Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR CNRS 8601, Université Paris Descartes, Sorbonne Paris Cité, 45 rue des Saints Pères, 75006 Paris, France.
Chem Soc Rev. 2015 Jan 21;44(2):467-89. doi: 10.1039/c4cs00211c.
The design of biomimetic complexes for the modeling of metallo-enzyme active sites is a fruitful strategy for obtaining fundamental information and a better understanding of the molecular mechanisms at work in Nature's chemistry. The classical strategy for modeling metallo-sites relies on the synthesis of metal complexes with polydentate ligands that mimic the coordination environment encountered in the natural systems. However, it is well recognized that metal ion embedment in the proteic cavity has key roles not only in the recognition events but also in generating transient species and directing their reactivity. Hence, this review focuses on an important aspect common to enzymes, which is the presence of a pocket surrounding the metal ion reactive sites. Through selected examples, the following points are stressed: (i) the design of biomimetic cavity-based complexes, (ii) their corresponding host-guest chemistry, with a special focus on problems related to orientation and exchange mechanisms of the ligand within the host, (iii) cavity effects on the metal ion binding properties, including 1st, 2nd, and 3rd coordination spheres and hydrophobic effects and finally (iv) the impact these factors have on the reactivity of embedded metal ions. Important perspectives lie in the use of this knowledge for the development of selective and sensitive probes, new reactions, and green and efficient catalysts with bio-inspired systems.
仿生配合物设计用于模拟金属酶活性位点是获取关于自然界化学中分子机制基本信息和深入理解的一种富有成效的策略。模拟金属位点的经典策略依赖于合成具有多齿配体的金属配合物，这些配体模拟了在天然体系中遇到的配位环境。然而，人们已经充分认识到，金属离子嵌入蛋白质腔中不仅在识别事件中而且在生成瞬态物种和指导其反应性方面起着关键作用。因此，这篇综述重点关注了酶的一个共同的重要方面，即存在围绕金属离子反应位点的口袋。通过选择的例子，强调了以下几点：（i）基于仿生腔的配合物的设计，（ii）它们相应的主客体化学，特别关注配体在主体内的取向和交换机制相关的问题，（iii）腔对金属离子结合性质的影响，包括第一、第二和第三配位球以及疏水性效应，最后（iv）这些因素对嵌入金属离子反应性的影响。重要的前景在于将这些知识用于开发选择性和灵敏的探针、新反应以及具有生物启发系统的绿色高效催化剂。
