100 years of metal coordination chemistry: from Alfred Werner to anticancer metallodrugs
100 years of metal coordination chemistry: from Alfred Werner to anticancer metallodrugs
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DOI：
10.1515/pac-2014-0504
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发表时间：
2014-12-01
影响因子：
1.8
通讯作者：
Sadler, Peter J.
中科院分区：
文献类型：
--
作者：
Barry, Nicolas P. E.;Sadler, Peter J.
一百多年前，阿尔弗雷德·维尔纳 (Alfred Werner) 荣获诺贝尔化学奖。我们简要回顾一下他工作的时代、他的同事以及他在实验室使用的设备。他的想法具有开创性：金属离子不仅具有一级价（“hauptvalenz”，现在的氧化态），而且还具有二级价，即配位数（“nebenvalenz”）。当时有些人拒绝接受这个想法，但他意识到他的新思维将开辟新的研究领域。确实如此。我们通过新兴的药用金属配位化学领域（金属基治疗和诊断剂的设计）来说明这一点。金属配合物的生物活性不仅与金属及其氧化态密切相关，还与配位配体的类型和数量以及配位几何形状密切相关。这为结构和电子多样性的药理学空间提供了丰富的平台。有必要控制配体取代反应的热力学（金属-配体键的强度）和动力学，以提供具有明确作用机制的复合物。外层相互作用也可以在目标识别中发挥重要作用。我们目前的兴趣主要集中在 Werner 非常熟悉的相对惰性的金属配合物（Ru-II、Os-II、Rh-III、Ir-III、Pt-II、Pt-IV）。
Alfred Werner was awarded the Nobel Prize in Chemistry just over 100 years ago. We recall briefly the era in which he was working, his co-workers, and the equipment he used in his laboratories. His ideas were ground breaking: not only does a metal ion have a primary valency ("hauptvalenz", now the oxidation state), but also a secondary valency, the coordination number ("nebenvalenz"). At that time some refused to accept this idea, but he realised that his new thinking would open up new areas of research. Indeed it did. We illustrate this for the emerging field of medicinal metal coordination chemistry, the design of metal-based therapeutic and diagnostic agents. The biological activity of metal complexes depends intimately not only on the metal and its oxidation state, but also on the type and number of coordinated ligands, and the coordination geometry. This provides a rich platform in pharmacological space for structural and electronic diversity. It is necessary to control both the thermodynamics (strengths of metal-ligand bonds) and kinetics of ligand substitution reactions to provide complexes with defined mechanisms of action. Outer-sphere interactions can also play a major role in target recognition. Our current interest is focussed especially on relatively inert metal complexes which were very familiar to Werner (Ru-II, Os-II, Rh-III, Ir-III, Pt-II, Pt-IV).