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100 years of metal coordination chemistry: from Alfred Werner to anticancer metallodrugs
Barry, Nicolas P.E. ; Sadler, P.J.
Barry, Nicolas P.E.
Sadler, P.J.
Publication Date
2014-12
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© 2014 De Gruyter. Reproduced in accordance with the publisher's self-archiving policy.
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Abstract
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 (RuII, OsII, RhIII, IrIII, PtII, PtIV).
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Barry NPE and Sadler PJ (2014) 100 years of metal coordination chemistry: from Alfred Werner to anticancer metallodrugs. Pure and Applied Chemistry. 86(12): 1897-1910.
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