§Laboratoire de Chimie, Electrochimie Moléculaires et Chimie Analytique, CNRS UMR 6521, Université de Bretagne Occidentale, 6 Avenue Le Gorgeu, 29238 Brest, France.
‡Laboratoire de Chimie Organique, Université Libre de Bruxelles (ULB), Avenue F. Roosevelt 50, CP160/06, B-1050 Brussels, Belgium.
Acc Chem Res. 2015 Jul 21;48(7):2097-106. doi: 10.1021/acs.accounts.5b00152. Epub 2015 Jun 23.
Supramolecular bioinorganic chemistry is a natural evolution in biomimetic metallic systems since it constitutes a further degree of complexity in modeling. The traditional approach consisting of mimicking the first coordination sphere of metal sites proved to be very efficient, because valuable data are extracted from these examples to gain insight in natural systems mechanisms. But it does not reproduce several specific aspects of enzymes that can be mimicked by the implementation of a cavity embedding the labile active site and thus controlling the properties of the metal ion by noncovalent interactions. This Account reports on a strategy aimed at reproducing some supramolecular aspects encountered in the natural systems. The cavity complexes described herein display a coordination site constructed on a macrocycle. Thanks to a careful design of the cavity-based ligands, complexes orienting their labile site specifically toward the inside of the macrocycle were obtained. The supramolecular systems are based on the flexible calix[6]arene core that surrounds the metal ion labile site, thereby constraining exogenous molecules to pass through the conic funnel to reach the metal center. Such an architecture confers to the metal ion very unusual properties and behaviors, which in many aspects are biologically relevant. Three generations of calix[6]-based ligands are presented and discussed in the context of modeling the monocopper sites encountered in some enzymes. A wide range of phenomena are highlighted such as the impact that the size and shape of the access channel to the metal center have on the selectivity and rate of the binding process, the possible remote control of the electronics through small modifications operated on the cavity edges, induced-fit behavior associated with host-guest association (shoe-tree effect) that affects the redox properties of the metal ion and the electron exchange pathway, consequences of forbidden associative ligand exchange allowing a redox switch to drive an "antithermodynamic" ligand exchange, drastic effects of the full control of the second coordination sphere, and dioxygen activation in a confined chamber conducted to a selective and unusual four-electron redox process. All these findings bring new clues for better understanding the control exerted by the proteic environment on a metal center, allow the identification of new reaction pathways, and lead to new proposals for enzymatic catalytic cycle (such as the formation of an alkylhydroperoxide intermediate for mononuclear Cu-hydroxylases). The supramolecular systems may also be exploited for designing highly selective and sensitive probes for molecules of particular function and shape or to design new selective catalysts.
超分子生物无机化学是仿生金属体系中的自然发展，因为它构成了模型复杂性的进一步程度。传统的方法包括模拟金属位点的第一配位球，被证明是非常有效的，因为从这些例子中提取有价值的数据可以深入了解自然体系的机制。但是，它不能复制酶的几个特定方面，这些方面可以通过实现嵌入不稳定活性位点的空腔来模拟，从而通过非共价相互作用控制金属离子的性质。本报告介绍了一种旨在复制自然体系中遇到的某些超分子方面的策略。本文所述的空腔配合物显示出构建在大环上的配位位点。通过精心设计基于空腔的配体，获得了将其不稳定位点定向特定朝向大环内部的配合物。超分子体系基于灵活的杯[6]芳烃核，该核包围金属离子不稳定位点，从而将外源分子限制在通过锥形漏斗到达金属中心。这种结构赋予金属离子非常不寻常的性质和行为，在许多方面与生物学相关。介绍并讨论了三代基于杯[6]的配体，以模拟某些酶中遇到的单铜位点。突出了各种现象，例如进入金属中心的通道的大小和形状对结合过程的选择性和速率的影响，通过对空腔边缘进行微小修改可能实现的电子远程控制，与主体-客体缔合相关的诱导配合行为（鞋树效应），这会影响金属离子的氧化还原性质和电子交换途径，禁止缔合配体交换的后果允许氧化还原开关驱动“反热力学”配体交换，完全控制第二配位球的巨大影响，以及在受限腔中激活氧气，导致选择性和不寻常的四电子氧化还原过程。所有这些发现都为更好地理解蛋白质环境对金属中心的控制提供了新的线索，确定了新的反应途径，并为酶催化循环提出了新的建议（例如，单核 Cu-羟化酶中形成烷基过氧化物中间体）。超分子体系也可用于设计对特定功能和形状的分子具有高选择性和敏感性的探针，或设计新的选择性催化剂。
