子结构和氧化还原电位，并在多电子催化过程中提供可能的质子传递途径。然而，对于合成化学家来说，在生物环境之外为这种复杂的非共价聚集体构建结构和功能模型的挑战是一项艰巨的任务。在本文中，我们介绍了由卟啉和远端氢键基团以共面方式锚定在刚性间隔物上的新颖的极简血红素/水通道模型。这些柱状的“Hangman”卟啉具有独特的能力，可以通过固态和溶液中的氢键以受控的方式定向外源水，并提供单晶x射线分析表征的单体氢氧化铁卟啉。我们对小分子的质子偶联活化24,25的兴趣使我们最近开发了基于二苯并呋喃（DPD） 26和杂蒽（DPX） 27间隔剂的新型对称共面双卟啉的简便组装方法，这些间隔剂具有可变的口袋大小和最小的横向位移。类似的方法可用于产生不对称共面结构，其中刚性的杂蒽支架用于将氢键功能“悬挂”在卟啉大环（HPX）悬挂的卟啉杂蒽上，方案1)。在标准林赛条件下通过混合醛缩合合成卟啉H2-(HPX-CO2H)(1)。28,29羧酸配合物提供了接触多种官能团的途径；例如，酯和酰胺衍生物很容易由1制备。2与1金属化，然后碱性处理，得到相应的单体铁(III)-氢氧化物配合物Fe-OH (HPX-CO2H) 2。两侧的甲酰基提供的立体支撑阻止了双铁(III) μ-氧二聚体的形成。18, 30-32 2的1H NMR符合其氢氧化物的分子式；β-吡咯共振的下场化学位移（80.79,82.40 ppm）表明是单体高自旋Fe （III）卟啉。单晶x射线分析证实了2的结构（图1）；许多值得注意的特性值得在这里讨论。据我们所知，我们不知道单体氢氧化铁卟啉的另一种晶体结构。33此外，有趣的是，氢键网络促进轴向氢氧根配体选择性结合到HPX平台的远端。配合物呈扭曲的方锥体几何形状，五坐标Fe从N4平面上移出0.4947 Å， Fe- npyrrole平均键长为2.075 Å。Fe- oh - oh键长度为1.868 Å，比Fe (III)-aqua的Fe- o键长度短
The heme unit is one of the most ubiquitous and versatile cofactors found in Nature. 1, 2 The amazingly diverse reactivities displayed by heme-dependent enzymes (eg, O2 transport and storage, 3, 4 single outer-sphere electron transfer, 5 metabolic oxidation reactions6, 7 and O2 reduction8, 9) are governed by subtle and precise changes in the microenvironments imposed by the tertiary structures of the folded proteins surrounding the active site porphyrinic cores. In many cases, this exquisite control is exerted by noncovalent interactions such as hydrogen bonding; an exemplary system is provided by the cytochrome P450 enzymes. 7 Crystallographic studies of this family of monooxygenases give evidence for the presence of internal solvent water channels that finely tune heme electronic structure and redox potential, as well as providing a possible proton-relay pathway during multielectron catalysis. 10-14 However, the challenge of constructing structural and functional models15-23 for such complex, noncovalent aggregates outside the biological milieu poses a daunting task for the synthetic chemist. In this communication, we introduce novel, minimalist heme/water channel models composed of porphyrins and distal hydrogen-bonding groups anchored in a cofacial manner to a rigid spacer. These pillared “Hangman” porphyrins have the distinct ability to orient exogenous water in a controlled fashion via hydrogen bonding in the solid state and in solution, as well as affording a monomeric iron (III) hydroxide porphyrin to be characterized by single-crystal X-ray analysis. Our interest in the proton-coupled activation of small molecules24, 25 has led us to recently develop methods for the facile assembly of new symmetric cofacial bisporphyrins based on dibenzofuran (DPD) 26 and xanthene (DPX) 27 spacers that exhibit variable pocket sizes with minimal lateral displacements. A similar approach may be used to produce asymmetric cofacial architectures in which the rigid xanthene scaffold is used to “hang” a hydrogen-bonding functionality over the porphyrin macrocycle (HPX) hanging porphyrin xanthene, Scheme 1). Porphyrin H2-(HPX-CO2H)(1) is synthesized via a mixed-aldehyde condensation under standard Lindsey conditions. 28, 29 The carboxylic acid complex provides access to a wide variety of functional groups; for example, ester and amide derivatives are readily prepared from 1. Metalation of 1 with FeBr2 followed by alkaline workup affords the corresponding monomeric iron (III)-hydroxide complex Fe-OH (HPX-CO2H) 2. The steric buttressing provided by the flanking mesityl groups precludes the formation of bisiron (III) μ-oxo dimers. 18, 30-32 The 1H NMR of 2 is consistent with its formulation as a hydroxide species; the downfield chemical shifts of the β-pyrrole resonances (80.79, 82.40 ppm) are indicative31 of a monomeric high-spin Fe (III) porphyrin. The structure of 2 is confirmed by single-crystal X-ray analysis (Figure 1); a number of notable features merit discussion here. To the best of our knowledge, we are unaware of another reported crystal structure of a monomeric iron (III) hydroxide porphyrin. 33 Furthermore, it is interesting to note that the hydrogen-bonding network promotes selective binding of the axial hydroxide ligand to the distal side of the HPX platform. The complex adopts a distorted square pyramidal geometry with the pentacoordinate Fe elevated 0.4947 Å out of the N4 plane and an average Fe-Npyrrole bond length of 2.075 Å. The Fe-Ohydroxide bond length of 1.868 Å is shorter than the Fe-O distances found for Fe (III)-aqua