Izzet Guillaume, Douziech Bénédicte, Prangé Thierry, Tomas Alain, Jabin Ivan, Le Mest Yves, Reinaud Olivia
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Unité Mixte de Recherche Centre National de la Recherche Scientifique 8601, Université René Descartes, 45 Rue des Saints-Pères, 75270 Paris Cedex 06, France.
Proc Natl Acad Sci U S A. 2005 May 10;102(19):6831-6. doi: 10.1073/pnas.0500240102. Epub 2005 May 2.
Mono-copper enzymes play an important role in biology and their functionality is based on Cu(II)/Cu(I) redox processes. Modeling a mono-nuclear site remains a challenge for a better understanding of its intrinsic reactivity. The first member of a third generation of calixarene-based mono-copper "funnel" complexes is described. The ligand is a calix[6]arene capped by a tren unit, hence presenting a N(4) coordination site confined in a cavity. Its Cu(II) complexes were characterized by electronic and EPR spectroscopies. The x-ray structure of one of them shows a five-coordinated metal ion in a slightly distorted trigonal bipyramidal geometry thanks to its coordination to a guest ligand L (ethanol). The latter sits in the heart of the hydrophobic calixarene cone that mimics the active site chamber and the hydrophobic access channel of enzymes. Competitive binding experiments showed a preference order dimethylformamide > ethanol > MeCN for L binding at the single exchangeable metal site. Cyclic voltammetry studies showed irreversible redox processes in CH(2)Cl(2) when L is an oxygen donor caused by the redox-driven ejection of the guest at the Cu(I) level. In the presence of MeCN, a pseudoreversible process was obtained, owing to a fast equilibrium between a four and a five-coordinate Cu(I) species. Finally, a redox-driven ligand interchange of dimethylformamide for MeCN at the Cu(I) state allowed the trapping of the thermodynamically less stable Cu(II)-MeCN adduct. Hence, this work represents an important step toward the elaboration of a functional supramolecular model for redox mono-copper enzymes, named redox calix-zymes.
单核铜酶在生物学中发挥着重要作用，其功能基于Cu(II)/Cu(I)氧化还原过程。构建单核位点模型对于更好地理解其固有反应性仍然是一项挑战。本文描述了基于杯芳烃的第三代单核铜“漏斗”配合物的首个成员。配体是由三乙撑四胺单元封端的杯[6]芳烃，因此呈现出一个限制在腔内的N(4)配位位点。其Cu(II)配合物通过电子光谱和电子顺磁共振光谱进行了表征。其中一个配合物的X射线结构显示，由于其与客体配体L（乙醇）配位，金属离子呈五配位，处于轻微扭曲的三角双锥几何构型。后者位于疏水杯芳烃锥的中心，该锥模拟了酶的活性位点腔和疏水通道。竞争性结合实验表明，在单一可交换金属位点上，L的结合偏好顺序为二甲基甲酰胺>乙醇>乙腈。循环伏安法研究表明，当L是氧供体时，在CH₂Cl₂中会发生不可逆的氧化还原过程，这是由于在Cu(I)水平上客体的氧化还原驱动排出所致。在乙腈存在下，由于四配位和五配位Cu(I)物种之间的快速平衡，获得了一个准可逆过程。最后，在Cu(I)状态下，二甲基甲酰胺与乙腈之间的氧化还原驱动配体交换使得热力学上较不稳定的Cu(II)-乙腈加合物得以捕获。因此，这项工作朝着构建一种用于氧化还原单核铜酶的功能性超分子模型（称为氧化还原杯酶）迈出了重要一步。
